Author: "Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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215 results on '"Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)"'

1. Anti-TNF Agents Restrict Adherent-invasive Escherichia coli Replication Within Macrophages Through Modulation of Chitinase 3-like 1 in Patients with Crohn’s Disease

Author: Clara Douadi, Emilie Vazeille, Christophe Chambon, Michel Hébraud, Margot Fargeas, Marie Dodel, Dilek Coban, Bruno Pereira, Aurélien Birer, Pierre Sauvanet, Anthony Buisson, Nicolas Barnich, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Qualité des Produits Animaux (QuaPA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and Département gastroentérologie
Subjects: Proteomics, Macrophages, [SDV]Life Sciences [q-bio], Gastroenterology, Membrane Proteins, anti-TNF, General Medicine, Bacterial Adhesion, Crohn's disease, Crohn Disease, chitinase 3-like 1, Escherichia coli, Humans, Tumor Necrosis Factor Inhibitors, Chitinase-3-Like Protein 1, Intestinal Mucosa, Escherichia coli Infections, AIEC
Abstract: Background and Aims The mechanism of action of anti-tumour necrosis factor [anti-TNF] agents could implicate macrophage modulation in Crohn’s disease [CD]. As CD macrophages are defective in controlling CD-associated adherent-invasive Escherichia coli [AIEC], anti-TNF agents could limit AIEC replication within macrophages. We assessed the effect of anti-TNF agents on AIEC survival within monocyte-derived macrophages [MDMs] from CD patients and attempted to identify the proteins involved. Methods Peripheral blood MDMs were obtained from 44 CD patients [22 with and 22 without anti-TNF agents]. MDMs were infected with reference strain AIEC-LF82. Proteomic analysis was performed before and 6 h after AIEC-LF82 infection. Results AIEC-LF82 survival was lower in MDMs from CD patients receiving anti-TNF agents compared to those who did not [−73%, p = 0.006]. After AIEC-LF82 infection, the levels of CD82 [p = 0.007], ILF3 [Interleukin enhancer-binding factor 3; p = 0.001], FLOT-1 [Flotillin-1; p = 0.007] and CHI3L1 [Chitinase 3-like 1; p = 0.035] proteins were different within CD-MDMs depending on anti-TNF exposure. FLOT-1 [ϱ = −0.44; p = 0.038] and CHI3L1 [ϱ = 0.57, p = 0.006] levels were inversely and positively correlated with AIEC survival within MDMs from CD patients with or without anti-TNF, respectively. We observed a dose-dependent decrease of AIEC-LF82 survival after adjunction of anti-TNF within MDMs, inducing an increase of FLOT-1 and decrease of CHI3L1 mRNA levels. Neutralization of intra-macrophagic CHI3L1 protein using anti-CHI3L1 antibodies reduced AIEC survival within macrophages 6 h after infection [p < 0.05]. Conclusion Anti-TNF agents are able to restrict replication of pathobionts, such as AIEC, within macrophages by modulating FLOT-1 and CHI3L1 expression in CD patients.
Published: 2022

2. Faster and less invasive tools to identify patients with ileal colonization by adherent‐invasive E. coli in Crohn's disease

Author: Clara Yzet, Anthony Buisson, Elisabeth Billard, Benjamin Pariente, Caroline Chevarin, Jérôme Filippi, Philippe Seksik, Nicolas Barnich, Laurent Peyrin-Biroulet, Gilles Bommelaer, Emilie Vazeille, Marion Goutte, Gilles Boschetti, Mathurin Fumery, Stéphane Nancey, Maria Nachury, Anaëlle Dubois, Bruno Pereira, Nathalie Ballet, Matthieu Allez, Stéphanie Rodriguez, Xavier Hébuterne, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Amiens-Picardie, CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lesaffre, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], Hôpital Claude Huriez [Lille], INRAeUSC-2018Clermont Auvergne UniversityLesaffre InternationalMinistere de la Recherche et de la TechnologieI-SITE projectCAP 2025, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, Saliva, anti-E, Biopsy, adherent‐invasive E. coli, Gastroenterology, Inflammatory bowel disease, Feces, 0302 clinical medicine, Crohn Disease, Prospective Studies, Intestinal Mucosa, 0303 health sciences, Crohn's disease, biology, medicine.diagnostic_test, Colonoscopy, Antibodies, Bacterial, CEACAM6. IBD, medicine.anatomical_structure, Oncology, Biomarker (medicine), Female, Original Article, 030211 gastroenterology & hepatology, Antibody, adherent-invasive E, medicine.medical_specialty, IBD, Ileum, 03 medical and health sciences, inflammatory bowel disease, Internal medicine, Escherichia coli, medicine, anti‐E. coli antibodies, Humans, CEACAM6, 030304 developmental biology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, coli, coli antibodies, biology.protein, business, Biomarkers
Abstract: International audience; Background and AimsThe identification of Crohn's disease (CD)-associated adherent and invasive Escherichia coli (AIEC) is time-consuming and requires ileal biopsies. We aimed to identify a faster and less invasive methods to detect ileal colonization by AIEC in CD patients.MethodsCD patients requiring ileo-colonoscopy were consecutively enrolled in this prospective multicenter study. Samples from saliva, serum, stools, and ileal biopsies of CD patients were collected.ResultsAmong 102 CD patients, the prevalence of AIEC on ileal biopsies was 24.5%. The abundance and global invasive ability of ileal-associated total E. coli were respectively ten-fold (p = 0.0065) and two-fold (p = 0.0007) higher in AIEC-positive (vs. AIEC-negative), while abundance of total E. coli in the feces was not correlated with AIEC status in the ileum. The best threshold of ileal total E. coli was 60 cfu/biopsy to detect AIEC-positive patients, with high negative predictive value (NPV) (94.1%[80.3–99.3]), while the global invasive ability (>9000 internalized bacteria) was able to detect the presence of AIEC with high positive predictive value (80.0% [55.2–100.0]). Overall, 78.1% of the AIEC + patients were colonized by two or less different AIEC strains. The level of serum anti-total E. coli antibodies (AEcAb) was higher in AIEC-positive patients (p = 0.038) with a very high negative predictive value (96.6% [89.9–100.0]) (p = 0.038) for a cut-off value > 1.9 × 10−3.ConclusionsMore than two thirds of AIEC-positive CD patients were colonized by two or less AIEC strains. While stools samples are not accurate to screen AIEC status, the AEcAb level appears to be an attractive, rapid and easier biomarker to identify patients with Crohn's disease harboring AIEC.
Published: 2021

3. Role of mucus-bacteria interactions in Enterotoxigenic Escherichia coli (ETEC) H10407 virulence and interplay with human microbiome

Author: Thomas Sauvaitre, Josefien Van Landuyt, Claude Durif, Charlène Roussel, Adeline Sivignon, Sandrine Chalancon, Ophélie Uriot, Florence Van Herreweghen, Tom Van de Wiele, Lucie Etienne-Mesmin, Stéphanie Blanquet-Diot, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Center for Microbial Ecology and Technology (CMET), Universiteit Gent = Ghent University (UGENT), Institut sur la Nutrition et les Aliments Fonctionnels [université Laval, Québec] (INAF), Université Laval [Québec] (ULaval), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and DUTILLOY, Stéphanie
Subjects: Diarrhea, [SDV]Life Sciences [q-bio], FUNCTION, Applied Microbiology and Biotechnology, Microbiology, INTESTINAL-TRACT, GASTRIC MUCUS, COLONIZATION FACTORS, Humans, Enterotoxigenic Escherichia coli, METALLOPROTEASE, Escherichia coli Infections, Travel, SECRETED, Virulence, Bacteria, Microbiota, Interleukin-8, GUT MICROBIOTA, Mucins, Biology and Life Sciences, HEAT-LABILE ENTEROTOXIN, IN-SITU HYBRIDIZATION, BARRIER, [SDV] Life Sciences [q-bio], MODEL, Mucus, SURVIVAL, Caco-2 Cells, Biotechnology
Abstract: The intestinal mucus layer has a dual role in human health constituting a well-known microbial niche that supports gut microbiota maintenance but also acting as a physical barrier against enteric pathogens. Enterotoxigenic Escherichia coli (ETEC), the major agent responsible for traveler’s diarrhea, is able to bind and degrade intestinal mucins, representing an important but understudied virulent trait of the pathogen. Using a set of complementary in vitro approaches simulating the human digestive environment, this study aimed to describe how the mucus microenvironment could shape different aspects of the human ETEC strain H10407 pathophysiology, namely its survival, adhesion, virulence gene expression, interleukin-8 induction and interactions with human fecal microbiota. Using the TNO gastrointestinal model (TIM-1) simulating the physicochemical conditions of the human upper gastrointestinal (GI) tract, we reported that mucus secretion and physical surface sustained ETEC survival, probably by helping it to face GI stresses. When integrating the host part in Caco2/HT29-MTX co-culture model, we demonstrated that mucus secreting-cells favored ETEC adhesion and virulence gene expression, but did not impede ETEC Interleukin-8 (IL-8) induction. Furthermore, we proved that mucosal surface did not favor ETEC colonization in a complex gut microbial background simulated in batch fecal experiments. However, the mucus-specific microbiota was widely modified upon the ETEC challenge suggesting its role in the pathogen infectious cycle. Using multi-targeted in vitro approaches, this study supports the major role played by mucus in ETEC pathophysiology, opening avenues in the design of new treatment strategies.
Published: 2022

4. Gut microbes and muscle function: can probiotics make our muscles stronger?

Author: Muriel Giron, Muriel Thomas, Dominique Dardevet, Christophe Chassard, Isabelle Savary‐Auzeloux, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Unité Mixte de Recherche sur le Fromage (UMRF), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), and AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Sarcopenia, Cachexia, Probiotics, [SDV]Life Sciences [q-bio], Reproducibility of Results, Skeletal muscle, Health Promotion, Probiotic, Gastrointestinal Microbiome, Ageing, Athlete, Physiology (medical), Humans, Orthopedics and Sports Medicine, Muscle, Skeletal, Exercise, Ecosystem, ComputingMilieux_MISCELLANEOUS, Aged
Abstract: International audience; Evidence suggests that gut microbiota composition and diversity can be a determinant of skeletal muscle metabolism and functionality. This is true in catabolic (sarcopenia and cachexia) or anabolic (exercise or in athletes) situations. As gut microbiota is known to be causal in the development and worsening of metabolic dysregulation phenotypes such as obesity or insulin resistance, it can regulate, at least partially, skeletal muscle mass and function. Skeletal muscles are physiologically far from the gut. Signals generated by the gut due to its interaction with the gut microbiome (microbial metabolites, gut peptides, lipopolysaccharides, and interleukins) constitute links between gut microbiota activity and skeletal muscle and regulate muscle functionality via modulation of systemic/tissue inflammation as well as insulin sensitivity. The probiotics able to limit sarcopenia and cachexia or promote health performances in rodents are mainly lactic acid bacteria and bifidobacteria. In humans, the same bacteria have been tested, but the scarcity of the studies, the variability of the populations, and the difficulty to measure accurately and with high reproducibility muscle mass and function have not allowed to highlight specific strains able to optimize muscle mass and function. Further studies are required on more defined population, in order to design personalized nutrition. For elderly, testing the efficiency of probiotics according to the degree of frailty, nutritional state, or degree of sarcopenia before supplementation is essential. For exercise, selection of probiotics capable to be efficient in recreational and/or elite athletes, resistance, and/or endurance exercise would also require further attention. Ultimately, a combination of strategies capable to optimize muscle functionality, including bacteria (new microbes, bacterial ecosystems, or mix, more prone to colonize a specific gut ecosystem) associated with prebiotics and other 'traditional' supplements known to stimulate muscle anabolism (e.g. proteins), could be the best way to preserve muscle functionality in healthy individuals at all ages or patients.
Published: 2022

5. When idiopathic male infertility is rooted in maternal malnutrition during the perinatal period in mice

Author: Yuki Muranishi, Laurent Parry, Mélanie Vachette-Dit-Martin, Fabrice Saez, Cécile Coudy-Gandilhon, Pierre Sauvanet, David H Volle, Jérémy Tournayre, Serge Bottari, Francesca Carpentiero, Guillaume Martinez, Jana Muroňová, Jessica Escoffier, Alain Bruhat, Anne-Catherine Maurin, Julien Averous, Christophe Arnoult, Pierre Fafournoux, Céline Jousse, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Obihiro University of Agriculture and Veterinary Medicine, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Grenoble, UM de Génétique Chromosomique, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Adult, Male, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, male fertility, sperm capacitation, 03 medical and health sciences, Mice, 0302 clinical medicine, Pregnancy, Animals, Humans, Lactation, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Infertility, Male, 030304 developmental biology, 0303 health sciences, 030219 obstetrics & reproductive medicine, Malnutrition, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell Biology, General Medicine, Spermatozoa, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Fertility, Reproductive Medicine, Sperm Motility, Female, nutritional programming, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Infertility represents a growing burden worldwide, with one in seven couples presenting difficulties conceiving. Among these, 10–15% of the men have idiopathic infertility that does not correlate with any defect in the classical sperm parameters measured. In the present study, we used a mouse model to investigate the effects of maternal undernutrition on fertility in male progeny. Our results indicate that mothers fed on a low-protein diet during gestation and lactation produce male offspring with normal sperm morphology, concentration, and motility but exhibiting an overall decrease of fertility when they reach adulthood. Particularly, in contrast to control, sperm from these offspring show a remarkable lower capacity to fertilize oocytes when copulation occurs early in the estrus cycle relative to ovulation, due to an altered sperm capacitation. Our data demonstrate for the first time that maternal nutritional stress can have long-term consequences on the reproductive health of male progeny by affecting sperm physiology, especially capacitation, with no observable impact on spermatogenesis and classical quantitative and qualitative sperm parameters. Moreover, our experimental model could be of major interest to study, explain, and ultimately treat certain categories of infertilities.
Published: 2022

6. Multi-targeted properties of the probiotic saccharomyces cerevisiae CNCM I-3856 against enterotoxigenic escherichia coli (ETEC) H10407 pathogenesis across human gut models

