Author: "SEGUIN, Nathalie" - Searchworks@Jio Institute Digital Library Search Results

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1. Les enjeux du système éducatif et de la recherche en 100 fiches - De l'école à l'université

Author: Bernard Christophe, Bouvier d’Yvoire Jean, Bracco Laetitia, Burlot Pascal, Di Méo Nicolas, Duret-Cantiolet Agnès, Fol Michel, Hauchard Seguin Nathalie, Jaffre Adeline, Le Roux Joëlle, Millet Anne-Cécile, Remy Matthieu, Réguigne Bruno, Yigit Orhan, Bernard Christophe, Bouvier d’Yvoire Jean, Bracco Laetitia, Burlot Pascal, Di Méo Nicolas, Duret-Cantiolet Agnès, Fol Michel, Hauchard Seguin Nathalie, Jaffre Adeline, Le Roux Joëlle, Millet Anne-Cécile, Remy Matthieu, Réguigne Bruno, and Yigit Orhan
Published: 2020

2. Regional Policy Dialog in Latin America and the Caribbean: Challenges and Opportunities for Water-Based Adaptation to Climate Change: Elements for a Regional Agenda

Author: Maturano Rodríguez, Carlos, primary, Miralles-Wilhelm, Fernando, additional, Gutiérrez Gómez, Guillermo, additional, Cordero Vejar, Mario, additional, Aguilar Amilpa, Enrique, additional, Velázquez Holguín, Marco Antonio, additional, Rodríguez, Andrés, additional, Medina Laguna, Grisell, additional, Rodríguez Ramos, Katia Karina, additional, Resendiz, Patricia, additional, Rojas Hernández, Pamela Alejandra, additional, Pagnoccheschi, Bruno, additional, Carro de la Fuente, Adán, additional, Fuentes Nava, Estrellita Mireya, additional, Siller, Diana, additional, Arrese Luco, Juan Antonio, additional, Hinojosa Aguirre, José María, additional, Villón Bracamonte, Ricardo Alaín, additional, Mota, Erick, additional, Burgues, Irene, additional, Galan, Roberto, additional, Ballestero Vargas, Maureen, additional, Badillo Ibarra, Isabel, additional, Vendruscolo, Simone, additional, Sánchez, Juan Carlos, additional, Chabrel, Marie-Violaine, additional, Reyes Gaytán, Jorge Alberto, additional, Córdoba, Rocío, additional, Genta, José Luis, additional, Meza, Jorge, additional, Landa, Rosalva, additional, Loures, Flavia, additional, Rendón, Claudia, additional, López Pérez, Mario, additional, Arroyo, Víctor, additional, Murillo Licea, Daniel, additional, Martínez, Julia, additional, Soares, Denise, additional, Rendón Pimentel, Luis, additional, Magaña, Víctor, additional, Mora Portuguez, Jorge, additional, Hurtado Aguilar, Carlos Alberto, additional, Díaz, Víctor, additional, Soto, Sergio, additional, Lozano Torres, Sergio, additional, Barrios Ordóñez, J. Eugenio, additional, Rojas, Diana, additional, Hernández Díaz, Josué Isaac, additional, García Gómez, María Concepción, additional, Krause, Matthias, additional, Sánchez Pérez, Claudia Olivia, additional, Sánchez Ramos, Yerania, additional, Martínez Ruiz, José Luis, additional, Zuleta, Javier, additional, Rosazza Asin, Eddie, additional, Seguin, Nathalie, additional, and Manzano Camarillo, Mario, additional
Published: 2010
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3. Diálogo Regional de Política de América Latina y el Caribe: Retos y oportunidades en adaptación al cambio climático en materia de agua: Elementos para una agenda regional

Author: Gómez, Román, Herron, Colin, López Pérez, Mario, Miralles-Wilhelm, Fernando, Aguilar, Enrique, Arrese Luco, Juan Antonio, Arroyo, Víctor, Badillo Ibarra, Isabel, Ballestero Vargas, Maureen, Barrios Ordoñez, Eugenio, Burgues, Irene, Carro de la Fuente, Adán, Chabrel, Marie-Violaine, Lozano Torres, Sergio, Córdoba, Rocío, Díaz, Víctor, Cordero Vejar, Mario, Fuentes Nava, Estrellita Mireya, Galan, Roberto, García Gómez, María Concepción, Genta, José Luis, Gutiérrez Gómez, Guillermo, Hernández Díaz, Josué Isaac, Hinojosa Aguirre, José María, Hurtado Aguilar, Carlos Alberto, Krause, Matthias, Landa, Rosalva, Loures, Flavia, Magaña, Víctor, Manzano Camarillo, Mario, Martínez, Julia, Martínez Ruiz, José Luis, Maturano Rodríguez, Carlos, Medina Laguna, Grisell, Meza, Jorge, Mora Portuguez, Jorge, Mota, Erick, Murillo Licea, Daniel, Pagnoccheschi, Bruno, Rendón, Claudia, Rendón Pimentel, Luis, Resendiz, Patricia, Reyes Gaytán, Jorge Alberto, Rodríguez, Andrés, Rodríguez Ramos, Katia Karina, Rojas, Diana, Rojas Hernández, Pamela Alejandra, Rosazza Asin, Eddie, Sánchez, Juan Carlos, Sánchez Pérez, Claudia Olivia, Sánchez Ramos, Yerania, Seguin, Nathalie, Siller, Diana, Soares, Denise, Soto, Sergio, Velázquez Holguín, Marco Antonio, Vendruscolo, Simone, Villón Bracamonte, Ricardo Alaín, Zuleta, Javier, Gómez, Román, Herron, Colin, López Pérez, Mario, Miralles-Wilhelm, Fernando, Aguilar, Enrique, Arrese Luco, Juan Antonio, Arroyo, Víctor, Badillo Ibarra, Isabel, Ballestero Vargas, Maureen, Barrios Ordoñez, Eugenio, Burgues, Irene, Carro de la Fuente, Adán, Chabrel, Marie-Violaine, Lozano Torres, Sergio, Córdoba, Rocío, Díaz, Víctor, Cordero Vejar, Mario, Fuentes Nava, Estrellita Mireya, Galan, Roberto, García Gómez, María Concepción, Genta, José Luis, Gutiérrez Gómez, Guillermo, Hernández Díaz, Josué Isaac, Hinojosa Aguirre, José María, Hurtado Aguilar, Carlos Alberto, Krause, Matthias, Landa, Rosalva, Loures, Flavia, Magaña, Víctor, Manzano Camarillo, Mario, Martínez, Julia, Martínez Ruiz, José Luis, Maturano Rodríguez, Carlos, Medina Laguna, Grisell, Meza, Jorge, Mora Portuguez, Jorge, Mota, Erick, Murillo Licea, Daniel, Pagnoccheschi, Bruno, Rendón, Claudia, Rendón Pimentel, Luis, Resendiz, Patricia, Reyes Gaytán, Jorge Alberto, Rodríguez, Andrés, Rodríguez Ramos, Katia Karina, Rojas, Diana, Rojas Hernández, Pamela Alejandra, Rosazza Asin, Eddie, Sánchez, Juan Carlos, Sánchez Pérez, Claudia Olivia, Sánchez Ramos, Yerania, Seguin, Nathalie, Siller, Diana, Soares, Denise, Soto, Sergio, Velázquez Holguín, Marco Antonio, Vendruscolo, Simone, Villón Bracamonte, Ricardo Alaín, and Zuleta, Javier
Abstract: El presente documento representa un esfuerzo coordinado entre varias instituciones y organizaciones de la región de América Latina y el Caribe por plasmar los resultados de una reflexión conjunta sobre el tema de la adaptación al cambio climático en la comunidad hídrica y en el marco de un Diálogo Regional de Política. El propósito principal de este Diálogo es el de dar a conocer una serie de mensajes claves y recomendaciones que permitan definir de manera informada las políticas públicas pertinentes y sus acciones correspondientes al cambio climático. Los resultados del Diálogo hasta el día de hoy se han plasmado en la presente versión del documento, que se presentará en el marco de los Diálogos por el Agua y el Cambio Climático, un evento asociado a la COP16 en Cancún, México., This document represents a coordinated effort among several institutions and organizations in the Latin America and the Caribbean region to present the results of a joint reflection on the issue of water-based adaptation to climate change as part of a Regional Policy Dialog process. The main purpose of this Dialog is to communicate to politicians and decision makers -both within the water community and from other public policy areas relevant to the topic- and other actors involved, a series of key messages and recommendations that enable them to define, in an informed manner, public policies and corresponding actions on climate change adaptation. The results of this dialog to date are reflected in this version of the document to be presented on December 3rd as part of the Dialogs for Water and Climate Change (D4WCC), an event associated with the COP16 to be held in Cancun, Mexico.
Published: 2011

4. Consumer reactions to product placement strategies in television sponsorship

Author: D'Astous, Alain and Seguin, Nathalie
Subjects: Advertising -- Methods, Consumer behavior -- Analysis, Corporate sponsorship -- Analysis, Advertising, marketing and public relations, Business, Business, general
Abstract: A factorial design model for consumer reactions was developed to assess the impact of product placement strategies on the marketing efficiency of television sponsorship programs. Experimental results derived from placement, sponsor, television program and program congruity factors suggest that the use of obtrusive product placement strategies tend to generate negative behavior among consumers. On the other hand, placement strategies that are highly related with sponsor programs draw positive and ethical consumer reactions.
Published: 1999

5. Delta opioid receptors on nociceptive sensory neurons mediate peripheral endogenous analgesia in colitis

Author: Xavier Mas-Orea, Lilian Basso, Catherine Blanpied, Claire Gaveriaux-Ruff, Nicolas Cenac, Gilles Dietrich, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INFINITy cellular imaging core facility, ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), SEGUIN, Nathalie, and Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID
Subjects: Immunology, T lymphocytes, Intestinal inflammation, Cellular and Molecular Neuroscience, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Receptors, Opioid, delta, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Intestinal Mucosa, RC346-429, Inflammation, Mice, Knockout, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Neuroscience, Research, Nociceptors, Colitis, Opioids, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Disease Models, Animal, Opioid receptors, Neurology, Visceral pain, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neurology. Diseases of the nervous system, Analgesia, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Inflammatory visceral pain is endogenously controlled by enkephalins locally released by mucosal CD4+ T lymphocytes in mice. The present study aimed at identifying opioid receptor(s) expressed on nociceptive sensory nerves involved in this peripheral opioid-mediated analgesia. Methods The peripheral analgesia associated with the accumulation of CD4+ T lymphocytes within the inflamed colonic mucosa was assessed in conditional knockout mice specifically deleted for either of the two opioid receptors for enkephalins (i.e., µ (MOR) and δ (DOR) receptors) in Nav1.8-expressing sensory neurons in the dextran sulfate sodium (DSS)-induced colitis model. Results Endogenous analgesia is lost in conditional knockout mice for DOR, but not MOR at the later phase of the DSS-induced colitis. The absence of either of the opioid receptors on sensory nerves had no impact on both the colitis severity and the rate of T lymphocytes infiltrating the inflamed colonic mucosa. Conclusion The key role of DOR on primary afferents in relieving intestinal inflammatory pain opens new therapeutic opportunities for peripherally restricted DOR analgesics to avoid most of the side effects associated with MOR-targeting drugs used in intestinal disorders.
Published: 2022

6. Age and spatio-temporal variations in food resources modulate stress-immunity relationships in three populations of wild roe deer

Author: Jeffrey Carbillet, Marine Hollain, Benjamin Rey, Rupert Palme, Maryline Pellerin, Corinne Regis, Anne Geffré, Jeanne Duhayer, Sylvia Pardonnet, François Debias, Joël Merlet, Jean-François Lemaître, Hélène Verheyden, Emmanuelle Gilot-Fromont, Unité de recherche Comportement et Ecologie de la Faune Sauvage (CEFS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LTSER ZA PYRenees GARonne, Centre National de la Recherche Scientifique (CNRS), Institute of Ecology and Earth Sciences [Tartu], University of Tartu, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Office français de la biodiversité (OFB), University of Veterinary Medicine [Vienna] (Vetmeduni), Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), The study was funded by INRAE, VetAgro Sup and ONCFS/OFB, ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), SEGUIN, Nathalie, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, and PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID
Subjects: Innate immunity, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Hydrocortisone, Deer, Ecophysiology, Stress hormones, Adaptive immunity, Animals, Wild, Trade-off, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Animals, Faecal glucocorticoid metabolites, [SDV.BA.ZV] Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Animal Science and Zoology, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Glucocorticoids, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Living in variable and unpredictable environments, organisms face recurrent stressful situations. The endocrine stress response, which includes the secretion of glucocorticoids, helps organisms to cope with these perturbations. Although short-term elevations of glucocorticoid levels are often associated with immediate beneficial consequences for individuals, long-term glucocorticoid elevation can compromise key physiological functions such as immunity. While laboratory works highlighted the immunosuppressive effect of long-term elevated glucocorticoids, it remains largely unknown, especially in wild animals, whether this relationship is modulated by individual and environmental characteristics. In this study, we explored the co-variation between baseline cortisol levels, assessed non-invasively using faecal cortisol metabolites (FCMs), and 12 constitutive indices of innate, inflammatory, and adaptive immune functions, in wild roe deer living in three populations with contrasting environmental conditions. Using longitudinal data on 564 individuals, we further investigated whether age and spatio-temporal variations in the quantity and quality of food resources affect the relationship between FCMs and immunity. Negative covariation with glucocorticoids was evident only for innate and inflammatory markers of immunity, while adaptive immunity appeared to be positively or not linked to glucocorticoids. In addition, the negative covariations were generally exacerbated, or revealed, in individuals facing harsh environmental constraints and in old individuals. Therefore, our results highlight the importance of measuring multiple immune markers of immunity in individuals from contrasted environments to unravel the complex relationships between glucocorticoids and immunity in wild animals. Our results also help explain conflicting results found in the literature and could improve our understanding of the long-term consequences of elevated glucocorticoid levels on disease spread and population dynamics.
Published: 2023

7. Boot camp approach to surgical residency preparation: feedback from a French university hospital

Author: Etienne Buscail, Fabrice Muscari, Aurélien Hostalrich, Manon Bolzinger, Sandra Malavaud, Vincent Minville, Charlotte Martin, Magali Delhoste, Charles Henri Houze-Cerfon, Simon Buscail, Bruno Bastiani, Mathieu Roumiguié, Ariane Weyl, Nicolas Carrère, Olivier Abbo, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), The Toulouse Bar Association, Toulouse Institute for Health Stimulation, and SEGUIN, Nathalie
Subjects: Male, Medical student education, Preparedness surgical residency, [SHS.STAT]Humanities and Social Sciences/Methods and statistics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Students, Medical, Surgical skills, [SHS.EDU]Humanities and Social Sciences/Education, [SHS.EDU] Humanities and Social Sciences/Education, Surgical residency program in France, Internship and Residency, General Medicine, Curriculum design, Feedback, Education, Hospitals, University, Video-based learning, [SHS.STAT] Humanities and Social Sciences/Methods and statistics, Humans, Surgery, Female, Educational Measurement, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction The transition from medical student to surgical resident is not a simple one. The aim of this study was to report the experience of a university hospital in the organization of the induction course for future surgical residents and the contribution of a video support in the learning of the suture. Material and method We were able to study two consecutive years of students (October 2020 and 2021). Concerning the practical and technical workshops (learning suture) we carried out a comparative study between two groups of students. A group that had video support for learning suture (video group) and a group without video (control group). The evaluation of the suture was performed in a blinded manner by two supervising surgeons. The other practical workshop was drain fixation; the students did not have a video for this workshop. A comparative study was also performed for the drain fixation workshop between the two groups (video group and control group). A program of theoretical courses was also set up. This program is established according to the different future functions of the residents by integrating medico-legal notions and teamwork. Satisfaction questionnaires were given to the students and the answers were given two months after taking up their duties in the hospital (6 questions with Likert scale and 4 free questions). Results The cohort consisted of 58 students (29 each in 2020 and 29 in 2021). Comparative analyses of the evaluation of the suture workshops showed better performance in the video group compared with the group without video. The comparison of these two groups did not show significant differences in the drain fixation workshop. The theoretical teaching was broken down according to the students' future tasks and each speaker was a specialist in his or her field of expertise. The results of the questionnaires showed a desire on the part of the students to increase the time spent on practical workshops and theoretical forensic teaching. Conclusion We were able to show through these two years of a program that we were able to offer a surgical resident preparation course. In addition, we have highlighted the contribution of a video support in the learning curve of the suture.
Published: 2022

8. P06-15 Exposure to a complex and human-relevant mixture of eight environmental toxicants during folliculogenesis alters ovarian follicular populations in the young adult female rabbit

Author: S. El Fouikar, N. Van Acker, V. Helies, F.-X. Frenois, A. Alloy, F. Giton, R. Léandri, N. Gatimel, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), SEGUIN, Nathalie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Toulouse [Toulouse]
Subjects: [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BA.ZV] Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, General Medicine, Toxicology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology
Abstract: International audience
Published: 2022

9. Rhizobium leguminosarum symbiovar viciae strains are natural wheat endophytes that can stimulate root development

Author: Claudia Bartoli, Stéphane Boivin, Marta Marchetti, Carine Gris, Virginie Gasciolli, Mégane Gaston, Marie‐Christine Auriac, Frédéric Debellé, Ludovic Cottret, Aurélien Carlier, Catherine Masson‐Boivin, Marc Lepetit, Benoit Lefebvre, Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Université de Rennes (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire des Interactions Plantes Microbes Environnement (LIPME), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Plateforme TRI FR-AIB, Fédération de Recherche Agrobiosciences, Interactions et Biodiversité (FR AIB), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Sophia Agrobiotech (ISA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Côte d'Azur (UCA), INRAE Department of Plant Health and Environment (SPE), IDEX UNITI, Grant/Award Number: RHIZOWHEAT, ANR-18-EURE-0019,TULIP-GSR,The Toulouse-Perpignan(2018), ANR-10-LABX-0041,TULIP,Towards a Unified theory of biotic Interactions: the roLe of environmental(2010), ANR-16-CE20-0021,GRaSP,Caractérisation du déterminisme génétique du choix du partenaire symbiotique pour une amélioration de la symbiose fixatrice d'azote chez le pois(2016), ANR-16-CE20-0025,WHEATSYM,ROLES DES SIGNAUX MICROBIENS LCO/CO ET DE LEURS RECEPTEURS DE PLANTES DANS DES INTERACTIONS BENEFIQUES ENTRE MONOCOTYLEDONES ET MICROORGANISMES DU SOL(2016), SEGUIN, Nathalie, The Toulouse-Perpignan - - TULIP-GSR2018 - ANR-18-EURE-0019 - EURE - VALID, Towards a Unified theory of biotic Interactions: the roLe of environmental - - TULIP2010 - ANR-10-LABX-0041 - LABX - VALID, Caractérisation du déterminisme génétique du choix du partenaire symbiotique pour une amélioration de la symbiose fixatrice d'azote chez le pois - - GRaSP2016 - ANR-16-CE20-0021 - AAPG2016 - VALID, ROLES DES SIGNAUX MICROBIENS LCO/CO ET DE LEURS RECEPTEURS DE PLANTES DANS DES INTERACTIONS BENEFIQUES ENTRE MONOCOTYLEDONES ET MICROORGANISMES DU SOL - - WHEATSYM2016 - ANR-16-CE20-0025 - AAPG2016 - VALID, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, [SDV.SA] Life Sciences [q-bio]/Agricultural sciences, Rhizobium leguminosarum, Bacteria, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, Microbiology, [SDV.BV.BOT] Life Sciences [q-bio]/Vegetal Biology/Botanics, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Endophytes, Symbiosis, Root Nodules, Plant, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Ecology, Evolution, Behavior and Systematics, Triticum, Phylogeny, Rhizobium
Abstract: International audience; Although rhizobia that establish a nitrogen-fixing symbiosis with legumes are also known to promote growth in non-legumes, studies on rhizobial associations with wheat roots are scarce. We searched for Rhizobium leguminosarum symbiovar viciae (Rlv) strains naturally competent to endophytically colonize wheat roots. We isolated 20 strains from surface-sterilized wheat roots and found a low diversity of Rlv compared to that observed in the Rlv species complex. We tested the ability of a subset of these Rlv for wheat root colonization when co-inoculated with other Rlv. Only a few strains, including those isolated from wheat roots, and one strain isolated from pea nodules, were efficient in colonizing roots in co-inoculation conditions, while all the strains tested in single strain inoculation conditions were found to colonize the surface and interior of roots. Furthermore, Rlv strains isolated from wheat roots were able to stimulate root development and early arbuscular mycorrhizal fungi colonization. These responses were strain and host genotype dependent. Our results suggest that wheat can be an alternative host for Rlv; nevertheless, there is a strong competition between Rlv strains for wheat root colonization. In addition, we showed that Rlv are endophytic wheat root bacteria with potential ability to modify wheat development.
Published: 2022

10. Co-Infection and Ventilator-Associated Pneumonia in Critically Ill COVID-19 Patients Requiring Mechanical Ventilation: A Retrospective Cohort Study

Author: Benjamine Sarton, Marion Grare, Fanny Vardon-Bounes, Anna Gaubert, Stein Silva, Laure Crognier, Béatrice Riu, Thierry Seguin, Bernard Georges, Vincent Minville, Stéphanie Ruiz, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Anesthésie Réanimation [CHU de Toulouse], and SEGUIN, Nathalie
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, COVID-19, Medicine (miscellaneous), intensive care unit, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, General Biochemistry, Genetics and Molecular Biology, ventilator-associated pneumonia, co-infection, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, influenza, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, H1N1
Abstract: International audience; Considering virus-related and drug-induced immunocompromised status of critically ill COVID-19 patients, we hypothesize that these patients would more frequently develop ventilator-associated pneumonia (VAP) than patients with ARDS from other viral causes. We conducted a retrospective observational study in two intensive care units (ICUs) from France, between 2017 and 2020. We compared bacterial co-infection at ICU admission and throughout the disease course of two retrospective longitudinally sampled groups of critically ill patients, who were admitted to ICU for either H1N1 or SARS-CoV-2 respiratory infection and depicted moderate-to-severe ARDS criteria upon admission. Sixty patients in the H1N1 group and 65 in the COVID-19 group were included in the study. Bacterial co-infection at the endotracheal intubation time was diagnosed in 33% of H1N1 and 16% COVID-19 patients (p = 0.08). The VAP incidence per 100 days of mechanical ventilation was 3.4 (2.2–5.2) in the H1N1 group and 7.2 (5.3–9.6) in the COVID-19 group (p < 0.004). The HR to develop VAP was of 2.33 (1.34–4.04) higher in the COVID-19 group (p = 0.002). Ten percent of H1N1 patients and 30% of the COVID-19 patients had a second episode of VAP (p = 0.013). COVID-19 patients have fewer bacterial co-infections upon admission, but the incidence of secondary infections increased faster in this group compared to H1N1 patients.
Published: 2022

11. Role of milk and milk products in the spread of methicillin-resistant Staphylococcus aureus in the dairy production chain

Author: Yacine Titouche, Madjid Akkou, Karim Houali, Frédéric Auvray, Jacques‐Antoine Hennekinne, Université Mouloud Mammeri [Tizi Ouzou] (UMMTO), Université Saâd Dahlab Blida 1 (UB1), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de sécurité des aliments de Maisons-Alfort (LSAl), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratory for Food Safety, ANSES, and SEGUIN, Nathalie
Subjects: Methicillin-Resistant Staphylococcus aureus, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Microbial Sensitivity Tests, Staphylococcal Infections, milk products, pheno, milkmilk contamination, Anti-Bacterial Agents, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Milk, [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Animals, Humans, genotypic characteristics, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: International audience; Milk and milk products can harbor a multiple varieties of microorganisms. Therefore, they can be an important source of foodborne pathogens, including multidrug-resistant bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide spectrum of infections both in animals and humans. Over the last two decades, the presence of MRSA in foods and food-producing animals, including milk and milk products, has been frequently reported worldwide, raising public health concerns. In order to monitor and prevent foodborne MRSA contamination, it is necessary to understand their sources, the pheno/genotypic characteristics of the strains, and their transmission dynamics. In this review, studies conducted worldwide were summarized in order to assess the prevalence and diversity of MRSA circulating in milk and milk products. The risk factors for the occurrence of MRSA in milk and milk products were also discussed with preventive and control measures to avoid MRSA contamination in the dairy food chain.
Published: 2022

12. Odours of cancerous mouse congeners: detection and attractiveness

Author: Flora Gouzerh, Bruno Buatois, Maxime R. Hervé, Maicol Mancini, Antonio Maraver, Laurent Dormont, Frédéric Thomas, Guila Ganem, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Université de Rennes (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherches Ecologiques et Evolutives sur le Cancer (MIVEGEC-CREEC), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), University of Montpellier, MAVA Foundation, MIVEGEC: Maladies Infectieuses et Vecteurs Ecologie Genetique Evolution et Controle, ANR-18-CE35-0009,TRANSCAN,ECOLOGIE ET EVOLUTION DES CANCERS TRANSMISSIBLES(2018), SEGUIN, Nathalie, APPEL À PROJETS GÉNÉRIQUE 2018 - ECOLOGIE ET EVOLUTION DES CANCERS TRANSMISSIBLES - - TRANSCAN2018 - ANR-18-CE35-0009 - AAPG2018 - VALID, Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE)
Subjects: Male, Mus musculus domesticus, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, EGFR oncogenic mutation, Body odours, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, General Biochemistry, Genetics and Molecular Biology, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Mice, Female preference, Neoplasms, Odorants, Odour discrimination, Animals, Female, Volatile organic compounds, Lung cancer, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, General Agricultural and Biological Sciences, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Chemical communication plays a major role in social interactions. Cancer, by inducing changes in body odours, may alter interactions between individuals. In the framework of research targeting non-invasive methods to detect early stages of cancer development, this study asked whether untrained mice could detect odour changes in cancerous congeners. If yes, were they able to detect cancer at an early developmental stage? Did it influence female preference? Did variations in volatile organic components of the odour source paralleled mice behavioural responses? We used transgenic mice strains developing or not lung cancer upon antibiotic ingestion. We sampled soiled bedding of cancerous mice (CC) and not cancerous mice (NC), at three experimental conditions: before (T0), early stage (T2) and late stage (T12) of cancer development. Habituation/generalisation and two-way preference tests were performed where soiled beddings of CC and NC mice were presented to wild-derived mice. The composition and relative concentration of volatile organic components (VOC) in the two stimuli types were analysed. Females did not show directional preference at any of the experimental conditions, suggesting that cancer did not influence their choice behaviour. Males did not discriminate between CC and NC stimuli at T0 but did so at T2 and T12, indicating that wild-derived mice could detect cancer at an early stage of development. Finally, although the VOC bouquet differed between CC and NC it did not seem to parallel the observed behavioural response suggesting that other types of odorant components might be involved in behavioural discrimination between CC and NC mice.
Published: 2022

13. Outer membrane vesicles produced by pathogenic strains of Escherichia coli block autophagic flux and exacerbate inflammasome activation

Author: Laure David, Frédéric Taieb, Marie Pénary, Pierre-Jean Bordignon, Rémi Planès, Salimata Bagayoko, Valérie Duplan-Eche, Etienne Meunier, Eric Oswald, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INCa-Canceropole GSO, European Project: 804249,INFLAME, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), SEGUIN, Nathalie, and Deciphering the host and microbial grounds that license inflammasome-mediated execution - INFLAME - 804249 - INCOMING
Subjects: Autophagosome, Autolysosome, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, outer membrane vesicle, medicine.disease_cause, Microbiology, inflammasome, Lysosome, medicine, Autophagy, Escherichia coli, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, pathogenesis, Inflammasome, Hemolysin, Cell Biology, HlyF, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Bacterial outer membrane, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Escherichia coli strains are responsible for a majority of human extra-intestinal infections, resulting in huge direct medical and social costs. We had previously shown that HlyF encoded by a large virulence plasmid harbored by pathogenic E. coli is not a hemolysin but a cytoplasmic enzyme leading to the overproduction of outer membrane vesicles (OMVs). Here, we showed that these specific OMVs inhibit the macroautophagic/autophagic flux by impairing the autophagosome-lysosome fusion, thus preventing the formation of acidic autolysosomes and autophagosome clearance. Furthermore, HlyF-associated OMVs were more prone to activate the non-canonical inflammasome pathway. Because autophagy and inflammation are crucial in the host’s response to infection especially during sepsis, our findings revealed an unsuspected role of OMVs in the crosstalk between bacteria and their host, highlighting the fact that these extracellular vesicles have exacerbated pathogenic properties. Abbreviations: AIEC: adherent-invasive E. coliBDI: bright detail intensityBMDM: bone marrow‐derived macrophagesCASP: caspaseE. coli: Escherichia coliEHEC: enterohemorrhagic E. coliExPEC: extra-intestinal pathogenic E. coliGSDMD: gasdermin DGFP: green fluorescent proteinHBSS: Hanks’ balanced salt solutionHlyF: hemolysin FIL1B/IL‐1B: interleukin 1 betaISX: ImageStreamX systemLPS: lipopolysaccharideMut: mutatedOMV: outer membrane vesicleRFP: red fluorescent proteinTEM: transmission electron microscopyWT: wild-type
Published: 2022

14. Altered Subpopulations of Red Blood Cells and Post-treatment Anemia in Malaria

Author: Charlotte Chambrion, Mallorie Depond, Lucia Angella, Oussama Mouri, Eric Kendjo, Aurélie Fricot-Monsinjon, Camille Roussel, Sylvestre Biligui, Ilhame Tantaoui, Aida Taieb, Nicolas Argy, Sandrine Houzé, Renaud Piarroux, Jean-Yves Siriez, Stéphane Jaureguiberry, Sébastien Larréché, Marc Théllier, Nicolas Cenac, Pierre Buffet, Papa Alioune Ndour, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière] (CNRpalu), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Robert Debré Paris, Hôpital Robert Debré, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French Ministry of Research, GR-Ex laboratory of excellence, ANR-18-CE17-0018,PHeSMalEBiPPP,Anémie hémolytique post-traitement dans le paludisme grave: Elucidation de la clairance biomécanique des globules rouges pittés pour la prédiction et la prévention(2018), SEGUIN, Nathalie, and APPEL À PROJETS GÉNÉRIQUE 2018 - Anémie hémolytique post-traitement dans le paludisme grave: Elucidation de la clairance biomécanique des globules rouges pittés pour la prédiction et la prévention - - PHeSMalEBiPPP2018 - ANR-18-CE17-0018 - AAPG2018 - VALID
Subjects: membrane lipid balance, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Physiology, pitted or once infected RBC, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], artemisinin derivatives, falcipaprum, RBC deformability, spleen filtering funcion, Physiology (medical), malaria anemia, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: In acute malaria, the bulk of erythrocyte loss occurs after therapy, with a nadir of hemoglobin generally observed 3–7 days after treatment. The fine mechanisms leading to this early post-treatment anemia are still elusive. We explored pathological changes in RBC subpopulations by quantifying biochemical and mechanical alterations during severe malaria treated with artemisinin derivatives, a drug family that induce “pitting” in the spleen. In this study, the hemoglobin concentration dropped by 1.93 G/dl during therapy. During the same period, iRBC accounting for 6.12% of all RBC before therapy (BT) were replaced by pitted-RBC, accounting for 5.33% of RBC after therapy (AT). RBC loss was thus of 15.9%, of which only a minor part was due to the loss of iRBC or pitted-RBC. When comparing RBC BT and AT to normal controls, lipidomics revealed an increase in the cholesterol/phosphatidylethanolamine ratio (0.17 versus 0.24, p < 0.001) and cholesterol/phosphatidylinositol ratio (0.36 versus 0.67, p = 0.001). Using ektacytometry, we observed a reduced deformability of circulating RBC, similar BT and AT, compared to health control donors. The mean Elongation Index at 1.69Pa was 0.24 BT and 0.23 AT vs. 0.28 in controls (p < 0.0001). At 30Pa EI was 0.56 BT and 0.56 AT vs. 0.60 in controls (p < 0.001). The retention rate (rr) of RBC subpopulations in spleen-mimetic microsphere layers was higher for iRBC (rr = 20% p = 0.0033) and pitted-RBC (rr = 19%, p = 0.0031) than for healthy RBC (0.12%). Somewhat surprisingly, the post-treatment anemia in malaria results from the elimination of RBC that were never infected.
Published: 2022
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15. Rabbit targeted genomic sequences after heterologous hybridization using human exome