Author: Kim De Paepe, Jana De Bodt, Sylvain Denis, Sandrine Chalancon, Pascal Vandekerkove, Tom Van de Wiele, Nathalie Ballet, Stéphanie Blanquet-Diot, Charlène Roussel, Françoise Leriche, Wessam Galia, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité Mixte de Recherche sur le Fromage (UMRF), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and Ministere de la Recherche (France) - Lesaffre Company (Marcq-en-Baroeul, France)
Subjects: IRRITABLE-BOWEL-SYNDROME, RC799-869, Enterotoxin, Gut flora, medicine.disease_cause, Probiotic, law.invention, COLONIZATION, Foodborne Diseases, law, Lactobacillus, Enterotoxigenic Escherichia coli, INFECTION, Medicine and Health Sciences, Escherichia coli Infections, Bifidobacterium, 2. Zero hunger, 0303 health sciences, FERMENTATION, biology, Gastroenterology, Diseases of the digestive system. Gastroenterology, MICROBIOTA, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Research Article, Research Paper, Microbiology (medical), foodborne pathogen, ETEC, virulence, Virulence, Saccharomyces cerevisiae, antagonism effect, Microbiology, digestive system, 03 medical and health sciences, ETHANOL, medicine, Humans, 030304 developmental biology, ASCOMYCETOUS YEASTS, gut microbiota, IDENTIFICATION, 030306 microbiology, Probiotics, Biology and Life Sciences, biology.organism_classification, PREVENTION, Gastrointestinal Microbiome, Bacterial adhesin, enterotoxin, RESISTANCE
Abstract: International audience; Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of acute traveler's diarrhea. Adhesins and enterotoxins constitute the major ETEC virulence traits. With the dramatic increase in antibiotic resistance, probiotics are considered a wholesome alternative to prevent or treat ETEC infections. Here, we examined the antimicrobial properties of the probiotic Saccharomyces cerevisiae CNCM I-3856 against ETEC H10407 pathogenesis upon co-administration in the TNO gastrointestinal Model (TIM-1), simulating the physicochemical and enzymatic conditions of the human upper digestive tract and preventive treatment in the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), integrating microbial populations of the ileum and ascending colon. Interindividual variability was assessed by separate M-SHIME experiments with microbiota from six human individuals. The probiotic did not affect ETEC survival along the digestive tract. However, ETEC pathogenicity was significantly reduced: enterotoxin encoding virulence genes were repressed, especially in the TIM-1 system, and a lower enterotoxin production was noted. M-SHIME experiments revealed that 18-days probiotic treatment stimulate the growth of Bifidobacterium and Lactobacillus in different gut regions (mucosal and luminal, ileum and ascending colon) while a stronger metabolic activity was noted in terms of short-chain fatty acids (acetate, propionate, and butyrate) and ethanol production. Moreover, the probiotic pre-treated microbiota displayed a higher robustness in composition following ETEC challenge compared to the control condition. We thus demonstrated the multi-inhibitory properties of the probiotic S. cerevisiae CNCM I-3856 against ETEC in the overall simulated human digestive tract, regardless of the inherent variability across individuals in the M-SHIME.
Published: 2021

7. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Author: Klionsky, Daniel, Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie, Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis, Adeli, Khosrow, Adolph, Timon, Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat, Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed, Agrotis, Alexander, Aguilar, Patricia, Ahmad, S Tariq, Ahmed, Zubair, Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed, Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay, Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo, Altan-Bonnet, Nihal, Altieri, Dario, Álvarez, Élida, Alves, Sara, Alves Da Costa, Cristine, Alzaharna, Mazen, Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal, Ammanathan, Veena, An, Zhenyi, Andersen, Stig, Andrabi, Shaida, Andrade-Silva, Magaiver, Andres, Allen, Angelini, Sabrina, Ann, David, Anozie, Uche, Ansari, Mohammad, Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner, Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen, Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela, Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas, Au, Alicia, Auberger, Patrick, Auner, Holger, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, Azzopardi, Maria, Baba, Misuzu, Backer, Jonathan, Backues, Steven, Bae, Dong-Hun, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric, Baek, Ahruem, Baek, Seung-Hoon, Baek, Sung Hee, Bagetta, Giacinto, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xiyuan, Bai, Yidong, Bairagi, Nandadulal, Baksi, Shounak, Balbi, Teresa, Baldari, Cosima, Balduini, Walter, Ballabio, Andrea, Ballester, Maria, Balazadeh, Salma, Balzan, Rena, Bandopadhyay, Rina, Banerjee, Sreeparna, Banerjee, Sulagna, Bánréti, Ágnes, Bao, Yan, Baptista, Mauricio, Baracca, Alessandra, Barbati, Cristiana, Bargiela, Ariadna, Barilà, Daniela, Barlow, Peter, Barmada, Sami, Barreiro, Esther, Barreto, George, Bartek, Jiri, Bartel, Bonnie, Bartolome, Alberto, Barve, Gaurav, Basagoudanavar, Suresh, Bassham, Diane, Bast, Robert, Basu, Alakananda, Batoko, Henri, Batten, Isabella, Baulieu, Etienne, Baumgarner, Bradley, Bayry, Jagadeesh, Beale, Rupert, Beau, Isabelle, Beaumatin, Florian, Bechara, Luiz, Beck, George, Beers, Michael, 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Anna, Hernández, Agustín, Hernandez, Carlos, Hernandez-Diaz, Sergio, Hernandez-Gea, Virginia, Herpin, Amaury, Herreros, Judit, Hervás, Javier, Hesselson, Daniel, Hetz, Claudio, Heussler, Volker, Higuchi, Yujiro, Hilfiker, Sabine, Hill, Joseph, Hlavacek, William, Ho, Emmanuel, Ho, Idy, Ho, Philip Wing-Lok, Ho, Shu-Leong, Ho, Wan Yun, Hobbs, G Aaron, Hochstrasser, Mark, Hoet, Peter, Hofius, Daniel, Hofman, Paul, Höhn, Annika, Holmberg, Carina, Hombrebueno, Jose, Yi-Ren Hong, Chang-Won Hong, Hooper, Lora, Hoppe, Thorsten, Horos, Rastislav, Hoshida, Yujin, Hsin, I-Lun, Hsu, Hsin-Yun, Hu, Bing, Hu, Dong, Hu, Li-Fang, Hu, Ming Chang, Hu, Ronggui, Hu, Wei, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Jinlian, Hua, Yingqi, Huan, Chongmin, Huang, Canhua, Huang, Chuanshu, Huang, Chuanxin, Huang, Chunling, Huang, Haishan, Huang, Kun, Huang, Michael, Huang, Rui, Huang, Shan, Huang, Tianzhi, Huang, Xing, Huang, Yuxiang Jack, Huber, Tobias, Hubert, Virginie, Hubner, Christian, Hughes, Stephanie, 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Da-Hye, Lee, Edward, Lee, Erinna, Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu, Lee, Jae Man, Lee, Jason, Lee, Jin-A, Lee, Joo-Yong, Lee, Jun Hee, Lee, Michael, Lee, Min Goo, Lee, Min Jae, Lee, Myung-Shik, Lee, Sang Yoon, Lee, Seung-Jae, Lee, Stella, Lee, Sung Bae, Lee, Won Hee, Lee, Ying-Ray, Lee, Yong-ho, Lee, Youngil, Lefebvre, Christophe, Legouis, Renaud, Lei, Yu, Lei, Yuchen, Leikin, Sergey, Leitinger, Gerd, Lemus, Leticia, Leng, Shuilong, Lenoir, Olivia, Lenz, Guido, Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda, Leopoldino, Andréia, Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth, Leung, Chi-Ting, Leung, Po Sing, Leventhal, Jeremy, Levine, Beth, Lewis, Patrick, Ley, Klaus, Li, Bin, Li, Da-Qiang, Li, Jianming, Li, Jing, Li, Jiong, Li, Ke, Li, Liwu, Li, Mei, Li, Min, Li, Ming, Li, Mingchuan, Li, Pin-Lan, Li, Ming-Qing, Li, Qing, Li, Sheng, Li, Tiangang, Li, Wei, Li, Wenming, Li, Xue, Li, Yi-Ping, Li, Yuan, Li, Zhiqiang, Li, Zhiyong, Li, Zhiyuan, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl, Lilly, Mary, Lim, Hyunjung, Lima, Thania, Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie, Lin, Kurt, Lin, Kwang-Huei, Lin, Liang-Tzung, LIN, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia, Liou, Yih-Cherng, Lipinski, Marta, Lipovšek, Saška, Lira, Vitor, Lisiak, Natalia, Liton, Paloma, Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, 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Mengxiao, Ma, Ning-Fang, Ma, Quan-Hong, Ma, Xinliang, Ma, Yueyun, Ma, Zhenyi, MacDougald, Ormond, Macian, Fernando, MacIntosh, Gustavo, MacKeigan, Jeffrey, Macleod, Kay, Maday, Sandra, Madeo, Frank, Madesh, Muniswamy, Madl, Tobias, Madrigal-Matute, Julio, Maeda, Akiko, Maejima, Yasuhiro, Magarinos, Marta, Mahavadi, Poornima, Maiani, Emiliano, Maiese, Kenneth, Maiti, Panchanan, Maiuri, Maria Chiara, Majello, Barbara, Major, Michael, Makareeva, Elena, Malik, Fayaz, Mallilankaraman, Karthik, Malorni, Walter, Maloyan, Alina, Mammadova, Najiba, Man, Gene Chi Wai, Manai, Federico, Mancias, Joseph, Mandelkow, Eva-Maria, Mandell, Michael, Manfredi, Angelo, Manjili, Masoud, Manjithaya, Ravi, Manque, Patricio, Manshian, Bella, Manzano, Raquel, Manzoni, Claudia, Mao, Kai, Marchese, Cinzia, Marchetti, Sandrine, Marconi, Anna Maria, Marcucci, Fabrizio, Mardente, Stefania, Mareninova, Olga, Margeta, Marta, Mari, Muriel, Marinelli, Sara, Marinelli, Oliviero, Mariño, Guillermo, Mariotto, Sofia, Marshall, Richard, Marten, Mark, Martens, Sascha, Martin, Alexandre, Martin, Katie, Martin, Sara, Martin, Shaun, Martín-Segura, Adrián, Martín-Acebes, Miguel, Martin-Burriel, Inmaculada, Martin-Rincon, Marcos, Martin-Sanz, Paloma, Martina, José, Martinet, Wim, Martinez, Aitor, Martinez, Ana, Martinez, Jennifer, Martinez Velazquez, Moises, Martinez-Lopez, Nuria, Martinez-Vicente, Marta, Martins, Daniel, Martins, Joilson, Martins, Waleska, Martins-Marques, Tania, Marzetti, Emanuele, Masaldan, Shashank, Masclaux-Daubresse, Celine, Mashek, Douglas, Massa, Valentina, Massieu, Lourdes, Masson, Glenn, Masuelli, Laura, Masyuk, Anatoliy, Masyuk, Tetyana, Matarrese, Paola, Matheu, Ander, Matoba, Satoaki, Matsuzaki, Sachiko, Mattar, Pamela, Matte, Alessandro, Mattoscio, Domenico, Mauriz, José, Mauthe, Mario, Mauvezin, Caroline, Maverakis, Emanual, Maycotte, Paola, Mayer, Johanna, Mazzoccoli, Gianluigi, Mazzoni, Cristina, Mazzulli, Joseph, McCarty, Nami, Mcdonald, Christine, McGill, Mitchell, 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Sahni, Sumit, Saito, Nayuta, Saito, Shigeru, Saito, Tsunenori, Sakai, Ryohei, Sakai, Yasuyoshi, Sakamaki, Jun-Ichi, Saksela, Kalle, Salazar, Gloria, Salazar-Degracia, Anna, Salekdeh, Ghasem, Saluja, Ashok, Sampaio-Marques, Belém, Sanchez, Maria Cecilia, Sanchez-Alcazar, Jose, Sanchez-Vera, Victoria, Sancho-Shimizu, Vanessa, Sanderson, J Thomas, Sandri, Marco, Santaguida, Stefano, Santambrogio, Laura, Santana, Magda, Santoni, Giorgio, Sanz, Alberto, Sanz, Pascual, Saran, Shweta, Sardiello, Marco, Sargeant, Timothy, Sarin, Apurva, Sarkar, Chinmoy, Sarkar, Sovan, Sarrias, Maria-Rosa, Sarkar, Surajit, Sarmah, Dipanka Tanu, Sarparanta, Jaakko, Sathyanarayan, Aishwarya, Sathyanarayanan, Ranganayaki, Scaglione, K Matthew, Scatozza, Francesca, Schaefer, Liliana, Schafer, Zachary, Schaible, Ulrich, Schapira, Anthony, Scharl, Michael, Schatzl, Hermann, Schein, Catherine, Scheper, Wiep, Scheuring, David, Schiaffino, Maria Vittoria, Schiappacassi, Monica, Schindl, Rainer, Schlattner, Uwe, Schmidt, Oliver, Schmitt, Roland, Schmidt, Stephen, Schmitz, Ingo, Schmukler, Eran, Schneider, Anja, Schneider, Bianca, Schober, Romana, Schoijet, Alejandra, Schott, Micah, Schramm, Michael, Schröder, Bernd, Schuh, Kai, Schüller, Christoph, Schulze, Ryan, Schürmanns, Lea, Schwamborn, Jens, Schwarten, Melanie, Scialo, Filippo, Sciarretta, Sebastiano, Scott, Melanie, Scotto, Kathleen, Scovassi, A Ivana, Scrima, Andrea, Scrivo, Aurora, Sebastian, David, Sebti, Salwa, Sedej, Simon, Segatori, Laura, Segev, Nava, Seglen, Per, Seiliez, Iban, Seki, Ekihiro, Selleck, Scott, Sellke, Frank, Selsby, Joshua, Sendtner, Michael, Senturk, Serif, Seranova, Elena, Sergi, Consolato, Serra-Moreno, Ruth, Sesaki, Hiromi, Settembre, Carmine, Setty, Subba Rao Gangi, Sgarbi, Gianluca, Sha, Ou, Shacka, John, Shah, Javeed, Shang, Dantong, Shao, Changshun, Shao, Feng, Sharbati, Soroush, Sharkey, Lisa, Sharma, Dipali, Sharma, Gaurav, Sharma, Kulbhushan, Sharma, Pawan, Sharma, Surendra, Shen, Han-Ming, Shen, Hongtao, Shen, Jiangang, Shen, Ming, Shen, Weili, Shen, Zheni, Sheng, Rui, Sheng, Zhi, Sheng, Zu-Hang, Shi, Jianjian, Shi, Xiaobing, Shi, Ying-Hong, Shiba-Fukushima, Kahori, Shieh, Jeng-Jer, Shimada, Yohta, Shimizu, Shigeomi, Shimozawa, Makoto, Shintani, Takahiro, Shoemaker, Christopher, Shojaei, Shahla, Shoji, Ikuo, Shravage, Bhupendra, Shridhar, Viji, Shu, Chih-Wen, Shu, Hong-Bing, Shui, Ke, Shukla, Arvind, Shutt, Timothy, Sica, Valentina, Siddiqui, Aleem, Sierra, Amanda, Sierra-Torre, Virginia, Signorelli, Santiago, Sil, Payel, Silva, Bruno, Silva, Johnatas, Silva-Pavez, Eduardo, Silvente-Poirot, Sandrine, Simmonds, Rachel, Simon, Anna Katharina, Simon, Hans-Uwe, Simons, Matias, Singh, Anurag, Singh, Lalit, Singh, Rajat, Singh, Shivendra, Singh, Shrawan, Singh, Sudha, Singh, Sunaina, Singh, Surinder Pal, Sinha, Debasish, Sinha, Rohit Anthony, Sinha, Sangita, Sirko, Agnieszka, Sirohi, Kapil, Sivridis, Efthimios, Skendros, Panagiotis, Skirycz, Aleksandra, Slaninová, Iva, Smaili, Soraya, Smertenko, Andrei, Smith, Matthew, Soenen, Stefaan, Sohn, Eun Jung, Sok, Sophia, Solaini, Giancarlo, Soldati, Thierry, Soleimanpour, Scott, Soler, Rosa, Solovchenko, Alexei, Somarelli, Jason, Sonawane, Avinash, Song, Fuyong, Song, Hyun Kyu, Song, Ju-Xian, Song, Kunhua, Song, Zhiyin, Soria, Leandro, Sorice, Maurizio, Soukas, Alexander, Soukup, Sandra-Fausia, Sousa, Diana, Sousa, Nadia, Spagnuolo, Paul, Spector, Stephen, Srinivas Bharath, M., St Clair, Daret, Stagni, Venturina, Staiano, Leopoldo, Stalnecker, Clint, Stankov, Metodi, Stathopulos, Peter, Stefan, Katja, Stefan, Sven Marcel, Stefanis, Leonidas, Steffan, Joan, Steinkasserer, Alexander, Stenmark, Harald, Sterneckert, Jared, Stevens, Craig, Stoka, Veronika, Storch, Stephan, Stork, Björn, Strappazzon, Flavie, Strohecker, Anne Marie, Stupack, Dwayne, Su, Huanxing, Su, Ling-Yan, Su, Longxiang, Suarez-Fontes, Ana, Subauste, Carlos, Subbian, Selvakumar, Subirada, Paula, Sudhandiran, Ganapasam, Sue, Carolyn, Sui, Xinbing, Summers, Corey, Sun, Guangchao, Sun, Jun, SUN, Kang, Sun, Meng-xiang, Sun, Qiming, Sun, Yi, Sun, Zhongjie, Sunahara, Karen, Sundberg, Eva, Susztak, Katalin, Sutovsky, Peter, Suzuki, Hidekazu, Sweeney, Gary, Symons, J David, Sze, Stephen Cho Wing, Szewczyk, Nathaniel, Tabęcka-Łonczynska, Anna, Tabolacci, Claudio, Tacke, Frank, Taegtmeyer, Heinrich, Tafani, Marco, Tagaya, Mitsuo, Tai, Haoran, Tait, Stephen, Takahashi, Yoshinori, Takats, Szabolcs, Talwar, Priti, Tam, Chit, Tam, Shing Yau, Tampellini, Davide, Tamura, Atsushi, Tan, Chong Teik, Tan, Eng-King, Tan, Ya-Qin, Tanaka, Masaki, Tanaka, Motomasa, Tang, Daolin, Tang, Jingfeng, Tang, Tie-Shan, Tanida, Isei, Tao, Zhipeng, Taouis, Mohammed, Tatenhorst, Lars, Tavernarakis, Nektarios, Taylor, Allen, Taylor, Gregory, Taylor, Joan, Tchetina, Elena, Tee, Andrew, Tegeder, Irmgard, Teis, David, Teixeira, Natercia, Teixeira-Clerc, Fatima, Tekirdag, Kumsal, Tencomnao, Tewin, Tenreiro, Sandra, Tepikin, Alexei, Testillano, Pilar, Tettamanti, Gianluca, Tharaux, Pierre-Louis, Thedieck, Kathrin, Thekkinghat, Arvind, Thellung, Stefano, Thinwa, Josephine, Thirumalaikumar, V.P., Thomas, Sufi Mary, Thomes, Paul, Thorburn, Andrew, Thukral, Lipi, Thum, Thomas, Thumm, Michael, Tian, Ling, Tichy, Ales, Till, Andreas, Timmerman, Vincent, Titorenko, Vladimir, Todi, Sokol, Todorova, Krassimira, Toivonen, Janne, Tomaipitinca, Luana, Tomar, Dhanendra, Tomas-Zapico, Cristina, Tomić, Sergej, Tong, Benjamin Chun-Kit, Tong, Chao, Tong, Xin, Tooze, Sharon, Torgersen, Maria, Torii, Satoru, Torres-López, Liliana, Torriglia, Alicia, Towers, Christina, Towns, Roberto, Toyokuni, Shinya, Trajkovic, Vladimir, Tramontano, Donatella, Tran, Quynh-Giao, Travassos, Leonardo, Trelford, Charles, Tremel, Shirley, Trougakos, Ioannis, Tsao, Betty, Tschan, Mario, Tse, Hung-Fat, Tse, Tak Fu, Tsugawa, Hitoshi, Tsvetkov, Andrey, Tumbarello, David, Tumtas, Yasin, Tuñón, María, Turcotte, Sandra, Turk, Boris, Turk, Vito, Turner, Bradley, Tuxworth, Richard, Tyler, Jessica, Tyutereva, Elena, Uchiyama, Yasuo, Ugun-Klusek, Aslihan, Uhlig, Holm, Ułamek-Kozioł, Marzena, Ulasov, Ilya, Umekawa, Midori, Ungermann, Christian, Unno, Rei, Urbe, Sylvie, Uribe-Carretero, Elisabet, Üstün, Suayib, Uversky, Vladimir, Vaccari, Thomas, Vaccaro, Maria, Vahsen, Björn, Vakifahmetoglu-Norberg, Helin, Valdor, Rut, Valente, Maria, Valko, Ayelén, Vallee, Richard, Valverde, Angela, Van Den Berghe, Greet, van der Veen, Stijn, Van Kaer, Luc, van Loosdregt, Jorg, van Wijk, Sjoerd, Vandenberghe, Wim, Vanhorebeek, Ilse, Vannier-Santos, Marcos, Vannini, Nicola, Vanrell, M Cristina, Vantaggiato, Chiara, Varano, Gabriele, Varela-Nieto, Isabel, Varga, Máté, Vasconcelos, M Helena, Vats, Somya, Vavvas, Demetrios, Vega-Naredo, Ignacio, Vega-Rubin-de-Celis, Silvia, Velasco, Guillermo, Velázquez, Ariadna, Vellai, Tibor, Vellenga, Edo, Velotti, Francesca, Verdier, Mireille, Verginis, Panayotis, Vergne, Isabelle, Verkade, Paul, Verma, Manish, Verstreken, Patrik, Vervliet, Tim, Vervoorts, Jörg, Vessoni, Alexandre, Victor, Victor, Vidal, Michel, Vidoni, Chiara, Vieira, Otilia, Vierstra, Richard, Viganó, Sonia, Vihinen, Helena, Vijayan, Vinoy, Vila, Miquel, Vilar, Marçal, Villalba, José, Villalobo, Antonio, Villarejo-Zori, Beatriz, Villarroya, Francesc, Villarroya, Joan, Vincent, Olivier, Vindis, Cecile, Viret, Christophe, Viscomi, Maria Teresa, Visnjic, Dora, Vitale, Ilio, Vocadlo, David, Voitsekhovskaja, Olga, Volonté, Cinzia, Volta, Mattia, Vomero, Marta, Von Haefen, Clarissa, Vooijs, Marc, Voos, Wolfgang, Vucicevic, Ljubica, Wade-Martins, Richard, Waguri, Satoshi, Waite, Kenrick, Wakatsuki, Shuji, Walker, David, Walker, Mark, Walker, Simon, Walter, Jochen, Wandosell, Francisco, Wang, Bo, Wang, Chao-Yung, Wang, Chen, Wang, Chenran, Wang, Chenwei, Wang, Cun-Yu, Wang, Dong, Wang, Fangyang, Wang, Feng, Wang, Fengming, Wang, Guansong, Wang, Han, Wang, Hao, Wang, Hexiang, Wang, Hong-Gang, Wang, Jianrong, Wang, Jigang, Wang, Jiou, Wang, Jundong, Wang, Kui, Wang, Lianrong, Wang, Liming, Wang, Maggie Haitian, Wang, Meiqing, Wang, Nanbu, Wang, PengWei, Wang, PeiPei, Wang, Ping, Wang, Qing Jun, Wang, Qing, Wang, Qing Kenneth, Wang, Qiong, Wang, Wen-Tao, Wang, Wuyang, Wang, Xinnan, Wang, Xuejun, Wang, Yan, Wang, Yanchang, Wang, Yanzhuang, Wang, Yen-Yun, Wang, Yihua, Wang, Yipeng, Wang, Yu, wang, yuqi, Wang, Zhe, Wang, Zhenyu, Wang, Zhouguang, Warnes, Gary, Warnsmann, Verena, Watada, Hirotaka, Watanabe, Eizo, Watchon, Maxinne, Wawrzyńska, Anna, Weaver, Timothy, Wegrzyn, Grzegorz, Wehman, Ann, Wei, Huafeng, Wei, Lei, Wei, Taotao, Wei, Yongjie, Weiergräber, Oliver, Weihl, Conrad, Weindl, Günther, Weiskirchen, Ralf, Wells, Alan, Wen, Runxia, Wen, Xin, Werner, Antonia, Weykopf, Beatrice, Wheatley, Sally, Whitton, J Lindsay, Whitworth, Alexander, Wiktorska, Katarzyna, Wildenberg, Manon, Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin, Williams, Roger, Williamson, Peter, Wilson, Richard, Winner, Beate, Winsor, Nathaniel, Witkin, Steven, Wodrich, Harald, Woehlbier, Ute, Wollert, Thomas, Wong, Esther, Wong, Jack Ho, Wong, Richard, Wong, Vincent Kam Wai, Wong, W Wei-Lynn, Wu, An-Guo, Wu, Chengbiao, Wu, Jian, Wu, Junfang, Wu, Kenneth, Wu, Min, Wu, Shan-Ying, Wu, Shengzhou, Wu, Shu-Yan, Wu, Shufang, Wu, William, Wu, Xiaohong, Wu, Xiaoqing, Wu, Yao-Wen, Wu, Yihua, Xavier, Ramnik, Xia, Hongguang, Xia, Lixin, Xia, Zhengyuan, Xiang, Ge, Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xiao, Guozhi, Xiao, Hengyi, Xiao, Hong-tao, Xiao, Jian, Xiao, Lan, Xiao, Shi, Xiao, Yin, Xie, Baoming, Xie, Chuan-Ming, Xie, Min, Xie, Yuxiang, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xu, Congfeng, Xu, En, Xu, Haoxing, Xu, Jing, Xu, Jinrong, Xu, Liang, Xu, Wen