Author: Nathalie Iannuccelli, Julien Sarry, Yvon Billon, Patrick Aymard, Virginie Helies, Cédric Cabau, Cécile Donnadieu, Julie Demars, SEGUIN, Nathalie, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité Expérimentale Elevages Porcins Innovants (GenESI), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and INRAE Animal Genetics Department
Subjects: Mammals, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.BA] Life Sciences [q-bio]/Animal biology, Genotyping Techniques, [SDV.BA]Life Sciences [q-bio]/Animal biology, Targeted DNA sequencing, Capture, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, High-Throughput Nucleotide Sequencing, General Medicine, Rabbit, Heterologous hybridization, Exons, Genomics, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, Exome, Rabbits, Human
Abstract: Objective Causal mutations for major genes that underlie a broad range of morphological traits are often located within exons of genes that then affect protein functions. Non-model organism genetic studies are not easy to perform due to the lack of genome-wide molecular tools such as SNP genotyping array. Genotyping-By-Sequencing (GBS) methods offer an alternative. Consequently, we used this approach that is focused on the exome to target and identify major genes in rabbit populations. Data description We used a heterologous enrichment method before sequencing, allowing us to capture the rabbit exome using the marketed human panel since mammal protein coding genes are well conserved across the phylogenic tree of species. This targeted strategy was performed on 52 French rabbits from 5 different French strains (Californian, New-Zealand, Castor, Chinchilla and Laghmere). We generated 3.4 billion sequencing reads and approximately 29–140 million of reads per DNA sample. The expected exome coverage per sample ranged between 118 and 566X. The present dataset could be useful for the scientific community working on rabbit species in order to (i) improve the annotation of the rabbit reference genome Oryctolagus cuniculus (OryCun2.0), (ii) enrich the characterization of polymorphisms segregating in rabbits and (iii) evaluate the genetic biodiversity in different rabbit strains. Raw sequences were deposited in the European Nucleotide Archive (ENA) at the European Molecular Biology Laboratory- European Bioinformatics Institute (EMBL-EBI) data portal under bioproject accession number PRJEB37917.
Published: 2022

16. Cholesterol-rich naked mole-rat brain lipid membranes are susceptible to amyloid beta-induced damage in vitro

Author: Urriola-Munoz, Paulina, St John Smith, Ewan, Frankel, Daniel, Davies, Matthew, Bhushan, Bharat, Kulaberoglu, Yavuz, Urriola- Munoz, Paulina, Bertrand-Michel, Justine, Pergande, Melissa, Smith, Andrew, Preet, Swapan, Park, Thomas, Vendruscolo, Michele, Rankin, Kenneth, Cologna, Stephanie, Kumita, Janet, Cenac, Nicolas, St, Ewan, Smith, John, University of Cambridge [UK] (CAM), Newcastle University [Newcastle], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Illinois [Chicago] (UIC), University of Illinois System, Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), EPSRC Underpinning Multi-User Equipment Call : EP/P030467/1, National Science Foundation (NSF) : 1655494, UIC DFI Fellowship, Cancer Research UK/RCUK : C56829/A22053, Dunhill Medical Trust : RPGF2002\188, BBSRC-DTP studentship, Centre for Misfolding Diseases, ANR-18-CE14-0039,LiBacPain,Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable(2018), Vendruscolo, Michele [0000-0002-3616-1610], Kumita, Janet [0000-0002-3887-4964], Apollo - University of Cambridge Repository, SEGUIN, Nathalie, and APPEL À PROJETS GÉNÉRIQUE 2018 - Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable - - LiBacPain2018 - ANR-18-CE14-0039 - AAPG2018 - VALID
Subjects: Male, Aging, Amyloid beta, Liquid ordered phase, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], brain, Lipid Bilayers, Longevity, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Naked mole-rat, 03 medical and health sciences, 0302 clinical medicine, Species Specificity, Lipidomics, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Lipid bilayer, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Amyloid beta-Peptides, biology, Chemistry, Mole Rats, Cell Membrane, Neurotoxicity, neurodegeneration, Cell Biology, biology.organism_classification, medicine.disease, Peptide Fragments, amyloid beta, Mice, Inbred C57BL, Membrane, Cholesterol, biology.protein, Biophysics, lipids (amino acids, peptides, and proteins), Female, Sphingomyelin, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Paper
Abstract: Naked mole-rats are extraordinarily long-lived rodents that offer unique opportunities to study the molecular origins of age-related neurodegenerative diseases. Remarkably, they do not accumulate amyloid plaques, even though their brains contain high concentrations of amyloid beta (Aβ) peptide from a young age. Therefore, they represent a particularly favourable organism to study the mechanisms of resistance against Aβ neurotoxicity. Here we examine the composition, phase behaviour, and Aβ interactions of naked mole-rat brain lipids. Relative to mouse, naked mole-rat brain lipids are rich in cholesterol and contain sphingomyelin in lower amounts and of shorter chain lengths. Proteins associated with the metabolism of ceramides, sphingomyelins and sphingosine-1-phosphate receptor 1 were also found to be decreased in naked mole-rat brain lysates. Correspondingly, we find that naked mole-rat brain lipid membranes exhibit a high degree of phase separation, with the liquid ordered phase extending to 80% of the supported lipid bilayer. These observations are consistent with the 'membrane pacemaker' hypothesis of ageing, according to which long-living species have lipid membranes particularly resistant to oxidative damage. We also found that exposure to Aβ disrupts naked mole-rat brain lipid membranes significantly, breaking the membrane into pieces while mouse brain derived lipids remain largely intact upon Aβ exposure.
Published: 2020

17. Inhibition of ubiquitin-specific protease 7 sensitizes acute myeloid leukemia to chemotherapy

Author: Pierre-Luc Mouchel, Laure David, Jean-Emmanuel Sarry, Véronique Mansat-De Mas, Sarah Bertoli, Maëlle Cartel, Mathilde Gotanègre, Stéphane Manenti, Arnaud Besson, Christine Didier, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Équipe labellisée Ligue Nationale Contre le Cancer [Toulouse], Ligue Nationale Contre le Cancer [Paris] (LNCC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ligue nationale contre le cancer, SEGUIN, Nathalie, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Apoptosis, Mice, SCID, Ubiquitin-Specific Peptidase 7, Transcriptome, Mice, 0302 clinical medicine, Mice, Inbred NOD, hemic and lymphatic diseases, Tumor Cells, Cultured, RNA, Small Interfering, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Cytarabine, Myeloid leukemia, Hematology, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Survival Rate, Leukemia, Myeloid, Acute, Oncology, 030220 oncology & carcinogenesis, Female, Signal Transduction, Cell signalling, medicine.drug, Antimetabolites, Antineoplastic, Programmed cell death, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Acute myeloid leukaemia, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Animals, Humans, Cell Proliferation, Chemotherapy, business.industry, Cell growth, Gene Expression Profiling, Gene signature, Xenograft Model Antitumor Assays, 030104 developmental biology, Drug Resistance, Neoplasm, Cell culture, Cancer research, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Resistance of acute myeloid leukemia (AML) to therapeutic agents is frequent. Consequently, the mechanisms leading tothis resistance must be understood and addressed. In this paper, we demonstrate that inhibition of deubiquitinylaseUSP7 significantly reduces cell proliferation in vitro and in vivo, blocks DNA replication progression and increases celldeath in AML. Transcriptomic dataset analyses reveal that a USP7 gene signature is highly enriched in cells from AMLpatients at relapse, as well as in residual blasts from patient-derived xenograft (PDX) models treated with clinically relevantdoses of cytarabine, which indicates a relationship between USP7 expression and resistance to therapy. Accordingly, singlecellanalysis of AML patient samples at relapse versus at diagnosis showed that a gene signature of the pre-existingsubpopulation responsible for relapse is enriched in transcriptomes of patients with a high USP7 level. Furthermore, wefound that USP7 interacts and modulates CHK1 protein levels and functions in AML. Finally, we demonstrated that USP7inhibition acts in synergy with cytarabine to kill AML cell lines and primary cells of patients with high USP7 levels.Altogether, these data demonstrate that USP7 is both a marker of resistance to chemotherapy and a potential therapeutictarget in overcoming resistance to treatment.
Published: 2020

18. The INSPIRE research initiative: a program for GeroScience and healthy aging research going from animal models to humans and the healthcare system

Author: Louis Casteilla, Sandrine Andrieu, Pierre Payoux, Isabelle Ader, Cédric Dray, Bruno Vellas, Luc Pénicaud, Roland S. Liblau, Nathalie Vergnolle, P. de Souto Barreto, Yves Rolland, Sophie Guyonnet, Nicolas Fazilleau, Pierre Gourdy, Noélie Davezac, Angelo Parini, Philippe Valet, Claire Rampon, Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Region Auvergne-Rhone-Alpes, Region Bourgogne-Franche-Comte, Region Hauts-de-France, Region Nouvelle-Aquitaine (Reference number: 1901175), European Regional Development Fund (ERDF) (Project number: MP0022856), Inspire Chairs of Excellence - Alzheimer Prevention in Occitania and Catalonia (APOC), EDENIS, KORIAN, Pfizer, Pierre-Fabre, SEGUIN, Nathalie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI)
Subjects: 0301 basic medicine, Gerontology, Gerosciences, medicine.medical_specialty, Research program, Biomedical Research, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Delivery of Health Care, MESH: Geriatrics, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Medicine, MESH: Animals, intrinsic capacity, 030212 general & internal medicine, Healthy aging, Aged, MESH: Aged, Geriatrics, MESH: Humans, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Geroscience, business.industry, MESH: Biomedical Research, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Public health, MESH: Healthy Aging, General Medicine, Risk factor (computing), 3. Good health, Integrated care, 030104 developmental biology, MESH: Models, Animal, biological aging, Models, Animal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Translational science, business, Delivery of Health Care
Abstract: International audience; Aging is the most important risk factor for the onset of several chronic diseases and functional decline. Understanding the interplays between biological aging and the biology of diseases and functional loss as well as integrating a function-centered approach to the care pathway of older adults are crucial steps towards the elaboration of preventive strategies (both pharmacological and non-pharmacological) against the onset and severity of burdensome chronic conditions during aging. In order to tackle these two crucial challenges, ie, how both the manipulation of biological aging and the implementation of a function-centered care pathway (the Integrated Care for Older People (ICOPE) model of the World Health Organization) may contribute to the trajectories of healthy aging, a new initiative on Gerosciences was built: the INSPIRE research program. The present article describes the scientific background on which the foundations of the INSPIRE program have been constructed and provides the general lines of this initiative that involves researchers from basic and translational science, clinical gerontology, geriatrics and primary care, and public health.
Published: 2020

19. Microbiota medicine: towards clinical revolution

Author: Prisca Gebrayel, Carole Nicco, Souhaila Al Khodor, Jaroslaw Bilinski, Elisabetta Caselli, Elena M. Comelli, Markus Egert, Cristina Giaroni, Tomasz M. Karpinski, Igor Loniewski, Agata Mulak, Julie Reygner, Paulina Samczuk, Matteo Serino, Mariusz Sikora, Annalisa Terranegra, Marcin Ufnal, Romain Villeger, Chantal Pichon, Peter Konturek, Marvin Edeas, International Society of Microbiota [Tokyo] (ISM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Lab Excellence GR Ex, Paris, Sidra Medical and Research Center [Doha, Qatar], Medical University of Warsaw - Poland, Università degli Studi di Ferrara = University of Ferrara (UniFE), University of Toronto, Hochschule Furtwangen University [Furtwangen] (HFU), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Pomeranian Medical University [Szczecin] (PUM), Wrocław Medical University, Université Paris Descartes - Paris 5 (UPD5), Medical University of Białystok (MUB), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), National Institute of Geriatrics, Rheumatology & Rehabilitation, Université Clermont Auvergne (UCA), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Jena University Hospital [Jena], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and SEGUIN, Nathalie
Subjects: Fecal microbiota transplant, digestive system, General Biochemistry, Genetics and Molecular Biology, NO, Dysbiosis, Built environment microbiome, Metabolites, miRNAs, Fecal microbiota transplant, Prebiotics, Probiotics, Oral microbiota, Metabolic syndrome, Metabolites, Humans, Built environment microbiome, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, LS6_7, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Microbiota, Probiotics, Dysbiosis, Metabolic syndrome, Oral microbiota, Prebiotics, miRNAs, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Gastrointestinal Microbiome, Gastrointestinal Tract, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.
Published: 2022

20. Co-variation between glucocorticoids, behaviour and immunity supports the pace-of-life syndrome hypothesis: an experimental approach

Author: Rupert Palme, Chloé Monestier, Marie-Line Maublanc, Marine Wasniewski, Benoit Rannou, Guillaume Le Loc’h, Typhaine Lavabre, Emmanuelle Gilot-Fromont, Hélène Verheyden, Luca Börger, Benjamin Rey, Jeffrey Carbillet, Nicolas Cebe, Jean-Luc Rames, Unité de recherche Comportement et Ecologie de la Faune Sauvage (CEFS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), University of Veterinary Medicine [Vienna] (Vetmeduni), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Bankiva, Swansea University, Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inovie Vet, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de la rage et de la faune sauvage de Nancy (LRFSN), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SEGUIN, Nathalie, Marchal-Mauer, Sophie, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), and Laboratoire de Lyon [ANSES]
Subjects: 0106 biological sciences, Hydrocortisone, [SDV.IMM] Life Sciences [q-bio]/Immunology, animal diseases, Adaptive immunity, Physiology, Inflammation, Animals, Wild, Biology, Stress, 010603 evolutionary biology, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Cortisol, 03 medical and health sciences, Immune system, Capreolus, Immunity, biology.animal, medicine, Animals, Glucocorticoids, General Environmental Science, 030304 developmental biology, Innate immunity, 0303 health sciences, Innate immune system, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Immunology and Microbiology, Ecology, Deer, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Medicine, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Acquired immune system, Coping style, 3. Good health, Vaccination, Roe deer, bacteria, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, General Agricultural and Biological Sciences
Abstract: The biomedical literature has consistently highlighted that long-term elevation of glucocorticoids might impair immune functions, while short-term elevation might enhance them. In contrast, in wild and free-ranging animals, patterns are less clear. In the present study, we explored the stress-immunity relationship in controlled conditions, taking into account the potential effects of behavioural profiles. Thirteen captive roe deer (Capreolus capreolus) were monitored over an eight-week period encompassing two capture events. We assessed how changes in baseline faecal cortisol metabolite (FCM) concentrations following a standardised capture protocol and vaccination affected changes in thirteen immune parameters of the innate and adaptive immunity, and whether behavioural profiles were linked to changes in baseline FCM levels and immune parameters. We found that individuals showing an increase in baseline FCM levels over time also exhibited an increase in immunity, for both the innate and adaptive immunity and were characterised by more reactive behavioural profiles (as indicated by low activity levels, docility to manipulation and neophilia). Consequently, our results suggest that immunity of large mammals may be influenced by their stress level, but also by their behavioural profiles, as it is predicted by the pace-of-life syndrome hypothesis. Our analysis therefore highlights the need to consider co-variations between behavioural profiles, immunity and stress hormones in order to gain a better understanding of the unexplained among-individual variability in the glucocorticoids-immunity relationships observed in wildlife, as they may be underpinned by different life-history strategies.
Published: 2022

21. Postoperative ileus: A pharmacological perspective

Author: Etienne Buscail, Céline Deraison, SEGUIN, Nathalie, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ingénierie Radioprotection Sûreté Démantèlement (IRSD), and Centre National de la Recherche Scientifique (CNRS)
Subjects: Pharmacology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV.CAN]Life Sciences [q-bio]/Cancer, gastro intestinal, postoperative ileus, Analgesics, Opioid, surgery, Ileus, Postoperative Complications, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Risk Factors, inflammation, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Postoperative ileus (POI) is a frequent complication after abdominal surgery. The consequences of postoperative ileus can be potentially serious such as bronchial inhalation or acute functional renal failure. Numerous advances in peri-operative management, particularly early rehabilitation, have made it possible to decrease postoperative ileus. Despite this, the rate of prolonged postoperative ileus remains high and can be as high as 25% of patients in colorectal surgery. From a pathophysiological point of view, postoperative ileus has two phases, an early neurological phase and a later inflammatory phase, to which we could add a 'pharmacological' phase during which analgesic drugs, particularly opiates, play a central role. The aim of this review article is to describe the phases of the pathophysiology of postoperative ileus, to analyse the pharmacological treatments currently available through published clinical trials and finally to discuss the different research areas for potential pharmacological targets.
Published: 2022

22. Screening for β-lactam resistance by penicillin G in the Streptococcus anginosus group challenged by rare strains with altered PBPs

Author: Camille V Chagneau, Orancie Alcouffe, Marion Grare, Eric Oswald, Clémence Massip, SEGUIN, Nathalie, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Pharmacology, Microbiology (medical), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Penicillin Resistance, Amoxicillin, Reproducibility of Results, Microbial Sensitivity Tests, Penicillins, biochemical phenomena, metabolism, and nutrition, beta-Lactams, beta-Lactam Resistance, Anti-Bacterial Agents, Cephalosporins, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Streptococcus anginosus, polycyclic compounds, Penicillin-Binding Proteins, Pharmacology (medical), [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Streptococcus anginosus group (SAG) strains are common pathogens causing abscesses and bacteraemia. They are generally susceptible to β-lactams, which constitute first-line treatment. EUCAST recommends testing penicillin G susceptibility to screen for β-lactam resistance. Isolates categorized as susceptible (negative screening) can be reported as susceptible to aminopenicillins and third-generation cephalosporins. Objectives To assess the reliability of penicillin G resistance screening in predicting β-lactam resistance in SAG blood culture isolates, and to investigate isolates for which this test would be unreliable. Methods We determined the susceptibility to penicillin G, amoxicillin and ceftriaxone of 90 SAG blood culture isolates, all with negative penicillin G resistance screening. β-Lactam-resistant strains were sequenced and compared with susceptible reference SAG strains. Results We detected two isolates displaying β-lactam resistance, especially to third-generation cephalosporins, despite negative screening for penicillin G resistance. For these isolates, amino acid substitutions were identified next to the essential PBP motifs SxxK, SxN and/or KS/TGS/T. Changes in these motifs have been previously linked to β-lactam resistance in Streptococcus pneumoniae. Conclusions Our study suggests that aminopenicillin and third-generation cephalosporin susceptibility should be determined for SAG strains in the event of severe infection as screening for penicillin G resistance might not be sufficient to detect resistance mechanisms that predominantly affect cephalosporins. The PBP sequencing of resistant SAG strains allowed us to detect amino acid changes potentially linked to β-lactam resistance.
Published: 2022

23. Global population structure of the Serratia marcescens complex and identification of hospital-adapted lineages in the complex

Author: Tomoyuki Ono, Itsuki Taniguchi, Keiji Nakamura, Debora Satie Nagano, Ruriko Nishida, Yasuhiro Gotoh, Yoshitoshi Ogura, Mitsuhiko P. Sato, Atsushi Iguchi, Kazunori Murase, Dai Yoshimura, Takehiko Itoh, Ayaka Shima, Damien Dubois, Eric Oswald, Akira Shiose, Naomasa Gotoh, Tetsuya Hayashi, SEGUIN, Nathalie, Kyushu University, Faculty of Medicine, Kyushu University, Kurume University School of Medicine, Kurume University, University of Miyazaki, Kyoto University, Tokyo Institute of Technology [Tokyo] (TITECH), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Anicon Insurance, Kyoto Prefectural University of Medicine [Kyoto, Japon], KAKENHI from the Japan Society for the Promotion of Science (18K16175), and Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
Subjects: Serratia marcescens complex, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], population structure, General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, genomics, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], hospital-adapted lineage, antimicrobial resistance, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Serratia marcescens is an important nosocomial pathogen causing various opportunistic infections, such as urinary tract infections, bacteremia and sometimes even hospital outbreaks. The recent emergence and spread of multidrug-resistant (MDR) strains further pose serious threats to global public health. This bacterium is also ubiquitously found in natural environments, but the genomic differences between clinical and environmental isolates are not clear, including those between S. marcescens and its close relatives. In this study, we performed a large-scale genome analysis of S. marcescens and closely related species (referred to as the ‘ S. marcescens complex’), including more than 200 clinical and environmental strains newly sequenced here. Our analysis revealed their phylogenetic relationships and complex global population structure, comprising 14 clades, which were defined based on whole-genome average nucleotide identity. Clades 10, 11, 12 and 13 corresponded to S. nematodiphila , S. marcescens sensu stricto, S. ureilytica and S. surfactantfaciens, respectively. Several clades exhibited distinct genome sizes and GC contents and a negative correlation of these genomic parameters was observed in each clade, which was associated with the acquisition of mobile genetic elements (MGEs), but different types of MGEs, plasmids or prophages (and other integrative elements), were found to contribute to the generation of these genomic variations. Importantly, clades 1 and 2 mostly comprised clinical or hospital environment isolates and accumulated a wide range of antimicrobial resistance genes, including various extended-spectrum β-lactamase and carbapenemase genes, and fluoroquinolone target site mutations, leading to a high proportion of MDR strains. This finding suggests that clades 1 and 2 represent hospital-adapted lineages in the S. marcescens complex although their potential virulence is currently unknown. These data provide an important genomic basis for reconsidering the classification of this group of bacteria and reveal novel insights into their evolution, biology and differential importance in clinical settings.
Published: 2022

24. An ESPGHAN Position Paper on the Use of Low-FODMAP Diet in Pediatric Gastroenterology

Author: Thomassen, R A, Luque, V, Assa, A, Borrelli, O, Broekaert, I, Dolinsek, J, Martin-de-Carpi, J, Mas, E, Miele, E, Norsa, L, Ribes-Koninckx, C, Saccomani, M Deganello, Thomson, M, Tzivinikos, C, Verduci, E, Bronsky, J, Haiden, N, Köglmeier, J, de Koning, B, Benninga, M A, Pediatrics, Paediatric Gastroenterology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), Oslo University Hospital [Oslo], Universitat Rovira i Virgili, The Hebrew University of Jerusalem (HUJ), Great Ormond Street Hospital for Children [London] (GOSH), University Hospital of Cologne [Cologne], University of Maribor, University of Barcelona, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Naples Federico II = Università degli studi di Napoli Federico II, ASST Papa Giovanni XXIII [Bergamo, Italy], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Inst Invest Sanitaria La FE, Sheffield Children's NHS Foundation Trust, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Università degli Studi di Milano = University of Milan (UNIMI), University Hospital Motol [Prague], Medizinische Universität Wien = Medical University of Vienna, Erasmus University Rotterdam, University of Amsterdam [Amsterdam] (UvA), SEGUIN, Nathalie, Thomassen, R A, Luque, V, Assa, A, Borrelli, O, Broekaert, I, Dolinsek, J, Martin-de-Carpi, J, Mas, E, Miele, E, Norsa, L, Ribes-Koninckx, C, Saccomani, M Deganello, Thomson, M, Tzivinikos, C, Verduci, E, Bronsky, J, Haiden, N, Köglmeier, J, de Koning, B, and Benninga, M A
Subjects: IRRITABLE-BOWEL-SYNDROME, Oligosaccharides, CHILDREN, Disaccharides, POLYOLS DIET, CLINICAL-TRIAL, Irritable Bowel Syndrome, Diet, Carbohydrate-Restricted, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, QUALITY-OF-LIFE, MANAGEMENT, Humans, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, REDUCES SYMPTOMS, Child, Settore MED/38 - Pediatria Generale e Specialistica, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Monosaccharides, Gastroenterology, RANDOMIZED CONTROLLED-TRIAL, Diet, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Fermentation, Pediatrics, Perinatology and Child Health, LOW FERMENTABLE OLIGOSACCHARIDES, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CELIAC GLUTEN SENSITIVITY, Systematic Reviews as Topic
Abstract: OBJECTIVES: Excluding oligo-, di-, monosaccharides and polyols (FODMAPs) from the diet is increasingly being used to treat children with gastrointestinal complaints. The aim of this position paper is to review the available evidence on the safety and efficacy of its use in children and provide expert guidance regarding practical aspects in case its use is considered. METHODS: Members of the Gastroenterology Committee, the Nutrition Committee and the Allied Health Professionals Committee of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Clinical questions regarding initiation, introduction, duration, weaning, monitoring, professional guidance, safety and risks of the diet are addressed. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. RESULTS: The systematic literature search revealed that the low-FODMAP diet has not been comprehensively studied in children. Indications and contraindications of the use of the diet in different pediatric gastroenterological conditions are discussed and practical recommendations are formulated. CONCLUSIONS: There is scarce evidence to support the use of a low-FODMAP diet in children with Irritable Bowel Syndrome and no evidence to recommend its use in other gastrointestinal diseases and complaints in children. Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects. The present manuscript provides practical safety tips to be applied when the low-FODMAP diet is considered in children.
Published: 2022

25. Identification of bacterial lipopeptides as key players in IBS

Author: Camille Petitfils, Sarah Maurel, Gaelle Payros, Amandine Hueber, Bahija Agaiz, Géraldine Gazzo, Rémi Marrocco, Frédéric Auvray, Geoffrey Langevin, Jean-Paul Motta, Pauline Floch, Marie Tremblay-Franco, Jean-Marie Galano, Alexandre Guy, Thierry Durand, Simon Lachambre, Anaëlle Durbec, Hind Hussein, Lisse Decraecker, Justine Bertrand-Michel, Abdelhadi Saoudi, Eric Oswald, Pierrick Poisbeau, Gilles Dietrich, Chloe Melchior, Guy Boeckxstaens, Matteo Serino, Pauline Le Faouder, Nicolas Cenac, SEGUIN, Nathalie, APPEL À PROJETS GÉNÉRIQUE 2018 - Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable - - LiBacPain2018 - ANR-18-CE14-0039 - AAPG2018 - VALID, Signalisation des lipides du microbiote sur l'hôte - - MILI2020 - ANR-20-CE14-0011 - AAPG2020 - VALID, Ecole Universitaire de Recherche Interdisciplinaire sur la Douleur - - EURIDOL2017 - ANR-17-EURE-0022 - EURE - VALID, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul Lipidomics, MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Gothenburg (GU), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Federation pour la Recherche sur le Cerveau (FRC) FRC20200411001, Centre National de la Recherche Scientifique. PP and GG received support from CNRS and University of Strasbourg. GG, CP and SM received a scholarship from Ministere de l'Enseignement Superieur, de la YRecherche et de l'Innovation., ANR-18-CE14-0039,LiBacPain,Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable(2018), ANR-20-CE14-0011,MILI,Signalisation des lipides du microbiote sur l'hôte(2020), ANR-17-EURE-0022,EURIDOL,Ecole Universitaire de Recherche Interdisciplinaire sur la Douleur(2017), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), and ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011)
Subjects: VISCERAL HYPERSENSITIVITY, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, IRRITABLE-BOWEL-SYNDROME, IRRITABLE BOWEL SYNDROME, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ENTERIC BACTERIAL MICROFLORA, PRENATAL STRESS, INTESTINAL MICROBIOTA, LACTIC ACID BACTERIA, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC] Life Sciences [q-bio]/Cellular Biology, CLOSTRIDIUM-CLOSTRIDIOFORME, RISK, Science & Technology, Gastroenterology & Hepatology, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, SEVERITY, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Life Sciences & Biomedicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, LIPIDS
Abstract: ObjectivesClinical studies revealed that early-life adverse events contribute to the development of IBS in adulthood. The aim of our study was to investigate the relationship between prenatal stress (PS), gut microbiota and visceral hypersensitivity with a focus on bacterial lipopeptides containing γ-aminobutyric acid (GABA).DesignWe developed a model of PS in mice and evaluated, in adult offspring, visceral hypersensitivity to colorectal distension (CRD), colon inflammation, barrier function and gut microbiota taxonomy. We quantified the production of lipopeptides containing GABA by mass spectrometry in a specific strain of bacteria decreased in PS, in PS mouse colons, and in faeces of patients with IBS and healthy volunteers (HVs). Finally, we assessed their effect on PS-induced visceral hypersensitivity.ResultsPrenatally stressed mice of both sexes presented visceral hypersensitivity, no overt colon inflammation or barrier dysfunction but a gut microbiota dysbiosis. The dysbiosis was distinguished by a decreased abundance ofLigilactobacillus murinus, in both sexes, inversely correlated with visceral hypersensitivity to CRD in mice. An isolate from this bacterial species produced several lipopeptides containing GABA including C14AsnGABA. Interestingly, intracolonic treatment with C14AsnGABA decreased the visceral sensitivity of PS mice to CRD. The concentration of C16LeuGABA, a lipopeptide which inhibited sensory neurons activation, was decreased in faeces of patients with IBS compared with HVs.ConclusionPS impacts the gut microbiota composition and metabolic function in adulthood. The reduced capacity of the gut microbiota to produce GABA lipopeptides could be one of the mechanisms linking PS and visceral hypersensitivity in adulthood.
Published: 2022

26. High Fecal Prevalence of mcr-Positive Escherichia coli in Veal Calves at Slaughter in France

Author: Maryse Michèle Um, Véronique Dupouy, Nathalie Arpaillange, Clémence Bièche-Terrier, Frédéric Auvray, Eric Oswald, Hubert Brugère, Delphine Bibbal, SEGUIN, Nathalie, Ingénierie Radioprotection Sûreté Démantèlement (IRSD), Centre National de la Recherche Scientifique (CNRS), Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de l'élevage (IDELE), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and French Ministry of Agriculture and Food
Subjects: Microbiology (medical), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Escherichia coli, mcr genes, colistin, extended spectrum β-lactamase, critically important antibiotics, healthy veal calves, Biochemistry, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, extended spectrum beta-lactamase, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Infectious Diseases, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The aim of this study was to determine the percentage of healthy veal calves carrying mcr-positive E. coli strains at the time of slaughter in France. Fecal samples were selectively screened for mcr-positive E. coli isolates using media supplemented with colistin. Screening for mcr genes was also carried out in E. coli isolates resistant to critically important antimicrobials used in human medicine recovered from the same fecal samples. Overall, 28 (16.5%) out of the 170 veal calves tested carried mcr-positive E. coli. As some calves carried several non-redundant mcr-positive strains, 41 mcr-positive E. coli were recovered. Thirty-one and seven strains were positive for mcr-1 and mcr-3 genes, respectively, while no strain was positive for the mcr-2 gene. Co-carriage of mcr-1 and mcr-3 was identified in three strains. All mcr-positive E. coli isolates, except one, were multidrug-resistant, with 56.1% being ciprofloxacin-resistant and 31.7% harboring blaCTX-M genes. All mcr-3-positive E. coli carried blaCTX-M genes, mainly blaCTX-M-55. This study highlights the high prevalence of mcr-positive E. coli strains in feces of veal calves at the time of slaughter. It also points out the multidrug (including ciprofloxacin) resistance of such strains and the co-occurrence of mcr-3 genes with blaCTX-M-55 genes.
Published: 2022

27. Tackling the Threat of Cancer Due to Pathobionts Producing Colibactin: Is Mesalamine the Magic Bullet?

Author: Min Tang-Fichaux, Priscilla Branchu, Jean-Philippe Nougayrède, Eric Oswald, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and SEGUIN, Nathalie
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Health, Toxicology and Mutagenesis, Anti-Inflammatory Agents, Non-Steroidal, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, Review, Toxicology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, mesalamine, [SDV.CAN] Life Sciences [q-bio]/Cancer, inflammatory bowel disease, Neoplasms, Polyketides, Escherichia coli, polycyclic compounds, Humans, Medicine, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, colibactin, polyphosphate kinase, Peptides, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Colibactin is a genotoxin produced primarily by Escherichia coli harboring the genomic pks island (pks+ E. coli). Pks+ E. coli cause host cell DNA damage, leading to chromosomal instability and gene mutations. The signature of colibactin-induced mutations has been described and found in human colorectal cancer (CRC) genomes. An inflamed intestinal environment drives the expansion of pks+ E. coli and promotes tumorigenesis. Mesalamine (i.e., 5-aminosalycilic acid), an effective anti-inflammatory drug, is an inhibitor of the bacterial polyphosphate kinase (PPK). This drug not only inhibits the production of intestinal inflammatory mediators and the proliferation of CRC cells, but also limits the abundance of E. coli in the gut microbiota and diminishes the production of colibactin. Here, we describe the link between intestinal inflammation and colorectal cancer induced by pks+ E. coli. We discuss the potential mechanisms of the pleiotropic role of mesalamine in treating both inflammatory bowel diseases and reducing the risk of CRC due to pks+ E. coli.
Published: 2021

28. Reply to Dubbert and von Bünau, 'A Probiotic Friend'

Author: Eric Oswald, Jean-Philippe Nougayrede, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and SEGUIN, Nathalie
Subjects: Author Reply, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Escherichia coli Proteins, Probiotics, Friends, Microbiology, QR1-502, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Humans, Molecular Biology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2021

29. Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic, Prognostic and Therapeutic Tools?