Wen, Xu, Xiulong, Xue, Yu, Yakhine-Diop, Sokhna, Yamaguchi, Masamitsu, Yamaguchi, Osamu, Yamamoto, Ai, Yamashina, Shunhei, Yan, Shengmin, Yan, Shian-Jang, Yan, Zhen, Yanagi, Yasuo, Yang, Chuanbin, Yang, Dun-Sheng, Yang, Huan, Yang, Huang-Tian, Yang, Hui, Yang, Jin-Ming, Yang, Jing, Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin, Yiu, Stephanie Pei Tung, Yoo, Young, Yoshida, Kiyotsugu, Yoshii, Saori, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond, Zacks, David, Zaffagnini, Gabriele, Zambelli, Vanessa, Zanella, Isabella, Zang, Qun, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott, Zeng, Jialiu, Zeng, Ju-deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin, Zhang, Leshuai, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Boris, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, ZHOU, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith, Stallings, Christina, Tong, Chun-Kit, Ahmad, S. Tariq, Alim Al-Bari, M. Abdul, Bechara, Luiz R.G., Behrens, Georg M.N., Bhuiyan, Md. Shenuarin, Broaddus, V. Courtney, Buchan, J. Ross, Burón, M. Isabel, Carter, A. Brent, Chan, Matthew T.V., Choi, Augustine M.K., D’Adamo, Stefania, D’Amelio, Marcello, D’Arcangelo, Daniela, D’Lugos, Andrew, D’Orazi, Gabriella, De Meyer, Guido R.Y., Delpino, M. Victoria, Distler, Jörg H.W., Dixon, Ian M.C., Dobson, Renwick C.J., 2nd Dorn, Gerald, Eissa, N. Tony, Engelsen, Agnete S.T., Fairlie, W. Douglas, Ferreira, Julio C.B., H.B., Ranjitha, Hanson, Phyllis I., Hejtmancik, J. Fielding, Ho, Idy H.T., Hobbs, G. Aaron, Hoet, Peter H.M., Huang, Michael L.H., Iyer, Anand Krishnan V., Johnson, Gail V.W., Joosten, Leo A.B., Karim, Md. Razaul, Kaufmann, Stefan H.E., Ko, Ben C.B., Leck, Lionel Y.W., Lima, Thania R.R., Livingston, J. Andrew, Martin, Alexandre P.J., Montes, L. Ruth, Murphy, J. Patrick, Ng, Charlene C.W., Nicolao, M. Celeste, O’Donovan, Tracey, O’Leary, Seónadh, O’Rourke, Eyleen, O’Sullivan, Mary, O’Sullivan, Timothy, Omary, M. Bishr, Pereira, Gustavo J.S., Ratnayaka, J. Arjuna, Riazuddin, S. Amer, Rouschop, Kasper M.A., Sanderson, J. Thomas, Scaglione, K. Matthew, Schapira, Anthony H.V., Scovassi, A. Ivana, St. Clair, Daret, Sunahara, Karen K.S., Symons, J. David, Triola, Gemma, van Wijk, Sjoerd J.L., Vanrell, M. Cristina, Vasconcelos, M. Helena, Whitton, J. Lindsay, Williams, Robin S.B., Wong, W. Wei-Lynn, Wu, William K.K., Yakhine-Diop, Sokhna M.S., Yu, W. Haung, Zhang, Kalin Y.B., Dong, X. Charlie, Ain Shams University [ASU], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University [JGU], Medical University Graz, Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Institut Pasteur d'Iran, Leibniz Institute of Plant Biochemistry [IPB], The University of Texas M.D. Anderson Cancer Center [Houston], Institut de pharmacologie moléculaire et cellulaire [IPMC], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre méditerranéen de médecine moléculaire [C3M], Institut de Biologie Valrose [IBV], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Institut NeuroMyoGène [INMG], Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Marqueurs cardiovasculaires en situation de stress [MASCOT (UMR_S_942 / U942)], Institut de Recherche sur le Cancer et le Vieillissement [IRCAN], Centre de Recherche en Cancérologie de Marseille [CRCM], Centre for Integrative Biology - CBI [Inserm U964 - CNRS UMR7104 - IGBMC], Oncogenesis, Stress, Signaling [OSS], Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)], Institut de Biologie Intégrative de la Cellule [I2BC], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH], Centre de Recherches en Cancérologie de Toulouse [CRCT], Physiopathologie et traitement des maladies du foie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC], Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] [BIO-PEROXIL], Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], Unité de génétique et biologie des cancers [U830], Laboratoire d'Optique et Biosciences [LOB], Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC], Différenciation et communication neuronale et neuroendocrine [DC2N], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Centre d'Immunologie de Marseille - Luminy [CIML], Physiopathologie et imagerie des troubles neurologiques [PhIND], Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [LBFA], Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163], Institut Mondor de Recherche Biomédicale [IMRB], Franco-czech Laboratory for clinical research on obesity, University of Michigan [Ann Arbor], University of Michigan System, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 de Paris (UP), Institut NeuroMyoGène (INMG), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institute of genetics and molecular and cellular biology-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), 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), 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), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epithelial biology and disease - Liliane Bettencourt Chair of Developmental Biology (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), 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), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the National Institute of General Medical Sciences [GM131919]., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Department of Women's and Children's Health [Stockholm, Sweden], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA)-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)-École polytechnique (X), 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, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), 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), Life Sciences Institute [Ann Arbor, MI, USA], University of Michigan System-University of Michigan System, European Institute of Oncology IRCCS [Milan, Italy] (EIO), Ain Shams University (ASU), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Leibniz Institute of Plant Biochemistry (IPB), Hebrew University of Jerusalem, 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)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, 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), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., Agrewala, J. N., Agrotis, A., Aguilar, P. V., Ahmad, S. T., Ahmed, Z. M., Ahumada-Castro, U., Aits, S., Aizawa, S., Akkoc, Y., Akoumianaki, T., Akpinar, H. A., Al-Abd, A. M., Al-Akra, L., Al-Gharaibeh, A., Alaoui-Jamali, M. A., Alberti, S., Alcocer-Gomez, E., Alessandri, C., Ali, M., Alim Al-Bari, M. A., Aliwaini, S., Alizadeh, J., Almacellas, E., Almasan, A., Alonso, A., Alonso, G. D., Altan-Bonnet, N., Altieri, D. C., Alvarez, E. M. C., Alves, S., Alves da Costa, C., Alzaharna, M. M., Amadio, M., Amantini, C., Amaral, C., Ambrosio, S., Amer, A. O., Ammanathan, V., An, Z., Andersen, S. U., Andrabi, S. A., Andrade-Silva, M., Andres, A. M., Angelini, S., Ann, D., Anozie, U. C., Ansari, M. Y., Antas, P., Antebi, A., Anton, Z., Anwar, T., Apetoh, L., Apostolova, N., Araki, T., Araki, Y., Arasaki, K., Araujo, W. L., Araya, J., Arden, C., Arevalo, M. -A., Arguelles, S., Arias, E., Arikkath, J., Arimoto, H., Ariosa, A. R., Armstrong-James, D., Arnaune-Pelloquin, L., Aroca, A., Arroyo, D. S., Arsov, I., Artero, R., Asaro, D. M. L., Aschner, M., Ashrafizadeh, M., Ashur-Fabian, O., Atanasov, A. G., Au, A. K., Auberger, P., Auner, H. W., Aurelian, L., Autelli, R., Avagliano, L., Avalos, Y., Aveic, S., Aveleira, C. A., Avin-Wittenberg, T., Aydin, Y., Ayton, S., Ayyadevara, S., Azzopardi, M., Baba, M., Backer, J. M., Backues, S. K., Bae, D. -H., Bae, O. -N., Bae, S. H., Baehrecke, E. H., Baek, A., Baek, S. -H., Baek, S. H., Bagetta, G., Bagniewska-Zadworna, A., Bai, H., Bai, J., Bai, X., Bai, Y., Bairagi, N., Baksi, S., Balbi, T., Baldari, C. T., Balduini, W., Ballabio, A., Ballester, M., Balazadeh, S., Balzan, R., Bandopadhyay, R., Banerjee, S., Banreti, A., Bao, Y., Baptista, M. S., Baracca, A., Barbati, C., Bargiela, A., Barila, D., Barlow, P. G., Barmada, S. J., Barreiro, E., Barreto, G. E., Bartek, J., Bartel, B., Bartolome, A., Barve, G. R., Basagoudanavar, S. H., Bassham, D. C., Bast, R. C., Basu, A., Batoko, H., Batten, I., Baulieu, E. E., Baumgarner, B. L., Bayry, J., Beale, R., Beau, I., Beaumatin, F., Bechara, L. R. G., Beck, G. R., Beers, M. F., Begun, J., Behrends, C., Behrens, G. M. N., Bei, R., Bejarano, E., Bel, S., Behl, C., Belaid, A., Belgareh-Touze, N., Bellarosa, C., Belleudi, F., Bello Perez, M., Bello-Morales, R., Beltran, J. S. D. O., Beltran, S., Benbrook, D. M., Bendorius, M., Benitez, B. A., Benito-Cuesta, I., Bensalem, J., Berchtold, M. W., Berezowska, S., Bergamaschi, D., Bergami, M., Bergmann, A., Berliocchi, L., Berlioz-Torrent, C., Bernard, A., Berthoux, L., Besirli, C. G., Besteiro, S., Betin, V. M., Beyaert, R., Bezbradica, J. S., Bhaskar, K., Bhatia-Kissova, I., Bhattacharya, R., Bhattacharya, S., Bhattacharyya, S., Bhuiyan, M. S., Bhutia, S. K., Bi, L., Bi, X., Biden, T. J., Bijian, K., Billes, V. A., Binart, N., Bincoletto, C., Birgisdottir, A. B., Bjorkoy, G., Blanco, G., Blas-Garcia, A., Blasiak, J., Blomgran, R., Blomgren, K., Blum, J. S., Boada-Romero, E., Boban, M., Boesze-Battaglia, K., Boeuf, P., Boland, B., Bomont, P., Bonaldo, P., Bonam, S. R., Bonfili, L., Bonifacino, J. S., Boone, B. A., Bootman, M. D., Bordi, M., Borner, C., Bornhauser, B. C., Borthakur, G., Bosch, J., Bose, S., Botana, L. M., Botas, J., Boulanger, C. M., Boulton, M. E., Bourdenx, M., Bourgeois, B., Bourke, N. M., Bousquet, G., Boya, P., Bozhkov, P. V., Bozi, L. H. M., Bozkurt, T. O., Brackney, D. E., Brandts, C. H., Braun, R. J., Braus, G. H., Bravo-Sagua, R., Bravo-San Pedro, J. M., Brest, P., Bringer, M. -A., Briones-Herrera, A., Broaddus, V. C., Brodersen, P., Brodsky, J. L., Brody, S. L., Bronson, P. G., Bronstein, J. M., Brown, C. N., Brown, R. E., Brum, P. C., Brumell, J. H., Brunetti-Pierri, N., Bruno, D., Bryson-Richardson, R. J., Bucci, C., Buchrieser, C., Bueno, M., Buitrago-Molina, L. E., Buraschi, S., Buch, S., Buchan, J. R., Buckingham, E. M., Budak, H., Budini, M., Bultynck, G., Burada, F., Burgoyne, J. R., Buron, M. I., Bustos, V., Buttner, S., Butturini, E., Byrd, A., Cabas, I., Cabrera-Benitez, S., Cadwell, K., Cai, J., Cai, L., Cai, Q., Cairo, M., Calbet, J. A., Caldwell, G. A., Caldwell, K. A., Call, J. A., Calvani, R., Calvo, A. C., Calvo-Rubio Barrera, M., Camara, N. O. S., Camonis, J. H., Camougrand, N., Campanella, M., Campbell, E. M., Campbell-Valois, F. -X., Campello, S., Campesi, I., Campos, J. C., Camuzard, O., Cancino, J., Candido de Almeida, D., Canesi, L., Caniggia, I., Canonico, B., Canti, C., Cao, B., Caraglia, M., Carames, B., Carchman, E. 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K., Chang, C. -P., Chang, C., Chang, H. -C., Chang, K., Chao, J., Chapman, T., Charlet-Berguerand, N., Chatterjee, S., Chaube, S. K., Chaudhary, A., Chauhan, S., Chaum, E., Checler, F., Cheetham, M. E., Chen, C. -S., Chen, G. -C., Chen, J. -F., Chen, L. L., Chen, L., Chen, M., Chen, M. -K., Chen, N., Chen, Q., Chen, R. -H., Chen, S., Chen, W., Chen, X. -M., Chen, X. -W., Chen, X., Chen, Y., Chen, Y. -G., Chen, Y. -J., Chen, Y. -Q., Chen, Z. S., Chen, Z., Chen, Z. -H., Chen, Z. J., Cheng, H., Cheng, J., Cheng, S. -Y., Cheng, W., Cheng, X., Cheng, X. -T., Cheng, Y., Cheng, Z., Cheong, H., Cheong, J. K., Chernyak, B. V., Cherry, S., Cheung, C. F. R., Cheung, C. H. A., Cheung, K. -H., Chevet, E., Chi, R. J., Chiang, A. K. S., Chiaradonna, F., Chiarelli, R., Chiariello, M., Chica, N., Chiocca, S., Chiong, M., Chiou, S. -H., Chiramel, A. I., Chiurchiu, V., Cho, D. -H., Choe, S. -K., Choi, A. M. K., Choi, M. E., Choudhury, K. R., Chow, N. S., Chu, C. T., Chua, J. P., Chua, J. J. 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M., Villalobo, A., Villarejo-Zori, B., Villarroya, F., Villarroya, J., Vincent, O., Vindis, C., Viret, C., Viscomi, M. T., Visnjic, D., Vitale, I., Vocadlo, D. J., Voitsekhovskaja, O. V., Volonte, C., Volta, M., Vomero, M., Von Haefen, C., Vooijs, M. A., Voos, W., Vucicevic, L., Wade-Martins, R., Waguri, S., Waite, K. A., Wakatsuki, S., Walker, D. W., Walker, M. J., Walker, S. A., Walter, J., Wandosell, F. G., Wang, B., Wang, C. -Y., Wang, C., Wang, D., Wang, F., Wang, G., Wang, H., Wang, H. -G., Wang, J., Wang, K., Wang, L., Wang, M. H., Wang, M., Wang, N., Wang, P., Wang, Q. J., Wang, Q., Wang, Q. K., Wang, Q. A., Wang, W. -T., Wang, W., Wang, X., Wang, Y., Wang, Y. -Y., Wang, Z., Warnes, G., Warnsmann, V., Watada, H., Watanabe, E., Watchon, M., Wawrzynska, A., Weaver, T. E., Wegrzyn, G., Wehman, A. M., Wei, H., Wei, L., Wei, T., Wei, Y., Weiergraber, O. H., Weihl, C. C., Weindl, G., Weiskirchen, R., Wells, A., Wen, R. H., Wen, X., Werner, A., Weykopf, B., Wheatley, S. P., Whitton, J. L., Whitworth, A. J., Wiktorska, K., Wildenberg, M. E., Wileman, T., Wilkinson, S., Willbold, D., Williams, B., Williams, R. S. B., Williams, R. L., Williamson, P. R., Wilson, R. A., Winner, B., Winsor, N. J., Witkin, S. S., Wodrich, H., Woehlbier, U., Wollert, T., Wong, E., Wong, J. H., Wong, R. W., Wong, V. K. W., Wong, W. W. -L., Wu, A. -G., Wu, C., Wu, J., Wu, K. K., Wu, M., Wu, S. -Y., Wu, S., Wu, W. K. K., Wu, X., Wu, Y. -W., Wu, Y., Xavier, R. J., Xia, H., Xia, L., Xia, Z., Xiang, G., Xiang, J., Xiang, M., Xiang, W., Xiao, B., Xiao, G., Xiao, H., Xiao, H. -T., Xiao, J., Xiao, L., Xiao, S., Xiao, Y., Xie, B., Xie, C. -M., Xie, M., Xie, Y., Xie, Z., Xilouri, M., Xu, C., Xu, E., Xu, H., Xu, J., Xu, L., Xu, W. W., Xu, X., Xue, Y., Yakhine-Diop, S. M. S., Yamaguchi, M., Yamaguchi, O., Yamamoto, A., Yamashina, S., Yan, S., Yan, S. -J., Yan, Z., Yanagi, Y., Yang, C., Yang, D. -S., Yang, H., Yang, H. -T., Yang, J. -M., Yang, J., Yang, L., Yang, M., Yang, P. -M., Yang, Q., Yang, S., Yang, S. -F., Yang, W., Yang, W. Y., Yang, X., Yang, Y., Yao, H., Yao, S., Yao, X., Yao, Y. -G., Yao, Y. -M., Yasui, T., Yazdankhah, M., Yen, P. M., Yi, C., Yin, X. -M., Yin, Y., Yin, Z., Ying, M., Ying, Z., Yip, C. K., Yiu, S. P. T., Yoo, Y. H., Yoshida, K., Yoshii, S. R., Yoshimori, T., Yousefi, B., Yu, B., Yu, H., Yu, J., Yu, L., Yu, M. -L., Yu, S. -W., Yu, V. C., Yu, W. H., Yu, Z., Yuan, J., Yuan, L. -Q., Yuan, S., Yuan, S. -S. F., Yuan, Y., Yuan, Z., Yue, J., Yue, Z., Yun, J., Yung, R. L., Zacks, D. N., Zaffagnini, G., Zambelli, V. O., Zanella, I., Zang, Q. S., Zanivan, S., Zappavigna, S., Zaragoza, P., Zarbalis, K. S., Zarebkohan, A., Zarrouk, A., Zeitlin, S. O., Zeng, J., Zeng, J. -D., Zerovnik, E., Zhan, L., Zhang, B., Zhang, D. D., Zhang, H., Zhang, H. -L., Zhang, J., Zhang, J. -P., Zhang, K. Y. B., Zhang, L. W., Zhang, L., Zhang, M., Zhang, P., Zhang, S., Zhang, W., Zhang, X., Zhang, X. -W., Zhang, X. D., Zhang, Y., Zhang, Y. -D., Zhang, Y. -Y., Zhang, Z., Zhao, H., Zhao, L., Zhao, S., Zhao, T., Zhao, X. -F., Zhao, Y., Zheng, G., Zheng, K., Zheng, L., Zheng, S., Zheng, X. -L., Zheng, Y., Zheng, Z. -G., Zhivotovsky, B., Zhong, Q., Zhou, A., Zhou, B., Zhou, C., Zhou, G., Zhou, H., Zhou, J., Zhou, K., Zhou, R., Zhou, X. -J., Zhou, Y., Zhou, Z. -Y., Zhou, Z., Zhu, B., Zhu, C., Zhu, G. -Q., Zhu, H., Zhu, W. -G., Zhu, Y., Zhuang, H., Zhuang, X., Zientara-Rytter, K., Zimmermann, C. M., Ziviani, E., Zoladek, T., Zong, W. -X., Zorov, D. B., Zorzano, A., Zou, W., Zou, Z., Zuryn, S., Zwerschke, W., Brand-Saberi, B., Dong, X. C., Kenchappa, C. S., Lin, Y., Oshima, S., Rong, Y., Sluimer, J. C., Stallings, C. L., Tong, C. -K., and Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Programmed cell death, Settore BIO/06, Autophagosome, Autolysosome, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Autophagy-Related Proteins, Review, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Settore MED/04, 03 medical and health sciences, stress, Chaperone-mediated autophagy, ddc:570, Autophagy, LC3, Animals, Humans, cancer, Settore BIO/10, flux, lysosome, macroautophagy, neurodegeneration, phagophore, vacuole, Set (psychology), Molecular Biology, 030102 biochemistry & molecular biology, business.industry, Interpretation (philosophy), Autophagosomes, Cell Biology, Multicellular organism, 030104 developmental biology, Knowledge base, Biological Assay, Lysosomes, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Published: 2021