Author: Frédérick Barreau, Emmanuel Mas, Alexis Cassard, Vickie Lacroix, CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CHU Toulouse [Toulouse], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DGOS (Reference Center of Rare Digestive Diseases of Toulouse University Hospital), the patient association François Aupetit, Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and SEGUIN, Nathalie
Subjects: Crohn’s disease, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Review, Disease, Gut flora, Bioinformatics, Inflammatory bowel disease, 0302 clinical medicine, A, E, Precision Medicine, Biology (General), Phylogeny, Spectroscopy, 0303 health sciences, Crohn's disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Microbiota, General Medicine, Ulcerative colitis, 3. Good health, Computer Science Applications, Chemistry, Mas, Disease Progression, 030211 gastroenterology & hepatology, F. Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic, QH301-705.5, Omics, digestive system, eulcerative colitis, Catalysis, Inorganic Chemistry, 03 medical and health sciences, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Barreau, 030304 developmental biology, Bacteria, business.industry, V, Organic Chemistry, Cassard, Lacroix, Inflammatory Bowel Diseases, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, digestive system diseases, Prognostic inflammatory bowel disease, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Gastrointestinal Microbiome, Crohn's diseas, Metagenomics, Personalized medicine, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Dysbiosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Inflammatory bowel diseases (IBDs), which include Crohn’s disease and ulcerative colitis, are multifactorial diseases that involve in particular a modification of the gut microbiota, known as dysbiosis. The initial sets of metataxonomic and metagenomic data first made it possible to approximate the microbiota profile in IBD. In addition, today the new ‘omics’ techniques have enabled us to draw up a functional and integrative map of the microbiota. The key concern in IBD is to develop biomarkers that allow us to assess the activity of the disease and predict the complications and progression, while also guiding the therapeutic care so as to develop personalized medicine. In this review, we present all of the latest discoveries on the microbiota provided by “omics” and we outline the benefits of these techniques in developing new diagnostic, prognostic and therapeutic tools.
Published: 2021

30. High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis

Author: Troy D Feener, Jean-Paul Motta, Andre G. Buret, Elena Fekete, Dimitri Desmonts de Lamache, Raylene A. Reimer, Dezirae Leger, Olivia Sosnowski, Thibault Allain, University of Calgary, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and SEGUIN, Nathalie
Subjects: Giardiasis, Male, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Gut flora, Pathogenesis, Mice, fluids and secretions, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Diet, Fat-Restricted, 2. Zero hunger, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Fatty Acids, Giardia, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Pathophysiology, 3. Good health, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Cytokines, medicine.medical_specialty, Firmicutes, Science, Crypt, Diet, High-Fat, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Trophozoites, 030304 developmental biology, Inflammation, Tight Junction Proteins, 030306 microbiology, biology.organism_classification, medicine.disease, Mucus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, digestive system diseases, Gastrointestinal Microbiome, Mice, Inbred C57BL, Endocrinology, Dysbiosis, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Exogenous factors that may influence the pathophysiology of Giardia infection remain incompletely understood. We have investigated the role of dietary fat in the pathogenesis of Giardia infection. Male 3 to 4-week-old C57BL/6 mice were fed either a low fat (LF) or a high fat (HF) diet for 12 days and challenged with G. duodenalis. In infected animals, the trophozoite burden was higher in HF + Giardia mice compared to the LF + Giardia group at day 7 post infection. Fatty acids exerted direct pro-growth effects on Giardia trophozoites. Analysis of disease parameters showed that HF + Giardia mice exhibited more mucosal infiltration by inflammatory cells, decreased villus/crypt ratios, goblet cell hyperplasia, mucus disruption, increased gut motility, and elevated fecal water content compared with LF + Giardia. HF diet-dependent exacerbation of Giardia-induced goblet cell hyperplasia was associated with elevated Atoh1 and Muc2 gene expression. Gut microbiota analysis revealed that the HF diet alone induces a taxonomic shift. HF + Giardia mice exhibited microbiota dysbiosis characterized by an increase of Firmicutes and a decrease of Bacteroidetes and significant changes in α- and β-diversity metrics. Taken together, the findings suggest that a HF diet exacerbates the outcome of Giardia infection. The data demonstrate that elevated dietary fat represents an important exogenous factor promoting the pathophysiology of giardiasis.
Published: 2021

31. A Toxic Friend: Genotoxic and Mutagenic Activity of the Probiotic Strain Escherichia coli Nissle 1917

Author: Eric Oswald, Marcy Belloy, Nadège Bossuet-Greif, Jean-Philippe Nougayrède, Jean-Paul Motta, Camille V. Chagneau, Jean-Jacques Gratadoux, Frédéric Taieb, Philippe Langella, Muriel Thomas, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National Du Cancer (INCA PLBIO13-123), European Project: 609398,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,AGREENSKILLSPLUS(2014), SEGUIN, Nathalie, AgreenSkills+ - AGREENSKILLSPLUS - - EC:FP7:PEOPLE2014-05-05 - 2019-05-04 - 609398 - VALID, CHU Toulouse [Toulouse], Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: DNA damage, Mutaflor, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Biology, Gene mutation, medicine.disease_cause, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Microbiology, law.invention, 03 medical and health sciences, Probiotic, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, law, medicine, Escherichia coli, genotoxin, Gene, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 030306 microbiology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pathogenicity island, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, QR1-502, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain, nervous system, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, colibactin, probiotic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: The probioticEscherichia colistrain Nissle 1917 (DSM 6601, Mutaflor), generally considered as beneficial and safe, has been used for a century to treat various intestinal diseases. However, Nissle 1917 hosts in its genome thepkspathogenicity island that codes for the biosynthesis of the genotoxin colibactin. Colibactin is a potent DNA alkylator, suspected to play a role in colorectal cancer development. We show in this study that Nissle 1917 is functionally capable of producing colibactin and inducing interstrand crosslinks in the genomic DNA of epithelial cells exposed to the probiotic. This toxicity was even exacerbated with lower doses of the probiotic, when the exposed cells started to divide again but exhibited aberrant anaphases and increased gene mutation frequency. DNA damage was confirmedin vivoin mouse models of intestinal colonization, demonstrating that Nissle 1917 produces the genotoxin in the gut lumen. Although it is possible that daily treatment of adult humans with their microbiota does not produce the same effects, administration of Nissle 1917 as a probiotic or as a chassis to deliver therapeutics might exert long term adverse effects and thus should be considered in a risk versus benefit evaluation.ImportanceNissle 1917 is sold as a probiotic and considered safe even though it is known since 2006 that it encodes the genes for colibactin synthesis. Colibactin is a potent genotoxin that is now linked to causative mutations found in human colorectal cancer. Many papers concerning the use of this strain in clinical applications ignore or elude this fact, or misleadingly suggest that Nissle 1917 does not induce DNA damage. Here, we demonstrate that Nissle 1917 produces colibactinin vitroandin vivoand induces mutagenic DNA damage. This is a serious safety concern that must not be ignored, for the interests of patients, the general public, health care professionals and ethical probiotic manufacturers.
Published: 2021

32. Titanium dioxide particles from the diet: involvement in the genesis of inflammatory bowel diseases and colorectal cancer

Author: Frédérick Barreau, Sandrine Ménard, Céline Tisseyre, Audrey Ferrand, Marie Carrière, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), French Atomic Energy and Alternative Energies Commission (CEA) : [grant: IMAGINATOX], French Environment and Energy Management Agency (ADEME), French Plan Cancer [grant: SiFoodCan grant], Association Francois Au Petit (AFA), ANR-16-CE34-0011,PAIPITO,Particules Alimentaires: Inflammation, Pathologies Intestinales et Tolérance Orale(2016), ANR-20-CE34-0010,INPAGE,Approche intégrative pour déterminer le devenir des nanoparticules dans un écosystème agricole(2020), ANR-11-LABX-0064,SERENADE,Vers une conception de nanomatériaux innovants, durables et sûrs(2011), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), SEGUIN, Nathalie, Particules Alimentaires: Inflammation, Pathologies Intestinales et Tolérance Orale - - PAIPITO2016 - ANR-16-CE34-0011 - AAPG2016 - VALID, Approche intégrative pour déterminer le devenir des nanoparticules dans un écosystème agricole - - INPAGE2020 - ANR-20-CE34-0010 - AAPG2020 - VALID, Vers une conception de nanomatériaux innovants, durables et sûrs - - SERENADE2011 - ANR-11-LABX-0064 - LABX - VALID, INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE - - Amidex2011 - ANR-11-IDEX-0001 - IDEX - VALID, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Colorectal cancer, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Health, Toxicology and Mutagenesis, Review, 02 engineering and technology, Toxicology, Inflammatory bowel disease, Gastrointestinal tract, RA1190-1270, Ingestion, TiO2, Intestinal Mucosa, Barrier function, Cancer, Titanium, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Medicine, HD7260-7780.8, 021001 nanoscience & nanotechnology, 3. Good health, Intestine, medicine.symptom, Colorectal Neoplasms, 0210 nano-technology, TiO 2, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, 030304 developmental biology, Food additive, Toxicity, business.industry, Inflammatory Bowel Diseases, medicine.disease, Diet, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Toxicology. Poisons, Immunology, Industrial hygiene. Industrial welfare, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The gastrointestinal tract is a complex interface between the external environment and the immune system. Its ability to control uptake across the mucosa and to protect the body from damage of harmful substances from the lumen is defined as the intestinal barrier function (IBF). The IBF involves four elements: the intestinal microbiota, the mucus layer, the epithelium and the immune system. Its dysfunction is linked with human diseases including inflammatory, metabolic, infectious, autoimmune and neurologic disorders. Most of these diseases are complex and involve genetic, psychological and environmental factors. Over the past 10 years, many genetic polymorphisms predisposing to inflammatory bowel disease (IBD) have been identified. Yet, it is now clear that they are insufficient to explain the onset of these chronic diseases. Although it has been evidenced that some environmental factors such as cigarette smoking or carbohydrate intake are associated with IBD, other environmental factors also present potential health risks such as ingestion of food additives introduced in the human diet, including those composed of mineral particles, by altering the four elements of the intestinal barrier function. The aim of this review is to provide a critical opinion on the potential of TiO2 particles, especially when used as a food additive, to alter the four elements of the intestinal barrier function, and consequently to evaluate if this additive would likely play a role in the development and/or exacerbation of IBD. Supplementary Information The online version contains supplementary material available at 10.1186/s12989-021-00421-2.
Published: 2021

33. An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology

Author: Rut Ann Thomassen, Jernej Dolinsek, Carmen Ribes-Koninckx, Erasmo Miele, Christos Tzivinikos, Corina Pienar, Javier Martín-de-Carpi, Emmanuel Mas, Marc A. Benninga, Osvaldo Borrelli, Ilse Broekaert, Mike Thomson, University Hospital of Cologne [Cologne], Great Ormond Street Hospital for Children [London] (GOSH), University medical centre Maribor (UKC Maribor), Hospital Sant Joan de Déu [Barcelona], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Oslo University Hospital [Oslo], Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, VU University Medical Center [Amsterdam], SEGUIN, Nathalie, Broekaert, Ilse Julia, Borrelli, Osvaldo, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Ribes-Koninckx, Carmen, Thomassen, Rut, Thomson, Mike, Tzivinikos, Christo, Benninga, Marc, and Hospital Universitari i Politècnic La Fe
Subjects: medicine.medical_specialty, Malabsorption, Consensus, Carbohydrate malabsorption, 030309 nutrition & dietetics, MEDLINE, carbohydrate malabsorption, small intestinal bacterial overgrowth, Helicobacter pylori infection, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, children, Internal medicine, Small intestinal bacterial overgrowth, medicine, breath testing, Humans, Intensive care medicine, Exocrine pancreatic insufficiency, Child, Children, 0303 health sciences, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Fat malabsorption, Breath testing, Systematic review, Breath Tests, Pediatrics, Perinatology and Child Health, Position paper, 030211 gastroenterology & hepatology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Systematic Reviews as Topic
Abstract: International audience; Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.
Published: 2021

34. Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice

Author: Mas-Orea, Xavier, Sebert, Morgane, Benamar, Mehdi, Petitfils, Camille, Blanpied, Catherine, Saoudi, Abdelhadi, Deraison, Céline, Barreau, Frederick, Cenac, Nicolas, Dietrich, Gilles, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), association Francois Aupetit, AFA2019/Association Francois Aupetit, and SEGUIN, Nathalie
Subjects: CD4-Positive T-Lymphocytes, MESH: Colitis / chemically induced, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], colitis, Narcotic Antagonists, MESH: Animals, Deraison, MESH: Anti-Inflammatory Agents, Non-Steroidal / pharmacology, Anti-Inflammatory Agents, MESH: Epithelial Cells / drug effects, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Severity of Illness Index, M, Blanpied, Mice, MESH: Inflammation / metabolism, A, Biology (General), Intestinal Mucosa, MESH: Apoptosis / genetics, Mice, Knockout, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Naloxone, scolitis, Anti-Inflammatory Agents, Non-Steroidal, Saoudi, MESH: CD4-Positive T-Lymphocytes / drug effects, apoptosis, MESH: Apoptosis / drug effects, Cenac, Interleukin-10, Chemistry, Mas-Orea, Petitfils, Sebert, Cytokines, G. Peripheral Opioid Receptor Blockade Enhances opioids, QH301-705.5, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, Permeability, MESH: Colitis / genetics, C, MESH: Anti-Inflammatory Agents / pharmacology, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Dietrich, X, QD1-999, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Benamar, Barreau, Inflammation, intestinal permeability, piroxicam, MESH: Cytokines / metabolism, MESH: Inflammation / genetics, opioids, Epithelial Cells, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, N, MESH: Cytokines / genetics, Mice, Inbred C57BL, Quaternary Ammonium Compounds, IL-10-deficient mice, F, Receptors, Opioid, opioid, MESH: Colitis / metabolism, MESH: Colitis / pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Mucosal CD4+ T lymphocytes display a potent opioid-mediated analgesic activity in interleukin (IL)-10 knockout mouse model of inflammatory bowel diseases (IBD). Considering that endogenous opioids may also exhibit anti-inflammatory activities in the periphery, we examined the consequences of a peripheral opioid receptor blockade by naloxone-methiodide, a general opioid receptor antagonist unable to cross the blood–brain barrier, on the development of piroxicam-accelerated colitis in IL-10-deficient (IL-10-/-) mice. Here, we show that IL-10-deficient mice treated with piroxicam exhibited significant alterations of the intestinal barrier function, including permeability, inflammation-related bioactive lipid mediators, and mucosal CD4+ T lymphocyte subsets. Opioid receptor antagonization in the periphery had virtually no effect on colitis severity but significantly worsened epithelial cell apoptosis and intestinal permeability. Thus, although the endogenous opioid tone is not sufficient to reduce the severity of colitis significantly, it substantially contributes to the protection of the physical integrity of the epithelial barrier.
Published: 2021

35. Diagnosis, Management, and Prevention of Button Battery Ingestion in Childhood: A European Society for Paediatric Gastroenterology Hepatology and Nutrition Position Paper

Author: Matjaž Homan, Nikhil Thapar, Mike Thomson, Christos Tzivinikos, Lissy de Ridder, Amani Mubarak, Emmanuel Mas, Marc A. Benninga, Ilse Broekaert, Corina Pienar, Jernej Dolinsek, Erasmo Miele, University Medical Center [Utrecht], Emma Children’s Hospital, University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Great Ormond Street Hospital for Children [London] (GOSH), Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, Eramus MC-Sophia Children’s Hospital, Partenaires INRAE, Nestle SA, Danone Nutricia, Mubarak, Amani, Benninga, Marc A, Broekaert, Ilse, Dolinsek, Jernej, Homan, Matjaž, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Thapar, Nikhil, Thomson, Mike, Tzivinikos, Christo, de Ridder, Lissy, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, SEGUIN, Nathalie, and Pediatrics
Subjects: medicine.medical_specialty, MEDLINE, [SPI.MAT] Engineering Sciences [physics]/Materials, Asymptomatic, [SPI.MAT]Engineering Sciences [physics]/Materials, Eating, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Electric Power Supplies, Esophagus, 0302 clinical medicine, SDG 3 - Good Health and Well-being, 030225 pediatrics, Internal medicine, medicine, Humans, endoscopy, Child, Intensive care medicine, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, medicine.diagnostic_test, Impaction, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Guideline, Hepatology, Foreign Bodies, foreign body, esophageal perforation, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Endoscopy, caustic ingestion, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, medicine.anatomical_structure, pediatric, Pediatrics, Perinatology and Child Health, Position paper, 030211 gastroenterology & hepatology, medicine.symptom, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the esophagus. Worldwide initiatives have been set up in order to prevent and also timely diagnose and manage BB ingestions. A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) task force for BB ingestions has been founded, which aimed to contribute to reducing the health risks related to this event. It is important to focus on the European setting, next to other worldwide initiatives, to develop and implement effective management strategies. As one of the first initiatives of the ESPGHAN task force, this ESPGHAN position paper has been written. The literature is summarized, and prevention strategies are discussed focusing on some controversial topics. An algorithm for the diagnosis and management of BB ingestions is presented and compared to previous guidelines (NASPGHAN, National Poison Center). In agreement with earlier guidelines, immediate localization of the BB is important and in case of esophageal impaction, the BB should be removed instantly (preferably 12 hours after ingestion or time point of removal >12 hours after ingestion) and esophageal impaction the guideline suggests to perform a CT scan in order to evaluate for vascular injury before removing the battery. In delayed diagnosis, even if the battery has passed the esophagus, endoscopy to screen for esophageal damage and a CT scan to rule out vascular injury should be considered even in asymptomatic children. In asymptomatic patients with early diagnosis (
Published: 2021

36. Insights into evolution and coexistence of the colibactin- and yersiniabactin secondary metabolite determinants in enterobacterial populations

Author: Monika Stoll, Ulrich Dobrindt, Alexander Wallenstein, Eric Oswald, Rudolf von Bünau, Haleluya Wami, Daniel Sauer, Rolf Müller, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Saarland University [Saarbrücken], Ardeypharm, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), German Research Foundation : grant DO789/11-1, German Research Foundation : 281125614/GRK2220, EvoPAD project A3, SEGUIN, Nathalie, and HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
Subjects: Gene Transfer, Horizontal, Operon, Secondary Metabolism, secondary metabolite, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, medicine.disease_cause, Genome, Yersiniabactin, cytopathic effect, high pathogenicity island, 03 medical and health sciences, chemistry.chemical_compound, Citrobacter, polyketide, Enterobacteriaceae, Phenols, Klebsiella, Gene cluster, medicine, Escherichia coli, Humans, Gene, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Genetics, 0303 health sciences, biology, 030306 microbiology, Escherichia coli Proteins, General Medicine, Gene Expression Regulation, Bacterial, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Thiazoles, chemistry, Polyketides, Horizontal gene transfer, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Peptides, Mutagens
Abstract: The bacterial genotoxin colibactin interferes with the eukaryotic cell cycle by causing dsDNA breaks. It has been linked to bacterially induced colorectal cancer in humans. Colibactin is encoded by a 54 kb genomic region in Enterobacteriaceae . The colibactin genes commonly co-occur with the yersiniabactin biosynthetic determinant. Investigating the prevalence and sequence diversity of the colibactin determinant and its linkage to the yersiniabactin operon in prokaryotic genomes, we discovered mainly species-specific lineages of the colibactin determinant and classified three main structural settings of the colibactin–yersiniabactin genomic region in Enterobacteriaceae . The colibactin gene cluster has a similar but not identical evolutionary track to that of the yersiniabactin operon. Both determinants could have been acquired on several occasions and/or exchanged independently between enterobacteria by horizontal gene transfer. Integrative and conjugative elements play(ed) a central role in the evolution and structural diversity of the colibactin–yersiniabactin genomic region. Addition of an activating and regulating module (clbAR) to the biosynthesis and transport module (clbB-S) represents the most recent step in the evolution of the colibactin determinant. In a first attempt to correlate colibactin expression with individual lineages of colibactin determinants and different bacterial genetic backgrounds, we compared colibactin expression of selected enterobacterial isolates in vitro. Colibactin production in the tested Klebsiella species and Citrobacter koseri strains was more homogeneous and generally higher than that in most of the Escherichia coli isolates studied. Our results improve the understanding of the diversity of colibactin determinants and its expression level, and may contribute to risk assessment of colibactin-producing enterobacteria.
Published: 2021

37. Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects, skeletal abnormalities, and immune dysregulation

Author: Karine Duroure, Estelle Colin, Thomas Edouard, Ludovic Martin, Linda Grimaud, Lyndon Gallacher, George McGillivray, Guy Lenaers, Valérie Desquiret-Dumas, Clarisse Billon, Anne Breton, Mohammed Zarhrate, Emmanuel Mas, Dominique Bonneau, Lynn Pais, Daniel Henrion, Thomas Haaf, Reza Maroofian, Marianna Parlato, Frank M. Ruemmele, Anne-Laure Guihot, Anaïs Philippe, Ehsan Ghayoor Karimiani, Pauline E. Schneeberger, Stanislas Lyonnet, Bernadette Bègue, Bruno Moulin, Rémi Duclaux-Loras, Nicolas Cagnard, Michael Frank, Laurence Faivre, Ruben Attali, Yves Alembik, Filippo Del Bene, Kerstin Kutsche, Céline Revenu, Fabienne Charbit-Henrion, Katta M. Girisha, Aboulfazl Rad, Eyal Reinstein, Shalini S. Nayak, Barbara Vona, Nadine Cerf-Bensussan, Caroline Lekszas, Shay Tzur, Alban Ziegler, Susan M. White, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ingénierie Radioprotection Sûreté Démantèlement (IRSD), Centre National de la Recherche Scientifique (CNRS), Geroscience and rejuvenation research center (RESTORE), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Embryology and genetics of human malformation, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de Hautepierre [Strasbourg], Nouvel Hôpital Civil de Strasbourg, Tel Aviv University (TAU), Emedgene Technologies [Tel Aviv], Murdoch Children's Research Institute (MCRI), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Kasturba Medical College, Manipal, Massachusetts Institute of Technology (MIT), University College of London [London] (UCL), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, St George's, University of London, University of Würzburg = Universität Würzburg, Fondation Princesse Grace, Fondation Maladies Rares, Harbig Family Foundation, Royal Children's Hospital Foundation, University of Tubingen (2545-1-0), Federal Ministry of Education and Research (01DQ17003 to K.K.), Indian Council of Medical Research (file no. 5/7/1508/2016 to K.M.G), National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung, and Blood Institute grant UM1 HG008900, National Human Genome Research Institute grant R01 HG009141, Victorian Government's Operational Infrastructure Support Program, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-IAHU-0001,FOReSIGHT,Enabling Vision Restoration(2018), European Project: 661527,H2020,H2020-MSCA-IF-2014,NMJALS(2015), European Project: 339407,EC:FP7:ERC,ERC-2013-ADG,IMMUNOBIOTA(2014), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Embryology and genetics of human malformation (Equipe Inserm U1163), SEGUIN, Nathalie, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Enabling Vision Restoration - - FOReSIGHT2018 - ANR-18-IAHU-0001 - IAHU - VALID, In vivo analysis of neuromuscular junction stability in zebrafish models of amyotrophic lateral sclerosis - NMJALS - - H20202015-11-16 - 2017-11-15 - 661527 - VALID, Host-microbiota interactions across the gut immune system:lessons from early onset inflammatory bowel diseases and from gnotobiotic mice - IMMUNOBIOTA - - EC:FP7:ERC2014-03-01 - 2019-02-28 - 339407 - VALID, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Connective Tissue Disorder, Loss of Heterozygosity, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, IPO8, TGF-β signaling, Pathogenesis, 0302 clinical medicine, Loss of Function Mutation, Transforming Growth Factor beta, connective tissue disorder, Child, Connective Tissue Diseases, Zebrafish, Genetics (clinical), Karyopherin, chemistry.chemical_classification, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunity, Cellular, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Middle Aged, beta Karyopherins, Pedigree, arterial dilatation, Cell biology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Phenotype, medicine.anatomical_structure, Cardiovascular Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Bone Diseases, Signal Transduction, Adult, Adolescent, Connective tissue, Biology, Importin 8, Young Adult, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Report, Genetics, medicine, Animals, Humans, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Infant, Immune dysregulation, Loeys-Dietz syndrome, biology.organism_classification, joint hyperlaxity, chemistry, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Transforming growth factor
Abstract: International audience; Dysregulated transforming growth factor TGF-beta signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-beta-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-beta signaling, ipo8(-/-) zebrafish presented mild to severe dorso-ventral patterning defects during early embryonic development. Moreover, ipo8(-/-) zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype. Our work thus provides evidence that IPO8 plays a critical and non-redundant role in TGF-beta signaling during development and reinforces the existing link between TGF-beta signaling and connective tissue defects.
Published: 2021

38. PGI 2 Inhibits Intestinal Epithelial Permeability and Apoptosis to Alleviate Colitis

Author: Camille Pochard, Anne Jarry, Guillaume Meurette, Maxime M. Mahe, Nicolas Cenac, Juliette Podevin, Emmanuel Coron, Michel Neunlist, Arnaud Bourreille, Malvyne Rolli-Derkinderen, Anne Bessard, Jacques Gonzales, The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre hospitalier universitaire de Nantes (CHU Nantes), Toulouse INSERM Metatoul-Lipidomique Core Facility-MetaboHub, the GIS-IBiSA program, the CIC 1413, the CCDE, and the Department of Pathological Anatomy and Cytology of the Hôtel-Dieu-Nantes hospital, SanteDige Foundation, GIS-IBiSA program, CIC 1413, the CCDE, and Department of Pathological Anatomy and Cytology of Hôtel-Dieu-Nantes hospital, ANR-19-CE14-0023,TACI,Ciblage de l'AMPK pour le contrôle la barrière épithéliale intestinale(2019), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), SEGUIN, Nathalie, and Ciblage de l'AMPK pour le contrôle la barrière épithéliale intestinale - - TACI2019 - ANR-19-CE14-0023 - AAPG2019 - VALID
Subjects: Male, 0301 basic medicine, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], RC799-869, Occludin, DAI, Disease Activity Index, IEC, intestinal epithelial cell, Pathogenesis, Mice, 0302 clinical medicine, MLC, myosin light chain, Intestinal mucosa, Omega-6 (n-6), Medicine, Intestinal Mucosa, ANOVA, analysis of variance, Original Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, IBD, inflammatory bowel disease, medicine.diagnostic_test, Dextran Sulfate, Gastroenterology, HRP, horseradish peroxidase, Diseases of the digestive system. Gastroenterology, Middle Aged, GI, gastrointestinal, Colitis, Ulcerative colitis, 15-HETE, 15-hydroxyeicosatetraenoic acid, 3. Good health, Caspase-3, Fatty Acids, Unsaturated, ZO-1, zonula occludens, Female, 030211 gastroenterology & hepatology, UHA, unhealthy area, medicine.symptom, IEB, intestinal epithelial barrier, PGI2, Adult, HA, healthy area, PCNA, proliferating cell nuclear antigen, IBD, PBS, phosphate-buffered saline, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, SEM, standard error of the mean, Permeability, TEER, transepithelial electrical resistance, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, DSS, dextran sulfate sodium, PUFA, polyunsaturated fatty acid, Biopsy, CD, Crohn’s disease, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Metabolomics, IFN, interferon, PG, prostaglandin, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, Tight Junction Proteins, Intestinal permeability, Hepatology, business.industry, qPCR, real-time quantitative polymerase chain reaction, Lipidomic, Inflammatory Bowel Diseases, medicine.disease, IP, prostaglandin I2 receptor, Epoprostenol, digestive system diseases, IL, interleukin, Mice, Inbred C57BL, UC, ulcerative colitis, Disease Models, Animal, Human Mucosa, 030104 developmental biology, Case-Control Studies, Cancer research, Caco-2 Cells, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background & Aims Inflammatory bowel diseases (IBDs) that encompass both ulcerative colitis and Crohn’s disease are a major public health problem with an etiology that has not been fully elucidated. There is a need to improve disease outcomes and preventive measures by developing new effective and lasting treatments. Although polyunsaturated fatty acid metabolites play an important role in the pathogenesis of several disorders, their contribution to IBD is yet to be understood. Methods Polyunsaturated fatty acids metabolite profiles were established from biopsy samples obtained from Crohn’s disease, ulcerative colitis, or control patients. The impact of a prostaglandin I2 (PGI2) analog on intestinal epithelial permeability was tested in vitro using Caco-2 cells and ex vivo using human or mouse explants. In addition, mice were treated with PGI2 to observe dextran sulfate sodium (DSS)-induced colitis. Tight junction protein expression, subcellular location, and apoptosis were measured in the different models by immunohistochemistry and Western blotting. Results A significant reduction of PGI2 in IBD patient biopsies was identified. PGI2 treatment reduced colonic inflammation, increased occludin expression, decreased caspase-3 cleavage and intestinal permeability, and prevented colitis development in DSS-induced mice. Using colonic explants from mouse and human control subjects, the staurosporine-induced increase in paracellular permeability was prevented by PGI2. PGI2 also induced the membrane location of occludin and reduced the permeability observed in colonic biopsies from IBD patients. Conclusions The present study identified a PGI2 defect in the intestinal mucosa of IBD patients and demonstrated its protective role during colitis., Graphical abstract
Published: 2021

39. Convergent Rewiring of the Virulence Regulatory Network Promotes Adaptation of Ralstonia solanacearum on Resistant Tomato