8. Tripartite relationship between gut microbiota, intestinal mucus and fibers: towards preventive strategies against enteric infections

Author: Tom Van de Wiele, Lucie Etienne-Mesmin, Pascale Mosoni, Stéphanie Blanquet-Diot, Adeline Sivignon, Christophe M. Courtin, Thomas Sauvaitre, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratoire Systèmes Communicants (SysCom), Laboratoire SYstèmes et Matériaux pour la MEcatronique (SYMME), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Lab Microbial Ecol & Technol LabMET, Universiteit Gent = Ghent University [Belgium] (UGENT), and Universiteit Gent = Ghent University (UGENT)
Subjects: Dietary Fiber, Gastrointestinal Diseases, [SDV]Life Sciences [q-bio], Disease, enteric pathogens, Biology, Gut flora, Health outcomes, dietary fibers, Microbiology, digestive system, 03 medical and health sciences, Human gut, mucus, Humans, Microbiome, 030304 developmental biology, 0303 health sciences, Intestinal mucus, gut microbiota, 030306 microbiology, biology.organism_classification, Mucus, 3. Good health, Gastrointestinal Microbiome, Intestines, Infectious Diseases, in vitro gut models, Digestive tract
Abstract: The human gut is inhabited by a large variety of microorganims involved in many physiological processes and collectively referred as to gut microbiota. Disrupted microbiome has been associated with negative health outcomes and especially could promote the onset of enteric infections. To sustain their growth and persistence within the human digestive tract, gut microbes and enteric pathogens rely on two main polysaccharide compartments, namely dietary fibers and mucus carbohydrates. Several evidences suggest that the three-way relationship between gut microbiota, dietary fibers and mucus layer could unravel the capacity of enteric pathogens to colonise the human digestive tract and ultimately lead to infection. The review starts by shedding light on similarities and differences between dietary fibers and mucus carbohydrates structures and functions. Next, we provide an overview of the interactions of these two components with the third partner, namely, the gut microbiota, under health and disease situations. The review will then provide insights into the relevance of using dietary fibers interventions to prevent enteric infections with a focus on gut microbial imbalance and impaired-mucus integrity. Facing the numerous challenges in studying microbiota–pathogen–dietary fiber-mucus interactions, we lastly describe the characteristics and potentialities of currently available in vitro models of the human gut.
Published: 2021

9. Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study

Author: Lucas Guillo, Benoit Flachaire, Jérôme Avouac, Catherine Dong, Maria Nachury, Guillaume Bouguen, Anthony Buisson, Ludovic Caillo, Mathurin Fumery, Cyrielle Gilletta, Xavier Hébuterne, Pierre Lafforgue, David Laharie, Emmanuel Mahé, Hubert Marotte, Stéphane Nancey, Sébastien Ottaviani, Jean-Hugues Salmon, Guillaume Savoye, Mélanie Serrero, Mathieu Uzzan, Manuelle Viguier, Christophe Richez, Laurent Peyrin-Biroulet, Philipe Seksik, Thao Pham, Philippe Ah-Soune, Nadia Arab, Laurent Beaugerie, Loïs Bolko, Joelle Bonnet, Yoram Bouhnik, Anne Bourrier, Franck Brazier, Franck Carbonnel, Maeva Charkaoui, Isabelle Charlot-Lambrecht, Antoine Chupin, Alice Combier, Marion Couderc, Fabienne Coury-Lucas, Ariadne Desjeux, Nicolas Duveau, Anne Grasland, Jean-Charles Grimaud, Xavier Guennoc, Cécilia Landman, Isabelle Nion-Larmurier, Catherien Leberre, Romain Leenhardt, Aude Le Goffic, Henri Montaudie, Jacques Morel, Thierry Passeron, Jeanne-Marie Perotin Collard, Elodie Poisnel, Vincent Pradel, Martin Soubrier, Harry Sokol, Eric Toussirot, Caroline Trang, My-Linh Trans Minh, Sophie Trijau, Frank Verhoeven, Stéphanie Viennot, Daniel Wendling, Hôpital Nord [CHU - APHM], Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-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 Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut du Mouvement et de l’appareil Locomoteur [Hôpital Sainte-Marguerite - APHM] (IML), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Victor Dupouy, Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Vieillissement, Fragilité (VIEFRA - EA 3797), Université de Reims Champagne-Ardenne (URCA), 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), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), 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), Hôpital Beaujon [AP-HP], Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Hôpital universitaire Robert Debré [Reims], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre International de Recherche en Infectiologie - UMR (CIRI), 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), and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Adult, Cohort Studies, Immunomodulating Agents, Crohn Disease, Immune-mediated inflammatory diseases, Hepatology, Gastroenterology, Humans, Tumor Necrosis Factor Inhibitors, Ustekinumab, Molecular targeted therapy, Combination therapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.
Published: 2023

10. Thoracic sarcopenia as a predictive factor of SARS-COV2 evolution

Author: J, Koehler, Y, Boirie, L, Bensid, B, Pereira, N, Ghelis, C, Dupuis, A, Tournadre, L, Boyer, L, Cassagnes, CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Male, Sarcopenia, SMI, Nutrition and Dietetics, SARS-CoV-2, SMD, Malnutrition, Middle Aged, Critical Care and Intensive Care Medicine, SARS-COV2, Humans, RNA, Viral, Female, Tomography, X-Ray Computed, Muscle, Skeletal, Covid-19, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Retrospective Studies, COVID
Abstract: Purpose: Evaluation of CT sarcopenia as a predictor of intensive care hospitalization during SARS-COV2 infection.Materials and methods: Single-center retrospective study of patients admitted to hospital with SARS-COV2 infection. The estimation of muscle mass (skeletal muscle index (SMI)) for sarcopenia, measure-ment of muscle density for muscle quality and body adiposity, were based on CT views on the T4 and L3 levels measured at admission. Demographic data, percentage of pulmonary parenchymal involvement as well as the orientation of patients during hospitalization and the risk of hospitalization in intensive care were collected.Results: A total of 162 patients hospitalized for SARS-COV2 infection were included (92 men and 70 women, with an average age of 64.6 years and an average BMI of 27.4). The muscle area measured at the level of L3 was significantly associated with the patient's unfavorable evolution (124.4cm2 [97; 147] vs 141.5 cm2 [108; 173]) (p 1/4 0.007), as was a lowered SMI (p < 0.001) and the muscle area measured in T4 (OR 1/4 0.98 [0.97; 0.99]), (p 1/4 0.026). Finally, an abdominal visceral fat area measured at the level of L3 was also associated with a risk of hospitalization in intensive care (249.4cm2 [173; 313] vs 147.5cm2 [93.1; 228] (p < 0.001).Conclusion: This study demonstrates that thoracic and abdominal sarcopenia are independently asso-ciated with an increased risk of hospitalization in an intensive care unit, suggesting the need to assess sarcopenia on admission during SARS-COV2 infection.
Published: 2022

11. A child is not an adult: development of a new in vitro model of the toddler colon

Author: Elora Fournier, Sylvain Denis, Alessandra Dominicis, Tom Van de Wiele, Monique Alric, Muriel Mercier-Bonin, Lucie Etienne-Mesmin, Stéphanie Blanquet-Diot, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), ToxAlim (ToxAlim), 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)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Superiore di Sanità (ISS), Center for Microbial Ecology and Technology (CMET), Universiteit Gent = Ghent University (UGENT), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), This work was supported by a grant from the French Ministère de l’Enseignement Supérieur et de la Recherche to EF and UMR MEDIS and by the National Research Institute for Agriculture, Food, and Environment (INRAE, France PlasToX project)., and ANR-21-CE34-0028,PLASTOX,Toxicité pour l'homme de micro- et nanoplastiques ingérés, en combinaison avec des polluants environnementaux métalliques(2021)
Subjects: Adult, Toddler, Colon, [SDV]Life Sciences [q-bio], Microbiota, Colonic model, Infant, Gut microbiota, General Medicine, Fatty Acids, Volatile, Applied Microbiology and Biotechnology, Mucus, Feces, Butyrates, Child, Preschool, Humans, Propionates, Child, Methane, Nutrition, Biotechnology
Abstract: International audience; Early life is a critical period where gut ecosystem and functions are being established with significant impact on health. For regulatory, technical, and cost reasons, in vitro gut models can be used as a relevant alternative to in vivo assays. An exhaustive literature review was conducted to adapt the Mucosal Artificial Colon (M-ARCOL) to specific physicochemical (pH, transit time, and nutritional composition of ileal effluents) and microbial parameters from toddlers in the age range of 6 months-3 years, resulting in the Tm-ARCOL. In vitro fermentations were performed to validate this newly developed colonic model compared to in vivo toddler data. Results were also compared to those obtained with the classical adult configuration. Fecal samples from 5 toddlers and 4 adults were used to inoculate bioreactors, and continuous fermentations were performed for 8 days. Gut microbiota structure (lumen and mucus-associated microbiota) and functions (gas and short-chain fatty acids) were monitored. Clearly distinct microbial signatures were obtained between the two in vitro conditions, with lower α-diversity indices and higher abundances of infant-related microbial populations (e.g., Bifidobacteriaceae, Enterobacteriaceae) in toddler versus adult conditions. In accordance with in vivo data, methane was found only in adult bioreactors, while higher percentage of acetate but lower proportions of propionate and butyrate was measured in toddlers compared to adults. This new in vitro model will provide a powerful platform for gut microbiome mechanistic studies in a pediatric context, both in nutritional- (e.g., nutrients, probiotics, prebiotics) and health-related (e.g., drugs, enteric pathogens) studies. KEY POINTS: • Development of a novel in vitro colonic model recapitulating the toddler environment. • Specific toddler versus adult digestive conditions are preserved in vitro. • The new model provides a powerful platform for microbiome mechanistic studies.
Published: 2022

12. Patterns of body weight change affect weight loss during a multidisciplinary intervention in adolescents with obesity

Author: Laurie, Isacco, Céline, Lambert, Nicole, Fearnbach, Alicia, Fillon, Julie, Masurier, Michael, Lowe, Leora, Benson, Martine, Duclos, Bruno, Pereira, Yves, Boirie, David, Thivel, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Clermont-Ferrand, Pennington Biomed Res Ctr, Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), UGECAM, Drexel University, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), and CHU Clermont-Ferrand-CHU Clermont-Ferrand
Subjects: Pediatric Obesity, Weight loss, Nutrition and Dietetics, Adolescent, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Body Weight, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Adolescents, Body Mass Index, Weight Reduction Programs, Weight variation, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Female, Obesity, Child, Retrospective Studies
Abstract: International audience; Aim: The current pediatric obesity health challenge necessitates a better understanding of the factors affecting weight loss success during interventions. The aim of this observational study was to test the impact of the rate of initial weight loss and body weight variability on weight loss during a 9-month residential, multidisciplinary weight loss program in adolescents with obesity. Methods: This retrospective study considered a whole sample of 510 adolescents with obesity (12-16 years, 435 girls). Body weight assessment was performed before (T0) and each week during the 9 months of a multidisci-plinary weight loss program. Initial weight change (week 4-W4) and overall weight change at week 12 (T1) and the end of the intervention (T2) were considered. Participants were divided into three groups (tertiles), based on their percentage of weight loss between T0 and W4; and weight variability was expressed by the root mean square error (RMSE) around each participant's regression line at each considered period (W4, T1, T2). Results: Adolescents with lower initial weight loss at W4 (tertile 3) displayed the lesser weight loss at T1 and T2 compared with adolescents in tertile 1 and 2. The RMSE was positively associated with the percentage of weight loss of the period considered, but when the analyses were adjusted for age and initial body weight, there was no more significant association.Conclusions: The rate of weight loss during the first few weeks is crucial for weight loss success, and weight variability is positively associated with weight loss in adolescents with obesity. Overall, results show that initial body weight is a determinant characteristic to consider during a lifestyle intervention. Further studies are thus needed to better understand the relationship between body weight change patterns and weight loss during the dynamic state that is adolescence.
Published: 2022

13. Association of protein-energy partitioning with body weight and body composition changes in adolescents with severe obesity

Author: Laurie Isacco, Stefano Lazzer, Bruno Pereira, Nicole Fearnbach, Christophe Montaurier, Michel Vermorel, Fabrice Rannou, Yves Boirie, David Thivel, Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Università degli Studi di Udine - University of Udine [Italie], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, Pennington Biomed Res Ctr, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Retraité, and Université Clermont Auvergne (UCA)
Subjects: Male, Pediatric Obesity, Nutrition and Dietetics, Adolescent, Nitrogen, Endocrinology, Diabetes and Metabolism, Body Weight, Medicine (miscellaneous), [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Obesity, Morbid, Weight Loss, Body Composition, Humans, Female, Child, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Background/Objectives Body composition and protein-energy partitioning changes are important factors of body weight regulation, but have not been studied in the context of clinical obesity treatment setting. Thus, the aim of the present study was to investigate the pattern of body weight loss, body composition, and energy partitioning changes during a 9-month multidisciplinary weight loss program and 4-month follow up and to test the associations among these changes in adolescents with severe obesity. Subjects/Methods Twenty-five adolescents (14.1 +/- 1.5 years old; 13 girls) with severe obesity joined a pediatric obesity center for a 9-month inpatient multidisciplinary weight loss program. All participants performed body composition assessment (i.e. fat mass-FM, and fat-free mass-FFM) and completed a 36-h session in indirect calorimetric chamber before the start (T0), at the end of the intervention (T1) and 4 months follow-up to the intervention (T2). The protein-energy partitioning (P ratio) was calculated as urinary nitrogen loss/total energy expenditure over 24 hours. Interventions 9-month individualized multidisciplinary weight loss program consisting of lifestyle education, psychological support, physical activity, and dietary intervention. Results Initial P ratio was positively associated with changes in body weight from T0 to T1 (p = 0.038). The changes in FFM/FM were negatively associated with body weight changes in boys (p = 0.006) from T0 to T1 and in girls (p < 0.001) from T1 to T2. Urinary nitrogen excretion (p < 0.001) and total energy expenditure (p < 0.001) significantly decreased during the weight loss program while the P ratio did not significantly change. Conclusion The present results suggest that baseline and changes in energy partitioning may be associated with changes in body weight in adolescents with severe obesity. In addition, sexual dimorphism in these patterns of change suggest the need for specific dietary and physical activity strategies in boys and girls to optimize body weight loss and to prevent or slow weight regain.
Published: 2022

14. Determinants of Resting Energy Expenditure in Very Old Nursing Home Residents

Author: Lahaye, Clément, Derumeaux-Burel, H., Guillet, C., Pereira, B., Boirie, Y., Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), and CHU Clermont-Ferrand-CHU Clermont-Ferrand
Subjects: Male, Resting energy expenditure, body composition, Nutrition and Dietetics, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, aging, Medicine (miscellaneous), Calorimetry, Indirect, malnutrition, Body Mass Index, Nursing Homes, Cross-Sectional Studies, inflammatory status, Humans, Female, Basal Metabolism, Geriatrics and Gerontology, Energy Metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Objectives This study aimed to measure resting energy expenditure (REE) in institutionalized old persons and to determine factors possibly related to change in REE as a basis for estimating energy requirements. Design and Settings A monocentric cross-sectional study was conducted. Statistical approaches were conducted to determine independent factors associated with REE. Various published predictive equations of REE were compared to our population. Participants 72 residents of a nursing home, mostly women (80.5%) aged 87.4 +/- 6.6 years were included. Measurements REE (indirect calorimetry), body composition (bio-impedance analysis), biological and anthropometric data were collected. Results Mean REE was 1006 +/- 181 kcal/d and was higher in men than in (1227 +/- 195 vs. 953 +/- 131 kcal/d, p 25 mg/l). Significant differences (p
Published: 2022

15. A 12-Week Cycling Workstation Intervention Improves Cardiometabolic Risk Factors in Healthy Inactive Office Workers

Author: Guirado, Terry, Metz, Lore, Pereira, Bruno, Brun, Carole, Birat, Anthony, Boscaro, Audrey, Bergouignan, Audrey, Thivel, David, Duclos, Martine, Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-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 Grenoble Alpes (UGA), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Biostat Unit DRCI, CHU Clermont-Ferrand, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Colorado Anschutz [Aurora], and Dept Sport Med and Funct Explorat
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Time Factors, sedentary time, primary prevention, Public Health, Environmental and Occupational Health, Cardiometabolic Risk Factors, cycling workstation, Risk Factors, cardiometabolic risk, light intensity physical activity, Humans, Sedentary Behavior, Workplace, Exercise
Abstract: International audience; Objectives The aim of this study was to evaluate the effects of a portable pedal machine intervention (60 minutes per working day) for 12 weeks on healthy tertiary employees' cardiometabolic risk factors. Methods Anthropometric parameters, body composition, cardiometabolic/inflammatory markers, physical fitness, physical activity, and sedentary time measured before and after the intervention were compared between office healthy workers who used a portable pedal machine (INT, n = 17) and those who did not (CTRL, n = 15). Results The INT group improved Delta ultrasensitive C-reactive protein (P = 0.008), Delta total cholesterol (P = 0.028), and Delta light-density lipoprotein cholesterol (P = 0.048) compared with the CTRL group (Delta: T1-T0). The intervention reduced daily sitting time (P
Published: 2022

16. Systematic Review on the Metabolic Interest of Glucosinolates and Their Bioactive Derivatives for Human Health

Author: Antonio Costa-Pérez, Vanesa Núñez-Gómez, Nieves Baenas, Giuseppe Di Pede, Mariem Achour, Claudine Manach, Pedro Mena, Daniele Del Rio, Cristina García-Viguera, Diego A. Moreno, Raúl Domínguez-Perles, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universidad de Murcia, Università degli studi di Parma = University of Parma (UNIPR), Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: clinical trials, Nutrition and Dietetics, bioactivity, epidemiological evidence, glucosinolates breakdown products metabolism bioactivity humans clinical trials epidemiological evidence, breakdown products, glucosinolates, humans, metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; In the last decade, most of the evidence on the clinical benefits of including cruciferous foods in the diet has been focused on the content of glucosinolates (GSL) and their corresponding isothiocyanates (ITC), and mercapturic acid pathway metabolites, based on their capacity to modulate clinical, biochemical, and molecular parameters. The present systematic review summarizes findings of human studies regarding the metabolism and bioavailability of GSL and ITC, providing a comprehensive analysis that will help guide future research studies and facilitate the consultation of the latest advances in this booming and less profusely researched area of GSL for food and health. The literature search was carried out in Scopus, PubMed and the Web of Science, under the criteria of including publications centered on human subjects and the use of Brassicaceae foods in different formulations (including extracts, beverages, and tablets), as significant sources of bioactive compounds, in different types of subjects, and against certain diseases. Twenty-eight human intervention studies met inclusion criteria, which were classified into three groups depending on the dietary source. This review summarizes recent studies that provided interesting contributions, but also uncovered the many potential venues for future research on the benefits of consuming cruciferous foods in our health and well-being. The research will continue to support the inclusion of GSL-rich foods and products for multiple preventive and active programs in nutrition and well-being.
Published: 2023

17. Early rehabilitation management strategy for septic arthritis of the knee

Author: Chabaud, A., Tetard, M., Descamps, S., Nguyen, C., Rannou, F., Tournadre, A., Lesens, O., Coudeyre, E., Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Centre Medico Infantile, Partenaires INRAE, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Arthritis, Infectious, Infectious Diseases, Knee Joint, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans
Abstract: International audience; Objectives: Early rehabilitation management of septic arthritis in the native knee is not standardized. In this context, it is necessary to develop and validate an early rehabilitation strategy.Materiel and methods: Based on the formalized HAS consensus method, a 4-phase rehabilitation strategy has been developed: recovery of joint amplitudes, muscle recovery without resistance, recovery with technical aid (crutches, canes), continuation of the rehabilitation (pursuit of muscle, articular, proprioceptive and endurance recovery).Results: It was submitted to the opinion of multidisciplinary experts (PMR, general practitioner, rheumatologist, infectiologist, orthopedic surgeon, physiotherapist). Nearly 80% of the items were directly validated, with only five items scoring less than 5/10. Modifications were made in order to obtain a final version of the protocol.Conclusion: Use of a rigorous methodology enabled a consensual strategy for early rehabilitation management to be developed. Prospective validation of this strategy is needed to confirm its feasibility and effectiveness.
Published: 2022

18. Safety, pharmacokinetic, and pharmacodynamic study of sibofimloc, a novel FimH blocker in patients with active Crohn's disease

Author: Walter Reinisch, Xavier Hébuterne, Anthony Buisson, Stefan Schreiber, Pierre Desreumaux, Christian Primas, Jean‐Michel Paillarse, Grégoire Chevalier, Christophe Bonny, Medizinische Universität Wien = Medical University of Vienna, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, CHU Lille, and Enterome
Subjects: Adult, clinical trials, Adhesins, Escherichia coli, Hepatology, FimH receptor, microbiology, Gastroenterology, microbiome, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, basic science, adherent-invasive E. coli, Anti-Bacterial Agents, Crohn's disease, Crohn Disease, FimH blocker, experimental models and pathophysiology, Escherichia coli, sibofimloc, Humans, Fimbriae Proteins, Biomarkers
Abstract: Essai clinique - Phase I; International audience; Background and aim: Expression of FimH adhesin by invasive Escherichia coli in the gastrointestinal tract of patients with Crohn's disease (CD) facilitates binding to epithelial glycoproteins and release of pro-inflammatory cytokines. Sibofimloc is a first-in-class FimH blocker that showed little systemic absorption in healthy volunteers. The current study evaluated systemic absorption, safety, and effect on inflammatory biomarkers of sibofimloc in patients with CD.Methods: This was an open-label, multicenter phase 1b study in adults with active CD. In part 1, two patients received a single oral dose of 3000-mg sibofimloc followed by 1500 mg b.i.d. for 13 days. In part 2, six patients received 1500-mg sibofimloc b.i.d. for 13 days. Blood was drawn for pharmacokinetic and biomarker analysis, and stool was collected for biomarker and microbiome analysis.Results: Eight patients with active ileal or ileocolonic CD were enrolled into the study. Systemic sibofimloc exposure was low. Sibofimloc was well tolerated with only grade 1-2 events observed. Several pro-inflammatory biomarkers, including IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and calprotectin, were decreased in stool by end of study.Conclusions: This first study of the novel FimH blocker, sibofimloc, in patients with active CD demonstrated minimal systemic exposure with good tolerance, while decreasing several inflammatory biomarkers. EudraCT number: 2017-003279-70.
Published: 2022

19. Chronic diseases are first associated with the degradation and artificialization of food matrices rather than with food composition: calorie quality matters more than calorie quantity

Author: A, Fardet, E, Rock, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Nutrient contents, Nutrition and Dietetics, Food synergy, The 3 V index, digestive, oral, and skin physiology, Medicine (miscellaneous), Diet, Food, Chronic diseases, Chronic Disease, Ultra-processed foods, Food matrix, Humans, Energy Intake, Nutritive Value, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Purpose For decades, it has been customary to relate human health to the nutritional composition of foods, and from there was born food composition databases, composition labelling scores and the recommendation to eat varied foods. However, individuals can fully address their nutritional needs and become chronically ill. The nutrient balance of a food is only a small part of its overall health potential. In this paper, we discussed the proof of concept that the increased risk of chronic diseases worldwide is primarily associated with the degradation and artificialization of food matrices, rather than only their nutrient contents, based on the assumption that "food matrices govern the metabolic fate of nutrients". Methods An empirico-inductive proof of concept research design has been used, based on scientific data linking the degree of food processing, food matrices and human health, notably on the glycaemic index, nutrient bioavailability, satiety potential, and synergistic effects. Results We postulate that if the nutrient content is insufficient to fully characterize the diet-global health relationship, one other dimensions is necessary, i.e., the food matrix through the degree of processing. Both matrix and nutrient composition dimensions have been included under the new concept of the 3V index for Real (Vrai), Vegetal (Vegetal), and Varied (Varie) foods. The Real metric, reflecting the integrity of the initial food matrix, is the most important, followed by the Vegetal (nutrient origin) and the Varied ("composition" effect) metrics. Conclusion Concerning their effects on health, food matrix comes first, and then nutrient composition, and calorie quality matters more than calorie quantity.
Published: 2022

20. Dietary modulation of large extracellular vesicles: the good and the bad for human health

Author: M Carmen Martinez, Laurent-Emmanuel Monfoulet, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Monfoulet, Laurent-Emmanuel
Subjects: microparticles, Nutrition and Dietetics, nutritional biomarkers, Medicine (miscellaneous), exosomes, human intervention studies, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, risk factor, Cell-Derived Microparticles, Humans, dietary constituents, diet, extracellular vesicles, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract: Extracellular vesicles (EVs) encompassing nanovesicles derived from the endosome system and generated by plasmatic membrane shedding are of increasing interest in view of their ability to sustain cell-to-cell communication and the possibility that they could be used as surrogate biomarkers of healthy and unhealthy trajectories. Nutritional strategies have been developed to preserve health, and the impact of these strategies on circulating EVs is arousing growing interest. Data available from published studies are now sufficient for a first integration to better understand the role of EVs in the relationship between diet and health. Thus, this review focuses on human intervention studies investigating the impact of diet or its components on circulating EVs. Because of analytical bias, only large EVs have been assessed so far. The analysis highlights that poor-quality diets with elevated fat and sugar content increase levels of circulating large EVs, and these can be partly counteracted by healthy food or some food micronutrients and bioactive compounds. However, knowledge of the content and the biological functions of these diet-induced EVs is still missing. It is important to address these aspects in new research in order to state if EVs are mediators of the effects of diet on health.
Published: 2021