Author: Gopalan-Nair, Rekha, Jardinaud, Marie-Françoise, Legrand, Ludovic, Landry, David, Barlet, Xavier, Lopez-Roques, Céline, Vandecasteele, Céline, Bouchez, Olivier, Genin, Stéphane, Guidot, Alice, Laboratoire des Interactions Plantes Microbes Environnement (LIPME), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French Research Federation 'FR AIB' (Agrobiosciences Interactions and Biodiversity), GET-PACBIO program (Programme Operationnel FEDER-FSE MIDI-PYRENEES ET GARONNE 2014-2020), ANR-11-IDEX-0002,UNITI,Université Fédérale de Toulouse(2011), ANR-17-CE20-0005,EPI-PATH,Rôle des modifications épigénétiques chez un pathogène de plante au cours de l'adaptation à l'hôte et des changements d'hôte(2017), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), SEGUIN, Nathalie, Initiative d'excellence - Université Fédérale de Toulouse - - UNITI2011 - ANR-11-IDEX-0002 - IDEX - VALID, Rôle des modifications épigénétiques chez un pathogène de plante au cours de l'adaptation à l'hôte et des changements d'hôte - - EPI-PATH2017 - ANR-17-CE20-0005 - AAPG2017 - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, bacterial plant pathogen, Adaptation, Biological, [SDV.GEN] Life Sciences [q-bio]/Genetics, AcademicSubjects/SCI01180, Regulon, [SDV.BV.BOT] Life Sciences [q-bio]/Vegetal Biology/Botanics, Solanum lycopersicum, transcriptomic variation, adaptive potential, genomic polymorphisms, experimental evolution, Discoveries, [SDV.GEN]Life Sciences [q-bio]/Genetics, AcademicSubjects/SCI01130, food and beverages, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, fitness measure, Biological Evolution, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Gain of Function Mutation, Ralstonia solanacearum, Genetic Fitness, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Transcriptome
Abstract: International audience; Abstract The evolutionary and adaptive potential of a pathogen is a key determinant for successful host colonization and proliferation but remains poorly known for most of the pathogens. Here, we used experimental evolution combined with phenotyping, genomics, and transcriptomics to estimate the adaptive potential of the bacterial plant pathogen Ralstonia solanacearum to overcome the quantitative resistance of the tomato cultivar Hawaii 7996. After serial passaging over 300 generations, we observed pathogen adaptation to within-plant environment of the resistant cultivar but no plant resistance breakdown. Genomic sequence analysis of the adapted clones revealed few genetic alterations, but we provide evidence that all but one were gain of function mutations. Transcriptomic analyses revealed that even if different adaptive events occurred in independently evolved clones, there is convergence toward a global rewiring of the virulence regulatory network as evidenced by largely overlapping gene expression profiles. A subset of four transcription regulators, including HrpB, the activator of the type 3 secretion system regulon and EfpR, a global regulator of virulence and metabolic functions, emerged as key nodes of this regulatory network that are frequently targeted to redirect the pathogen’s physiology and improve its fitness in adverse conditions. Significant transcriptomic variations were also detected in evolved clones showing no genomic polymorphism, suggesting that epigenetic modifications regulate expression of some of the virulence network components and play a major role in adaptation as well.
Published: 2021

40. Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis

Author: Turpin, Chloé, Catan, Aurélie, Meilhac, Olivier, Bourdon, Emmanuel, Canonne-Hergaux, François, Rondeau, Philippe, Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ministère de l’Enseignement Supérieur et de la Recherche, Université de La Réunion, European Regional Development Funds : RE0001897, the Structure fédérative de recherche biosécurité en milieu tropical (BIOST), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and SEGUIN, Nathalie
Subjects: Erythrocytes, Meilhac, QH301-705.5, Rondeau, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Review, Heme, O, Hemolysis, C, Hemoglobins, iron, A, eryptosis, E, Animals, Humans, Turpin, Biology (General), [SDV.BC] Life Sciences [q-bio]/Cellular Biology, QD1-999, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Erythrocyte Membrane, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Atherosclerosis, Bourdon, erythrophagocytosis, haemoglobin, Canonne-Hergaux, Chemistry, Oxidative Stress, F, Cytophagocytosis, Catan, glycation, Disease Progression, Disease Susceptibility, P atherosclerosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers
Abstract: International audience; The development and progression of atherosclerosis (ATH) involves lipid accumulation, oxidative stress and both vascular and blood cell dysfunction. Erythrocytes, the main circulating cells in the body, exert determinant roles in the gas transport between tissues. Erythrocytes have long been considered as simple bystanders in cardiovascular diseases, including ATH. This review highlights recent knowledge concerning the role of erythrocytes being more than just passive gas carriers, as potent contributors to atherosclerotic plaque progression. Erythrocyte physiology and ATH pathology is first described. Then, a specific chapter delineates the numerous links between erythrocytes and atherogenesis. In particular, we discuss the impact of extravasated erythrocytes in plaque iron homeostasis with potential pathological consequences. Hyperglycaemia is recognised as a significant aggravating contributor to the development of ATH. Then, a special focus is made on glycoxidative modifications of erythrocytes and their role in ATH. This chapter includes recent data proposing glycoxidised erythrocytes as putative contributors to enhanced atherothrombosis in diabetic patients.
Published: 2021

41. Healthy Aging Biomarkers: The INSPIRE's Contribution

Author: Vergnolle, Nathalie, Ader, Isabelle, Penicaud, Luc, Raymond Letron, Isabelle, Andrieu, Sandrine, Rolland, Julien Yves, Barreto De Souto, Philippe, Vellas, Bruno, Guyonnet, Sophie, Beard, J.R., Parini, Angelo, Davezac, Noélie, Dray, Cédric, Gourdy, P., Rampon, Claire, Valet, Phillippe, Fazilleau, Nicolas, Payoux, Pierre, Sierra, Felipe, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Geroscience and rejuvenation research center (RESTORE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Gérontopôle, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], University of New South Wales [Sydney] (UNSW), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut du Vieillissement, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Region Occitanie/Pyrenees-Mediterranee (Reference number: 1901175), European Regional Development Fund (ERDF) (Project number: MP0022856), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), and SEGUIN, Nathalie
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, healthy aging, frailty, dependence, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology
Abstract: International audience; The find solutions for optimizing healthy aging and increase health span is one of the main challenges for our society. A novel healthcare model based on integration and a shift on research and care towards the maintenance of optimal functional levels are now seen as priorities by the WHO. To address this issue, an integrative global strategy mixing longitudinal and experimental cohorts with an innovative transverse understanding of physiological functioning is missing. While the current approach to the biology of aging is mainly focused on parenchymal cells, we propose that age-related loss of function is largely determined by three elements which constitute the general ground supporting the different specific parenchyma: i.e. the stroma, the immune system and metabolism. Such strategy that is implemented in INSPIRE projects can strongly help to find a composite biomarker capable of predicting changes in capacity across the life course with thresholds signalling frailty and care dependence.
Published: 2021

42. Crohn’s disease: is the cold chain hypothesis still hot?

Author: Frédérick Barreau, Anne Dumay, Jean-Pierre Hugot, Ulrich Meinzer, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sorbonne Paris Cite, ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-11-IDEX-0005,EFL,Empirical Foundations of Linguistics : data, methods, models(2011), SEGUIN, Nathalie, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Crohn’s disease, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Disease, Review Article, Yersinia, Working hypothesis, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, Refrigeration, Causality chain, exclusion diet, 0303 health sciences, Crohn's disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, mesenteric lymph nodes, Gastroenterology, General Medicine, refrigeration, 3. Good health, macrophages, Causality, food products, 030211 gastroenterology & hepatology, gut inflammation, autophagy, 03 medical and health sciences, Immune system, Elimination diet, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, enteral nutrition, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, AcademicSubjects/MED00260, business.industry, mucosal immune response, biology.organism_classification, medicine.disease, cold, plague, Immunology, Etiology, Food Microbiology, creeping fat, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Crohn’s disease [CD] is an inflammatory bowel disease of unknown aetiology. During recent decades, significant technological advances led to development of -omic datasets allowing a detailed description of the disease. Unfortunately these have not, to date, resolved the question of the aetiology of CD. Thus, it may be necessary to [re]consider hypothesis-driven approaches to resolve the aetiology of CD. According to the cold chain hypothesis, the development of industrial and domestic refrigeration has led to frequent exposure of human populations to bacteria capable of growing in the cold. These bacteria, at low levels of exposure, particularly those of the genus Yersinia, are believed to be capable of inducing exacerbated inflammation of the intestine in genetically predisposed subjects. We discuss the consistency of this working hypothesis in light of recent data from epidemiological, clinical, pathological, microbiological, and molecular studies.
Published: 2021

43. Colon Fibroblasts and Inflammation: Sparring Partners in Colorectal Cancer Initiation?

Author: Laurent Malaquin, Lauriane Onfroy-Roy, Audrey Ferrand, Dimitri Hamel, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Équipe Ingénierie pour les sciences du vivant (LAAS-ELIA), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Plan Cancer 'System biology' 2017, European Project: 760927,H2020-HoliFAB project, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, SEGUIN, Nathalie, HoliFAB - H2020-HoliFAB project - 760927 - INCOMING, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse Capitole (UT Capitole)
Subjects: 0301 basic medicine, Surgical resection, Cancer Research, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Colorectal cancer, Malaquin, Inflammation, colorectal cancer, Review, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Stroma, fibroblasts, medicine, stroma, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Onfroy-Roy, Colon crypt, intestinal stem cells, Hamel, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, colon, business.industry, A. Colon Fibroblasts and Inflammation: colon, Inflammatory Bowel Diseases, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, digestive system diseases, L, 3. Good health, 030104 developmental biology, Oncology, inflammation, Ferrand, 030220 oncology & carcinogenesis, D, Cancer research, medicine.symptom, business, Homeostasis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Simple Summary Colorectal cancer (CRC) is the third most common cause of cancer-related death. Patients suffering inflammatory bowel disease have an increased risk of CRC. It is admitted that CRC found its origin within crypts of the colon mucosa, which host the intestinal stem cells (ISCs) responsible of the tissue renewal. ISC behavior is controlled by the fibroblasts that surround the crypt. During inflammation, the signals delivered by fibroblasts are altered, leading to stem cells’ dysregulation, possibly turning them into cancer-initiating cells. Here, we reviewed the interplays between the fibroblast and the ISCs, possibly leading to the initiation of CRC due to chronic inflammation. Abstract Colorectal cancer (CRC) is the third most common cause of cancer-related death. Significant improvements in CRC treatment have been made for the last 20 years, on one hand thanks to a better detection, allowing surgical resection of the incriminated area, and on the other hand, thanks to a better knowledge of CRC’s development allowing the improvement of drug strategies. Despite this crucial progress, CRC remains a public health issue. The current model for CRC initiation and progression is based on accumulation of sequential known genetic mutations in the colon epithelial cells’ genome leading to a loss of control over proliferation and survival. However, increasing evidence reveals that CRC initiation is more complex. Indeed, chronic inflammatory contexts, such as inflammatory bowel diseases, have been shown to increase the risk for CRC development in mice and humans. In this manuscript, we review whether colon fibroblasts can go from the main regulators of the ISC homeostasis, regulating not only the renewal process but also the epithelial cells’ differentiation occurring along the colon crypt, to the main player in the initiation of the colorectal cancer process due to chronic inflammation.
Published: 2021

44. Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammation

Author: Perrine Rousset, Laurent Alric, Anissa Edir, Chrystelle Bonnart, Jean-Paul Motta, Céline Deraison, David Sagnat, Elena F. Verdu, Derek M. McKay, Corinne Rolland, Emmanuel Mas, Laura Guiraud, Delphine Bonnet, Nathalie Vergnolle, Muriel Quaranta-Nicaise, Etienne Buscail, Ana Carolina Rodrigues Florence, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], McMaster University [Hamilton, Ontario], University of Calgary, ANR JCJC-11JSV1 001 01, AOL-MICILIP project, ANR-12-BSV1-0030,ELAPROB-IBD,Mecanismes d'action des probiotiques recombinants pour l'Elafine: Leur utilisation possible pour traiter les maladies inflammatoires chroniques de l'intestin?(2012), ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), European Project: 627487,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IOF,EPIMACASE(2014), European Project: 310973,EC:FP7:ERC,ERC-2012-StG_20111109,PIPE(2013), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), SEGUIN, Nathalie, BLANC - Mecanismes d'action des probiotiques recombinants pour l'Elafine: Leur utilisation possible pour traiter les maladies inflammatoires chroniques de l'intestin? - - ELAPROB-IBD2012 - ANR-12-BSV1-0030 - BLANC - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, THE ROLE OF ELASTASE/ELASTASE INHIBITOR IN DIALOG BETWEEN INTESTINAL EPITHELIAL CELLS AND MACROPHAGES IN INFLAMMATORY BOWEL DISEASES CONTEXT - EPIMACASE - - EC:FP7:PEOPLE2014-08-06 - 2016-08-05 - 627487 - VALID, and Physiology of the Intestine: Proteases from the Epithelium - PIPE - - EC:FP7:ERC2013-04-01 - 2018-03-31 - 310973 - VALID
Subjects: 0301 basic medicine, Adult, Male, Proteases, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Colon, medicine.medical_treatment, Immunology, Inflammation, Disease, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Inflammatory bowel disease, Article, Tight Junctions, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Immunology and Allergy, Medicine, Humans, Intestinal Mucosa, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Immunity, Mucosal, Barrier function, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Elastase, Middle Aged, medicine.disease, Inflammatory Bowel Diseases, Pathophysiology, digestive system diseases, 3. Good health, Up-Regulation, 030104 developmental biology, Cytokine, Cytokines, 030211 gastroenterology & hepatology, Female, medicine.symptom, Inflammation Mediators, business, Leukocyte Elastase, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Imbalance between proteases and their inhibitors plays a crucial role in the development of Inflammatory Bowel Diseases (IBD). Increased elastolytic activity is observed in the colon of patients suffering from IBD. Here, we aimed at identifying the players involved in elastolytic hyperactivity associated with IBD and their contribution to the disease. We revealed that epithelial cells are a major source of elastolytic activity in healthy human colonic tissues and this activity is greatly increased in IBD patients, both in diseased and distant sites of inflammation. This study identified a previously unrevealed production of elastase 2A (ELA2A) by colonic epithelial cells, which was enhanced in IBD patients. We demonstrated that ELA2A hyperactivity is sufficient to lead to a leaky epithelial barrier. Epithelial ELA2A hyperactivity also modified the cytokine gene expression profile with an increase of pro-inflammatory cytokine transcripts, while reducing the expression of pro-resolving and repair factor genes. ELA2A thus appears as a novel actor produced by intestinal epithelial cells, which can drive inflammation and loss of barrier function, two essentials pathophysiological hallmarks of IBD. Targeting ELA2A hyperactivity should thus be considered as a potential target for IBD treatment.
Published: 2021

45. Perineal Wound Closure Following Abdominoperineal Resection and Pelvic Exenteration for Cancer: A Systematic Review and Meta-Analysis

Author: Cindy Canivet, Nicolas Carrere, Benoit Chaput, Emilie Bérard, Jason Shourick, Etienne Buscail, Antoine Philis, Louis Buscail, Jean-Pierre Duffas, Laurent Ghouti, Elodie Chantalat, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), SEGUIN, Nathalie, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Cancer Research, Colorectal cancer, medicine.medical_treatment, Ghouti, Shourick, 030230 surgery, Group B, perineal wound healing, 0302 clinical medicine, A, E, Major complication, abdominoperineal resection, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, perineal morbidity, Abdominoperineal resection, et al. Perineal Wound Closure Following Abdominoperineal Resection and Pelvic Exenteration for Cancer: A Systematic Review and rectal cancer, J.-P, Philis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, L, Buscail, Chantalat, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Meta-analysis, Canivet, medicine.medical_specialty, lcsh:RC254-282, C, surgical oncology, 03 medical and health sciences, FlapMesh, Perineal wound, medicine, rectal cancer, Pelvic exenteration, Carrere, business.industry, J, Cancer, N, medicine.disease, Duffas, Surgery, mesh, Berard, Systematic Review, business, flap, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Simple Summary Abdominoperineal resection (APR) and pelvic exenteration (PE) for the treatment of cancer (mainly anal and rectal cancers) require extensive pelvic resection with a high rate of postoperative complications. The objective of this work was to systematically review and meta-analyze the effects of vertical rectus abdominis myocutaneous flap (VRAMf) and mesh closure on perineal morbidity following APR and PE. The studies were distributed as follows: Group A comparing primary closure (PC) and VRAMf, Group B comparing PC and mesh closure, Group C comparing PC and VRAMf in PE. The meta-analysis of Groups A and B showed PC to be associated with an increase in the rate of total and major perineal wound complications. PC was associated with a decrease in total and major perineal complications in Group C. Abstract Background. Abdominoperineal resection (APR) and pelvic exenteration (PE) for the treatment of cancer require extensive pelvic resection with a high rate of postoperative complications. The objective of this work was to systematically review and meta-analyze the effects of vertical rectus abdominis myocutaneous flap (VRAMf) and mesh closure on perineal morbidity following APR and PE (mainly for anal and rectal cancers). Methods. We searched PubMed, Cochrane, and EMBASE for eligible studies as of the year 2000. After data extraction, a meta-analysis was performed to compare perineal wound morbidity. The studies were distributed as follows: Group A comparing primary closure (PC) and VRAMf, Group B comparing PC and mesh closure, and Group C comparing PC and VRAMf in PE. Results. Our systematic review yielded 18 eligible studies involving 2180 patients (1206 primary closures, 647 flap closures, 327 mesh closures). The meta-analysis of Groups A and B showed PC to be associated with an increase in the rate of total (Group A: OR 0.55, 95% CI 0.43–0.71; p < 0.01/Group B: OR 0.54, CI 0.17–1.68; p = 0.18) and major perineal wound complications (Group A: OR 0.49, 95% CI 0.35–0.68; p < 0.001/Group B: OR 0.38, 95% CI 0.12–1.17; p < 0.01). PC was associated with a decrease in total (OR 2.46, 95% CI 1.39–4.35; p < 0.01) and major (OR 1.67, 95% CI 0.90–3.08; p = 0.1) perineal complications in Group C. Conclusions. Our results confirm the contribution of the VRAMf in reducing major complications in APR. Similarly, biological prostheses offer an interesting alternative in pelvic reconstruction. For PE, an adapted reconstruction must be proposed with specialized expertise.
Published: 2021