21. Dynamics of extended-spectrum cephalosporin resistance genes in Escherichia coli from Europe and North America

Author: Zamudio, Roxana, Boerlin, Patrick, Beyrouthy, Racha, Madec, Jean-Yves, Schwarz, Stefan, Mulvey, Michael R, Zhanel, George G, Cormier, Ashley, Chalmers, Gabhan, Bonnet, Richard, Haenni, Marisa, Eichhorn, Inga, Kaspar, Heike, Garcia-Fierro, Raquel, Wood, James LN, Mather, Alison E, Quadram Institute, Biotechnology and Biological Sciences Research Council (BBSRC), University of Guelph, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Unité Antibiorésistance et Virulence Bactériennes (AVB), Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Freie Universität Berlin, Veterinary Centre for Resistance Research (TZR), Free University of Berlin (FU), Public Health Agency of Canada, University of Manitoba [Winnipeg], Federal Office of Consumer Protection and Food Safety, University of Cambridge [UK] (CAM), University of East Anglia [Norwich] (UEA), This project was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), through the Medical Research Council (MRC, MR/R000948/1) [R.Z., J.L.N.W., A.E.M.], the Canadian Institutes of Health Research (CFC-150770) [A.C., G.C., P.B.], and the Genomics Research and Development Initiative (Government of Canada) [M.R.M.], the German Federal Ministry of Education and Research (BMBF) grant no. 01KI1709 [I.E., H.K., S.S.], the French Agency for food environmental and occupational health & safety (Anses) [R.G.F., M.H., J.Y.M.], and the French National Reference Center (CNR) for antimicrobial resistance [R. Beyrouthy, R. Bonnet]. Support was also provided by the Biotechnology and Biological Sciences Research Council (BBSRC) through the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10348 (Theme 1, Epidemiology and Evolution of Pathogens in the Food Chain) [R.Z., A.E.M.]., European Project: JPI-EC-AMR, European Project: 323209,EC:FP7:HEALTH,FP7-JPROG-2012-RTD,JPIAMR(2012), Zamudio, Roxana [0000-0003-3634-4828], Schwarz, Stefan [0000-0002-6303-8212], Chalmers, Gabhan [0000-0002-6651-4253], Wood, James LN [0000-0002-0258-3188], Mather, Alison E [0000-0001-6513-3515], and Apollo - University of Cambridge Repository
Subjects: Multidisciplinary, Cephalosporin Resistance, General Physics and Astronomy, 500 Naturwissenschaften und Mathematik::570 Biowissenschaften, Biologie::570 Biowissenschaften, Biologie, General Chemistry, Antimicrobial resistance, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, beta-Lactamases, General Biochemistry, Genetics and Molecular Biology, Anti-Bacterial Agents, Cephalosporins, Bacterial genetics, Escherichia coli, Animals, Humans, Bacterial genomics, Phylogeny, Escherichia coli Infections, Plasmids
Abstract: Funder: Genomics Research and Development Initiative (Government of Canada), the German Federal Ministry of Education and Research (BMBF) grant no. 01KI1709, the French Agency for food environmental and occupational health & safety (Anses), and the French National Reference Center (CNR) for antimicrobial resistance., Extended-spectrum cephalosporins (ESCs) are critically important antimicrobial agents for human and veterinary medicine. ESC resistance (ESC-R) genes have spread worldwide through plasmids and clonal expansion, yet the distribution and dynamics of ESC-R genes in different ecological compartments are poorly understood. Here we use whole genome sequence data of Enterobacterales isolates of human and animal origin from Europe and North America and identify contrasting temporal dynamics. AmpC β-lactamases were initially more dominant in North America in humans and farm animals, only later emerging in Europe. In contrast, specific extended-spectrum β-lactamases (ESBLs) were initially common in animals from Europe and later emerged in North America. This study identifies differences in the relative importance of plasmids and clonal expansion across different compartments for the spread of different ESC-R genes. Understanding the mechanisms of transmission will be critical in the design of interventions to reduce the spread of antimicrobial resistance.
Published: 2022

22. Metaproteomics Approach and Pathway Modulation in Obesity and Diabetes: A Narrative Review

Author: Francesco Maria, Calabrese, Annalisa, Porrelli, Mirco, Vacca, Blandine, Comte, Katharina, Nimptsch, Mariona, Pinart, Tobias, Pischon, Estelle, Pujos-Guillot, Maria, De Angelis, Department of Biology [University of Bari], Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany, MetaboHUB-Clermont, MetaboHUB, and Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, 70126 Bari, Italy
Subjects: Adult, Male, Proteomics, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], obesity, Adolescent, Review, metabolic diseases, Feces, Young Adult, Bacterial Proteins, low-grade inflammation, Humans, TX341-641, Child, Aged, Aged, 80 and over, Inflammation, diabetes, gut microbiota, Nutrition. Foods and food supply, Middle Aged, Gastrointestinal Microbiome, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Child, Preschool, Dysbiosis, Female, metaproteomics
Abstract: International audience; Low-grade inflammatory diseases revealed metabolic perturbations that have been linked to various phenotypes, including gut microbiota dysbiosis. In the last decade, metaproteomics has been used to investigate protein composition profiles at specific steps and in specific healthy/pathologic conditions. We applied a rigorous protocol that relied on PRISMA guidelines and filtering criteria to obtain an exhaustive study selection that finally resulted in a group of 10 studies, based on metaproteomics and that aim at investigating obesity and diabetes. This batch of studies was used to discuss specific microbial and human metaproteome alterations and metabolic patterns in subjects affected by diabetes (T1D and T2D) and obesity. We provided the main up- and down-regulated protein patterns in the inspected pathologies. Despite the available results, the evident paucity of metaproteomic data is to be considered as a limiting factor in drawing objective considerations. To date, ad hoc prepared metaproteomic databases collecting pathologic data and related metadata, together with standardized analysis protocols, are required to increase our knowledge on these widespread pathologies.
Published: 2022

23. Association between Metabolic Syndrome Diagnosis and the Physical Activity—Sedentary Profile of Adolescents with Obesity: A Complementary Analysis of the Beta-JUDO Study

Author: Valérie Julian, Iris Ciba, Roger Olsson, Marie Dahlbom, Dieter Furthner, Julian Gomahr, Katharina Maruszczak, Katharina Morwald, Thomas Pixner, Anna Schneider, Bruno Pereira, Martine Duclos, Daniel Weghuber, David Thivel, Peter Bergsten, Anders Forslund, Service Médecine du Sport et Explorations Fonctionnelles [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Male, Adolescent, [SDV]Life Sciences [q-bio], education, pediatric obesity, sedentary time, physical activity, Blood Pressure, Cardiovascular System, Article, metabolic syndrome, Body Mass Index, Risk Factors, cardiometabolic risk, Accelerometry, Humans, TX341-641, Child, Exercise, Sport and Fitness Sciences, Triglycerides, Julian, Nutrition and Dietetics, Idrottsvetenskap, Nutrition. Foods and food supply, Cholesterol, HDL, Public Health, Global Health, Social Medicine and Epidemiology, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cardiovascular Diseases, Regression Analysis, Female, Insulin Resistance, Sedentary Behavior, Waist Circumference, human activities, Food Science
Abstract: Metabolic syndrome (MetS) is highly prevalent in children and adolescents with obesity and places them at an increased risk of cardiovascular-related diseases. However, the associations between objectively measured movement-related behaviors and MetS diagnosis remain unexplored in youths with obesity. The aim was to compare profiles of sedentary (SED) time (more sedentary, SED+ vs. less sedentary, SED−), moderate to vigorous physical activity (MVPA) time (more active, MVPA+ vs. less active, MVPA−) and combinations of behaviors (SED−/MVPA+, SED−/MVPA−, SED+/MVPA+, SED+/MVPA−) regarding the MetS diagnosis. One hundred and thirty-four adolescents with obesity (13.4 ± 2.2 years) underwent 24 h/7 day accelerometry, waist circumference (WC), blood pressure (BP), high-density lipoprotein-cholesterol (HDL-c), triglycerides (TG) and insulin-resistance (IR) assessments. Cumulative cardiometabolic risk was assessed by using (i) MetS status (usual dichotomic definition) and (ii) cardiometabolic risk z-score (MetScore, mean of standardized WC, BP, IR, TG and inverted HDL-c). SED− vs. SED+ and MVPA+ vs. MVPA− had lower MetS (p < 0.01 and p < 0.001) and MetScore (p < 0.001). SED−/MVPA+ had the lowest risk. While SED and MVPA times were lower in SED−/MVPA− vs. SED+/MVPA+ (p < 0.001), MetScore was lower in SED−/MVPA− independently of body mass index (BMI) (p < 0.05). MVPA, but not SED, time was independently associated with MetS diagnosis (p < 0.05). Both MVPA (p < 0.01) and SED times (p < 0.05) were associated with MetScore independently of each other. A higher MVPA and lower SED time are associated with lower cumulative cardiometabolic risk.
Published: 2022

24. Alternative in vitro models used in the main safety tests of cosmetic products and new challenges

Author: Edith Filaire, Rachida Nachat‐Kappes, Camille Laporte, Marie‐Françoise Harmand, Marina Simon, Christian Poinsot, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Icare, InnovSkin, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Aging, skin, Pharmaceutical Science, in vitro, skin-on-a-chip, Cosmetics, Dermatology, In Vitro Techniques, Animal Testing Alternatives, Colloid and Surface Chemistry, Consumer Product Safety, Chemistry (miscellaneous), chemical analysis, Drug Discovery, Animals, Humans, three-dimensional skin cell model, [CHIM]Chemical Sciences, toxicology
Abstract: Guided by ethical considerations and regulatory requirements such as the 7th Amendment to the European Cosmetics Directive N° 1223/2009, the cosmetic industry has developed and evaluated alternative test strategies such as in vitro assays, in silico approaches for toxicological endpoints and efficacy of cosmetic products and cosmetics ingredients. In consequence, the European Centre for the Validation of Alternative Methods (ECVAM) has proposed a list of validated cell-based in vitro models for predicting the safety and toxicity of cosmetic ingredients. These models have been demonstrated as valuable and effective tools to overcome the limitations of animal in vivo studies. For example, 3D human skin equivalent models are used to evaluate skin irritation potential; and excised human skin is used as the gold standard for the evaluation of dermal absorption.This review presents, in relation to the regulatory requirements, the main alternative in vitro models used in the safety tests of cosmetic products, focusing on skin sensitization, skin corrosion, skin irritation and skin absorption, with advantages and limitations of each model. Recent innovative 3D cell technologies such as Organ-on-a-Chip (OoC) models that can bring significant improvements for toxicology and efficacy testing are also presented.The development of OoC technology is promising for assessing the toxicity of substances contained in cosmetics, particularly for repeated dose toxicity, for which no alternative in vitro methods are currently available. Nevertheless, aside from the challenges, the technology needs to be validated and accepted by regulatory organizations as an effective method. Collaboration between researchers, regulatory organizations and industry would be required to achieve this validation.Guidée par des considérations éthiques et des exigences réglementaires telles que le 7e amendement à la directive européenne sur les cosmétiques N° 1223/2009, l'industrie cosmétique a développé et évalué des stratégies de test alternatives telles que des tests in vitro, des approches in silico pour les paramètres toxicologiques et l'efficacité des produits cosmétiques et ingrédients cosmétiques. En conséquence, le Centre Européen pour la Validation des Méthodes Alternatives (ECVAM) a proposé une liste de modèles cellulaires in vitro validés pour prédire la sécurité et la toxicité des ingrédients cosmétiques. Ces modèles ont été démontrés comme des outils précieux et efficaces pour surmonter les limites des études animales in vivo. Par exemple, des modèles équivalents de peau humaine 3D sont utilisés pour évaluer le potentiel d'irritation de la peau; et la peau humaine excisée est utilisée comme « gold standard » pour l'évaluation de l'absorption cutanée.Cette revue présente, en lien avec les exigences réglementaires, les principaux modèles alternatifs in vitro utilisés dans les tests de sécurité des produits cosmétiques, en se concentrant sur la sensibilisation, la corrosion, l'irritation et l'absorption cutanée, avec les avantages et les limites de chaque modèle. Des technologies cellulaires 3D innovantes récentes telles que les modèles Organ-on-a-Chip (OoC) qui peuvent apporter des améliorations significatives pour la toxicologie et les tests d'efficacité sont également présentées.Le développement de la technologie OoC est prometteur pour évaluer la toxicité des substances contenues dans les cosmétiques, en particulier pour la toxicité à doses répétées, pour laquelle aucune méthode alternative in vitro n'est actuellement disponible. Néanmoins, outre les défis, la technologie doit être validée et acceptée par les organismes régulateurs comme une méthode efficace. Une collaboration entre les chercheurs, les organismes régulateurs et l'industrie serait nécessaire pour parvenir à cette validation.
Published: 2022

25. A Scoping Review: Metabolomics Signatures Associated with Animal and Plant Protein Intake and Their Potential Relation with Cardiometabolic Risk