46. The INSPIRE bio-resource research platform for healthy aging and geroscience: focus on the human translational research cohort (the INSPIRE-t cohort)

Author: Yves Rolland, Sandrine Andrieu, Philippe Valet, P. de Souto Barreto, Pierre Gourdy, Sophie Guyonnet, Nicolas Fazilleau, Isabelle Ader, Claire Rampon, Louis Casteilla, Luc Pénicaud, Noélie Davezac, Angelo Parini, C. Takeda, Roland S. Liblau, Pierre-Jean Ousset, Pierre Payoux, Cédric Dray, Nathalie Vergnolle, Bruno Vellas, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gérontopôle, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), STROMALab, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toulouse Neuro Imaging Center (ToNIC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Institut de Recherche en Santé Digestive (IRSD ), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), The Region Auvergne-Rhone-Alpes, Region Bourgogne-Franche-Comte,Region Hauts-de-France,Region Nouvelle-Aquitaine (1901175), the European Regional Development Fund (ERDF) (Project number: MP0022856), MSD Avenir, Inspire Chairs of Excellence - Alzheimer Prevention in Occitania and Catalonia (APOC), EDENIS, KORIAN, Pfizer, Pierre-Fabre, European Project: ERDF, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), SEGUIN, Nathalie, and European Regional Development Fund - ERDF - INCOMING
Subjects: 0301 basic medicine, Gerontology, [SDV]Life Sciences [q-bio], MESH: Geriatrics, Cohort Studies, Healthy Aging, Translational Research, Biomedical, 0302 clinical medicine, MESH: Aged, 80 and over, biology of aging, Health care, Medicine, MESH: Cohort Studies, Biological Specimen Banks, Original Research, integrated care, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Geroscience, MESH: Biological Specimen Banks, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, MESH: Healthy Aging, General Medicine, Middle Aged, Biobank, 3. Good health, [SDV] Life Sciences [q-bio], biological aging, Cohort, Population study, France, MESH: Translational Research, Biomedical, Adult, Gerosciences, Translational research, 03 medical and health sciences, Humans, intrinsic capacity, Aged, MESH: Humans, business.industry, MESH: Adult, Integrated care, MESH: France, 030104 developmental biology, Geriatrics, translational research on aging, business, 030217 neurology & neurosurgery, Blood sampling
Abstract: International audience; Background : The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. Objectives : The main objective of the INStitute for Prevention healthy aging and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans.Methods : The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up.Expected Results : Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.Electronic Supplementary Material.Supplementary material : is available for this article at 10.14283/jfa.2020.38 and is accessible for authorized users.
Published: 2021

47. Gastrointestinal Perspective of Coronavirus Disease 2019 in Children-An Updated Review

Author: Christos Tzivinikos, Javier Martín de Carpi, Emmanuel Mas, Jernej Dolinsek, Mike Thomson, Marco Deganello Saccomani, Ilse Broekaert, Erasmo Miele, Amit Assa, Osvaldo Borrelli, Marc A. Benninga, Assa, Amit, Benninga, Marc A, Borrelli, Osvaldo, Broekaert, Ilse, de Carpi, Javier Martin, Saccomani, Marco Deganello, Dolinsek, Jernej, Mas, Emmanuel, Miele, Erasmo, Thomson, Mike, Tzivinikos, Christos, Ben-Gurion University of the Negev (BGU), University of Amsterdam [Amsterdam] (UvA), Great Ormond Street Hospital for Children [London] (GOSH), University Hospital of Cologne [Cologne], University of Barcelona, University of Verona (UNIVR), University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, Università degli studi di Verona = University of Verona (UNIVR), and SEGUIN, Nathalie
Subjects: Diarrhea, Abdominal pain, paediatric, Gastrointestinal Diseases, medicine.medical_treatment, coronavirus, Peritonitis, Review Article, Liver transplantation, Inflammatory bowel disease, gastrointestinal manifestations, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Immune system, 030225 pediatrics, Medicine, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, SARS-CoV-2, Gastroenterology, COVID-19, medicine.disease, Systemic Inflammatory Response Syndrome, 3. Good health, Systemic inflammatory response syndrome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pediatrics, Perinatology and Child Health, Immunology, multisystem inflammatory disease, Pancreatitis, 030211 gastroenterology & hepatology, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Gastrointestinal symptoms are common findings in children with severe acute respiratory syndrome coronavirus 2 infection, including vomiting, diarrhoea, abdominal pain, and difficulty in feeding, although these symptoms tend to be mild. The hepato-biliary system and the pancreas may also be involved, usually with a mild elevation of transaminases and, rarely, pancreatitis. In contrast, a late hyper-inflammatory phenomenon, termed multisystem inflammatory syndrome (MIS-C), is characterized by more frequent gastrointestinal manifestations with greater severity, sometimes presenting as peritonitis. Gastrointestinal and hepato-biliary manifestations are probably related to a loss in enterocyte absorption capability and microscopic mucosal damage caused by a viral infection of intestinal epithelial cells, hepatocytes and other cells through the angiotensin conversion enzyme 2 receptor resulting in immune cells activation with subsequent release of inflammatory cytokines. Specific conditions such as inflammatory bowel disease (IBD) and liver transplantation may pose a risk for the more severe presentation of coronavirus disease 2019 (COVID-19) but as adult data accumulate, paediatric data is still limited. The aim of this review is to summarize the current evidence about the effect of COVID-19 on the gastrointestinal system in children, with emphasis on the emerging MIS-C and specific considerations such as patients with IBD and liver transplant recipients.
Published: 2021

48. Differentiating iron-loading anemias using a newly developed and analytically validated ELISA for human serum erythroferrone

Author: Rachel P. L. van Swelm, Dorine W. Swinkels, Laura E. Diepeveen, Léon Kautz, Rian Roelofs, Nicolai Grebenchtchikov, Radboud university [Nijmegen], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), E.C. Noyons foundation, Radboud University [Nijmegen], and SEGUIN, Nathalie
Subjects: Male, 0301 basic medicine, Ineffective erythropoiesis, Erythroblasts, Physiology, Peptide Hormones, medicine.disease_cause, Matrix (chemical analysis), Mathematical and Statistical Techniques, 0302 clinical medicine, Sideroblastic anemia, Animal Cells, Red Blood Cells, Medicine and Health Sciences, Erythropoiesis, Enzyme-Linked Immunoassays, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, biology, Chemistry, Statistics, Drugs, food and beverages, Anemia, Hematology, Middle Aged, Erythroferrone, Body Fluids, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, Blood, Physical Sciences, Regression Analysis, Cytokines, Medicine, Female, Anatomy, Cellular Types, Research Article, Adult, Analyte, Iron Overload, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Iron, Science, Bone Marrow Cells, Enzyme-Linked Immunosorbent Assay, Linear Regression Analysis, Research and Analysis Methods, Blood Plasma, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Hepcidins, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Hepcidin, medicine, Humans, Statistical Methods, Immunoassays, Aged, Pharmacology, Blood Cells, Heparin, beta-Thalassemia, fungi, Biology and Life Sciences, Cell Biology, medicine.disease, Molecular biology, Hematopoiesis, Anemia, Sideroblastic, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], 030104 developmental biology, Polyclonal antibodies, Immunologic Techniques, biology.protein, Physiological Processes, Mathematics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Erythroferrone (ERFE), the erythroid regulator of iron metabolism, inhibits hepcidin to increase iron availability for erythropoiesis. ERFE plays a pathological role during ineffective erythropoiesis as occurs in X-linked sideroblastic anemia (XLSA) and β-thalassemia. Its measurement might serve as an indicator of severity for these diseases. However, for reliable quantification of ERFE analytical characterization is indispensable to determine the assay’s limitations and define proper methodology. We developed a sandwich ELISA for human serum ERFE using polyclonal antibodies and report its extensive analytical validation. This new assay showed, for the first time, the differentiation of XLSA and β-thalassemia major patients from healthy controls (p = 0.03) and from each other (p2 = 0.83). Nevertheless, employment of one optimal dilution of all serum samples is warranted to obtain reliable results. When adequately performed, the assay can be used to further unravel the human erythropoiesis-hepcidin-iron axis in various disorders and assess the added diagnostic value of ERFE.
Published: 2021

49. The Polyphosphate Kinase of Escherichia coli Is Required for Full Production of the Genotoxin Colibactin

Author: Min Tang-Fichaux, Camille V. Chagneau, Nadège Bossuet-Greif, Jean-Philippe Nougayrède, Éric Oswald, Priscilla Branchu, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-17-CE35-0010,UTI-TOUL,Récentes avancées dans la pathogénicité de Escherichia coli : nouvelles cibles pour des approches antivirulence et immunomodulation dans les infections urinaires(2017), SEGUIN, Nathalie, and Récentes avancées dans la pathogénicité de Escherichia coli : nouvelles cibles pour des approches antivirulence et immunomodulation dans les infections urinaires - - UTI-TOUL2017 - ANR-17-CE35-0010 - AAPG2017 - VALID
Subjects: Molecular Biology and Physiology, Carcinogenesis, PPK, pks, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Microbiology, mesalamine, Escherichia coli, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Phosphotransferases (Phosphate Group Acceptor), Virulence, Escherichia coli Proteins, genotoxicity, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, QR1-502, Polyketides, Colonic Neoplasms, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, colibactin, Peptides, DNA Damage, HeLa Cells, Mutagens, Research Article
Abstract: Colibactin-producing E. coli induces DNA damage in eukaryotic cells and promotes tumor formation in mouse models of intestinal inflammation. Recent studies have provided strong evidence supporting the causative role of colibactin in human colorectal cancer (CRC) progression., Colibactin induces DNA damage in mammalian cells and has been linked to the virulence of Escherichia coli and the promotion of colorectal cancer (CRC). By looking for mutants attenuated in the promoter activity of clbB encoding one of the key enzymes for the production of colibactin, we found that a mutant of the gene coding for the polyphosphate kinase (PPK) produced less colibactin than the parental strain. We observed this phenotype in different strains ranging from pathogens responsible for meningitis, urinary tract infection, or mouse colon carcinogenesis to the probiotic Nissle 1917. We confirmed the role of PPK by using an inhibitor of PPK enzymatic activity, mesalamine (also known as 5-aminosalicylic acid). Interestingly, mesalamine has a local anti-inflammatory effect on the epithelial cells of the colon and is used to treat inflammatory bowel disease (IBD). Upon treatment with mesalamine, a decreased genotoxicity of colibactin-producing E. coli was observed both on epithelial cells and directly on purified DNA. This demonstrates the direct effect of mesalamine on bacteria independently from its anti-inflammatory effect on eukaryotic cells. Our results suggest that the mechanisms of action of mesalamine in treating IBD and preventing CRC could also lie in the inhibition of colibactin production. All in all, we demonstrate that PPK is required for the promoter activity of clbB and the production of colibactin, which suggests that PPK is a promising target for the development of anticolibactin and antivirulence strategies. IMPORTANCE Colibactin-producing E. coli induces DNA damage in eukaryotic cells and promotes tumor formation in mouse models of intestinal inflammation. Recent studies have provided strong evidence supporting the causative role of colibactin in human colorectal cancer (CRC) progression. Therefore, it is important to understand the regulation of the production of this genotoxin. Here, we demonstrate that polyphosphate kinase (PPK) is required for the promoter activity of clbB and the production of colibactin. Interestingly, PPK is a multifunctional player in bacterial virulence and stress responses and has been proposed as a new target for developing antimicrobial medicine. We observed inhibition of colibactin production by using a previously identified PPK inhibitor (i.e., mesalamine, an anti-inflammatory drug commonly prescribed for inflammatory bowel diseases). These data brought us a new perspective on the regulatory network of colibactin production and provided us a clue for the development of anticolibactin strategies for CRC treatment/prophylaxis.
Published: 2020

50. Extracellular Matrix Mechanical Properties and Regulation of the Intestinal Stem Cells: When Mechanics Control Fate

Author: Audrey Ferrand, Laurent Malaquin, Dimitri Hamel, Julie Foncy, Lauriane Onfroy-Roy, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Équipe Ingénierie pour les sciences du vivant (LAAS-ELIA), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Service Instrumentation Conception Caractérisation (LAAS-I2C), Region Occitanie, Universite de Toulouse III : APR2017-405, Universite de Toulouse III : 2018-046-CIF-D-DRDV, Plan Cancer 'System biology'2017 : C18006BS, European Project: 760927,H2020-HoliFAB project, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse Capitole (UT Capitole), Université Fédérale Toulouse Midi-Pyrénées, SEGUIN, Nathalie, HoliFAB - H2020-HoliFAB project - 760927 - INCOMING, Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1)
Subjects: 0301 basic medicine, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], microfluidic, Review, [SDV.GEN] Life Sciences [q-bio]/Genetics, mechanical properties, scaffold, Epithelium, Extracellular matrix, Mice, stiffness, 0302 clinical medicine, Homeostasis, deformability, Intestinal Mucosa, Stem Cell Niche, lcsh:QH301-705.5, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Tissue Scaffolds, Stem Cells, Cell Differentiation, General Medicine, Phenotype, Cell biology, Intestines, Organoids, 030220 oncology & carcinogenesis, Stem cell, inorganic chemicals, extracellular matrix, organoid, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, digestive system, 03 medical and health sciences, topography, Organoid, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Cell Lineage, Secretion, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cell Proliferation, Inflammation, [SDV.GEN]Life Sciences [q-bio]/Genetics, colon, Regeneration (biology), Mesenchymal stem cell, fungi, Epithelial Cells, Inflammatory Bowel Diseases, 030104 developmental biology, lcsh:Biology (General), hydrogel, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Intestinal stem cells (ISC) are crucial players in colon epithelium physiology. The accurate control of their auto-renewal, proliferation and differentiation capacities provides a constant flow of regeneration, maintaining the epithelial intestinal barrier integrity. Under stress conditions, colon epithelium homeostasis in disrupted, evolving towards pathologies such as inflammatory bowel diseases or colorectal cancer. A specific environment, namely the ISC niche constituted by the surrounding mesenchymal stem cells, the factors they secrete and the extracellular matrix (ECM), tightly controls ISC homeostasis. Colon ECM exerts physical constraint on the enclosed stem cells through peculiar topography, stiffness and deformability. However, little is known on the molecular and cellular events involved in ECM regulation of the ISC phenotype and fate. To address this question, combining accurately reproduced colon ECM mechanical parameters to primary ISC cultures such as organoids is an appropriated approach. Here, we review colon ECM physical properties at physiological and pathological states and their bioengineered in vitro reproduction applications to ISC studies.
Published: 2020

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