Author: Gaïa Lépine, Didier Rémond, Jean-François Huneau, François Mariotti, Hélène Fouillet, Sergio Polakof, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914)), and AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Mediterranean diet, legumes, nutrimetabolomics, dietary patterns, Medicine (miscellaneous), 030209 endocrinology & metabolism, Review, Gut flora, Bioinformatics, meat, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Metabolomics, vegetable proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Diabetes mellitus, Aromatic amino acids, medicine, Animals, Humans, metabolites, Plant Proteins, 2. Zero hunger, Cardiometabolic risk, chemistry.chemical_classification, amino acids, 030109 nutrition & dietetics, Nutrition and Dietetics, diabetes, biology, medicine.disease, biology.organism_classification, Diet, 3. Good health, Amino acid, chemistry, Cardiovascular Diseases, Plant protein, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Food Science
Abstract: International audience; The dietary shift from animal protein (AP) to plant protein (PP) sources is encouraged for both environmental and health reasons. For instance, PPs are associated with lower cardiovascular and diabetes risks compared with APs, although the underlying mechanisms mostly remain unknown. Metabolomics is a valuable tool for globally and mechanistically characterizing the impact of AP and PP intake, given its unique ability to provide integrated signatures and specific biomarkers of metabolic effects through a comprehensive snapshot of metabolic status. This scoping review is aimed at gathering and analyzing the available metabolomics data associated with PP- and AP-rich diets, and discusses the metabolic effects underlying these metabolomics signatures and their potential implication for cardiometabolic health. We selected 24 human studies comparing the urine, plasma, or serum metabolomes associated with diets with contrasted AP and PP intakes. Among the 439 metabolites reported in those studies as able to discriminate AP- and PP-rich diets, 46 were considered to provide a robust level of evidence, according to a scoring system, especially amino acids (AAs) and AA-related products. Branched-chain amino acids, aromatic amino acids (AAAs), glutamate, short-chain acylcarnitines, and trimethylamine-N-oxide, which are known to be related to an increased cardiometabolic risk, were associated with AP-rich diets, whereas glycine (rather related to a reduced risk) was associated with PP-rich diets. Tricarboxylic acid (TCA) cycle intermediates and products from gut microbiota AAA degradation were also often reported, but the direction of their associations differed across studies. Overall, AP- and PP-rich diets result in different metabolomics signatures, with several metabolites being plausible candidates to explain some of their differential associations with cardiometabolic risk. Additional studies specifically focusing on protein type, with rigorous intake control, are needed to better characterize the associated metabolic phenotypes and understand how they could mediate differential AP and PP effects on cardiometabolic risk.
Published: 2021

26. SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases

Author: Anja Strangfeld, Ana M. Rodrigues, Loreto Carmona, Ludovic Trefond, Charalampos Papagoras, Laure Gossec, N Roux, Kimme L. Hyrich, Saskia Lawson-Tovey, Bernd Raffeiner, Elsa F Mateus, Gözde Kübra Yardımcı, Pedro Machado, Xavier Mariette, NIHR Manchester Biomedical Research Centre [Manchester] (BRC [Manchester]), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Centre for Genetics and Genomics Versus Arthritis, Centre for Epidemiology Versus Arthritis, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Instituto de Salud Musculoesqueletica (InMusc), Central Hospital of Bolzano, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital privé Robert-Schuman, Metz, France., Sociedade Portuguesa de Reumatologia [Lisboa], Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Democritus University of Thrace (DUTH), Liga Portuguesa Contra as Doenças Reumaticas (LPCDR), EULAR PARE [Zurich, Switzerland], Université Paris-Saclay, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, University College of London [London] (UCL), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University College London Hospitals (UCLH), London North West University Healthcare NHS Trust (LNWH), European Alliance of Associations for Rheumatology, Service de Rhumatologie [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Molé, Christine
Subjects: Male, medicine.medical_specialty, COVID-19 Vaccines, Immunology, Population, Comorbidity, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Rheumatic Diseases, Internal medicine, Epidemiology, medicine, Humans, Immunology and Allergy, Registries, Adverse effect, education, Aged, Aged, 80 and over, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, education.field_of_study, business.industry, Abatacept, COVID-19, Middle Aged, vaccination, Vaccine efficacy, Vaccination, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Hypertension, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, epidemiology, Rituximab, business, medicine.drug
Abstract: Patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs) are often treated with immunomodulatory or immunosuppressive medications; consequently, they have been excluded alongside other immunocompromised patients from late stages of SARS-CoV-2 vaccine trials. SARS-CoV-2 vaccine efficacy in this population is unclear, though initial data are reassuring overall. However, a slightly lower SARS-CoV-2 immunogenicity of vaccines has been documented in some patients with iRMD.1 2 Some common rheumatic and musculoskeletal disease (RMD) medications have been highlighted as possible influential factors on immunogenicity, particularly rituximab (RTX), mycophenolate mofetil (MMF), methotrexate (MTX), abatacept and glucocorticoids.3–7 The European Alliance of Associations for Rheumatology (EULAR) launched a COVID-19 registry in March 2020, capturing COVID-19 outcomes in the European RMD population. Questions on reinfection and vaccination were added in January 2021. A further EULAR registry (COVAX) was launched in February 2021 to collect data on COVID-19 vaccination and related adverse events among patients with RMD. Here we describe a series of patients who contracted SARS-CoV-2 infection after COVID-19 vaccination between 19 January 2021 and 27 July 2021. The series consists of 38 adults with iRMDs, 8 from the COVID-19 registry (
Published: 2021

27. Vitamin D status modulates mitochondrial oxidative capacities in skeletal muscle: role in sarcopenia

Author: Jérôme Salles, Audrey Chanet, Christelle Guillet, Anouk MM. Vaes, Elske M. Brouwer-Brolsma, Christophe Rocher, Christophe Giraudet, Véronique Patrac, Emmanuelle Meugnier, Christophe Montaurier, Philippe Denis, Olivier Le Bacquer, Adeline Blot, Marion Jourdan, Yvette Luiking, Matthew Furber, Miriam Van Dijk, Nicolas Tardif, Y. Yves Boirie, Stéphane Walrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Wageningen University and Research [Wageningen] (WUR), Laboratoire de biogenèse membranaire (LBM), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-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 de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Danone Nutricia Research [Utrecht], Karolinska University Hospital [Stockholm], Salles, Jérôme, Université de Bordeaux (UB), Department of Earth Sciences [UNH Durham], University of New Hampshire (UNH), CHU Clermont-Ferrand, and Karolinska University Hospital [Solna, Sweden] (KUH)
Subjects: Global Nutrition, Wereldvoeding, Sarcopenia, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Vitamin D Deficiency, General Biochemistry, Genetics and Molecular Biology, Rats, Mitochondria, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Mice, Oxidative Stress, Humans, Animals, Life Science, Vitamin D, Muscle, Skeletal, General Agricultural and Biological Sciences, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Aged
Abstract: Skeletal muscle mitochondrial function is the biggest component of whole-body energy output. Mitochondrial energy production during exercise is impaired in vitamin D-deficient subjects. In cultured myotubes, loss of vitamin D receptor (VDR) function decreases mitochondrial respiration rate and ATP production from oxidative phosphorylation. We aimed to examine the effects of vitamin D deficiency and supplementation on whole-body energy expenditure and muscle mitochondrial function in old rats, old mice, and human subjects. To gain further insight into the mechanisms involved, we used C2C12 and human muscle cells and transgenic mice with muscle-specific VDR tamoxifen-inducible deficiency. We observed that in vivo and in vitro vitamin D fluctuations changed mitochondrial biogenesis and oxidative activity in skeletal muscle. Vitamin D supplementation initiated in older people improved muscle mass and strength. We hypothesize that vitamin D supplementation is likely to help prevent not only sarcopenia but also sarcopenic obesity in vitamin D-deficient subjects.
Published: 2022

28. Peripheral Amino Acid Appearance Is Lower Following Plant Protein Fibre Products, Compared to Whey Protein and Fibre Ingestion, in Healthy Older Adults despite Optimised Amino Acid Profile

Author: Elena de Marco Castro, Giacomo Valli, Caroline Buffière, Christelle Guillet, Brian Mullen, Jedd Pratt, Katy Horner, Susanne Naumann-Gola, Stephanie Bader-Mittermaier, Matteo Paganini, Giuseppe De Vito, Helen M. Roche, Dominique Dardevet, University College Dublin [Dublin] (UCD), Università degli Studi di Padova = University of Padua (Unipd), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Fraunhofer (Fraunhofer-Gesellschaft), Department of Biomedical Sciences [Padova, Italy] (Neuroscience Institute), Università degli Studi di Padova = University of Padua (Unipd)-Italian National Research Council [Padova, Italy], and Publica
Subjects: Male, Sarcopenia, [SDV]Life Sciences [q-bio], aminoacidemia, digestibility, fibre, plant protein, sarcopenia, Plant protein, Fibre, Eating, Leucine, Aminoacidemia, Animals, Humans, Insulin, Single-Blind Method, Amino Acids, Plant Proteins, Aged, Nutrition and Dietetics, Postprandial Period, Whey Proteins, Digestibility, Female, Dietary Proteins, Food Science
Abstract: International audience; Plant-based proteins are generally characterised by lower Indispensable Amino Acid (IAA) content, digestibility, and anabolic properties, compared to animal-based proteins. However, they are environmentally friendlier, and wider consumption is advocated. Older adults have higher dietary protein needs to prevent sarcopenia, a disease marked by an accelerated loss of muscle mass and function. Given the lower environmental footprint of plant-based proteins and the importance of optimising dietary protein quality among older adults, this paper aims to assess the net peripheral Amino Acid (AA) appearance after ingestion of three different plant protein and fibre (PPF) products, compared to whey protein with added fibre (WPF), in healthy older adults. In a randomised, single-blind, crossover design, nine healthy men and women aged ≥65 years consumed four test meals balanced in AA according to the FAO reference protein for humans, matched for leucine, to optimally stimulate muscle protein synthesis in older adults. A fasted blood sample was drawn at each visit before consuming the test meal, followed by postprandial arterialise blood sampling every 30 min for 3 h. The test meal was composed of a soup containing either WPF or PPF 1–3. The PPF blends comprised pea proteins with varying additional rice, pumpkin, soy, oat, and/or almond protein. PPF product ingestion resulted in a lower maximal increase of postprandial leucine concentration and the sum of branched-chain AA (BCAA) and IAA concentrations, compared to WPF, with no effect on their incremental area under the curve. Plasma methionine and cysteine, and to a lesser extent threonine, appearance were limited after consuming the PPF products, but not WPF. Despite equal leucine doses, the WPF induced greater postprandial insulin concentrations than the PPF products. In conclusion, the postprandial appearance of AA is highly dependent on the protein source in older adults, despite providing equivalent IAA levels and dietary fibre. Coupled with lower insulin concentrations, this could imply less anabolic potential. Further investigation is required to understand the applicability of plant-based proteins in healthy older adults.
Published: 2022

29. Role of megaplasmids and chromosomal integration in acquisition of CTX-M-encoding genes by Pseudomonas aeruginosa

Author: Pauline Triponney, Maxime Bour, Racha Beyrouthy, Richard Bonnet, Patrick Plésiat, Katy Jeannot, Centre National de Référence de la Résistance aux Antibiotiques (CNR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Bactériologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Bactériologie [CHRU Besançon], and Santé Publique France
Subjects: Pharmacology, Microbiology (medical), Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Genes, Viral, Genes, Bacterial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pseudomonas aeruginosa, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, Pharmacology (medical), Pseudomonas Infections
Abstract: International audience
Published: 2022

30. Flavanol Consumption in Healthy Men Preserves Integrity of Immunological-Endothelial Barrier Cell Functions:Nutri(epi)genomic Analysis

Author: Dragan Milenkovic, Ana Rodriguez‐Mateos, Margarete Lucosz, Geoffrey Istas, Ken Declerck, Roberto Sansone, René Deenen, Karl Köhrer, Karla Fabiola Corral‐Jara, Joachim Altschmied, Judith Haendeler, Malte Kelm, Wim Vanden Berghe, Christian Heiss, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), University of California [Davis] (UC Davis), University of California (UC), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], King‘s College London, University of Antwerp (UA), Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] (IUF), and University of Surrey (UNIS)
Subjects: Male, Flavonols, 1.1 Normal biological development and functioning, Blood Pressure, Cardiovascular, Rare Diseases, Food Sciences, Double-Blind Method, Clinical Research, Underpinning research, Genetics, genomics, Humans, Cacao, Nutrition and Dietetics, DNA methylation, Nutrition & Dietetics, Pharmacology. Therapy, Human Genome, Polyphenols, clinical trial, epicatechin, Middle Aged, Good Health and Well Being, cocoa flavanol, Public Health and Health Services, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science, Biotechnology
Abstract: International audience; Scope While cocoa flavanol (CF) consumption improves cardiovascular risk biomarkers, molecular mechanisms underlying their protective effects are not understood. Objective To investigate nutri(epi)genomic effects of CF and identify regulatory networks potential mediating vascular health benefits. Methods and Results Twenty healthy middle-aged men consume CF (bi-daily 450 mg) or control drinks for 1 month. Microarray analysis identifies 2235 differentially expressed genes (DEG) involved in processes regulating immune response, cell adhesion, or cytoskeleton organization. Distinct patterns of DEG correlate with CF-related changes in endothelial function, arterial stiffness, and blood pressure. DEG profile negatively correlates with expression profiles of cardiovascular disease patients. CF modulated DNA methylation profile of genes implicates in cell adhesion, actin cytoskeleton organization, or cell signaling. In silico docking analyses indicate that CF metabolites have the potential of binding to cell signaling proteins and transcription factors. Incubation of plasma obtained after CF consumption decrease monocyte to endothelial adhesion and dose-dependently increase nitric oxide-dependent chemotaxis of circulating angiogenic cells further validating the biological functions of CF metabolites. Conclusion In healthy humans, CF consumption may mediate vascular protective effects by modulating gene expression and DNA methylation towards a cardiovascular protective effect, in agreement with clinical results, by preserving integrity of immunological-endothelial barrier functions.
Published: 2022

31. Identification of Responders to Balneotherapy among Adults over 60 Years of Age with Chronic Low Back Pain: A Pilot Study with Trajectory Model Analysis

Author: Benjamin Raud, Charlotte Lanhers, Cindy Crouzet, Bénédicte Eschalier, François Bougeard, Anna Goldstein, Bruno Pereira, Emmanuel Coudeyre, Service de Médecine Physique et de Réadaptation [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Adult, Male, Balneology, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, balneotherapy, Pilot Projects, Middle Aged, Cohort Studies, aged, hydrotherapy, disability, [SDE]Environmental Sciences, chronic low back pain, Humans, Female, Prospective Studies, Low Back Pain
Abstract: Balneotherapy may be a relevant treatment for chronic low back pain (LBP) in individuals > 60 years old. This pilot study aimed to determine the effectiveness of balneotherapy for chronic LBP in people > 60 years old and to determine profiles of responders with trajectory model analysis. This was a pilot prospective open cohort study, with repeated measurements using validated questionnaires; participants were their own controls. The primary endpoint was the proportion of participants with a change in pain intensity between the start of treatment and 3 months after treatment assessed with a numeric scale (NS) from 0 to 100 mm, with an effect size (ES) > 0.5. The assessments involved questionnaires that were self-administered on days (D) 1 and 21 and at months 3 and 6. The secondary objective was to determine the profile of responders to balneotherapy. We included 78 patients (69.2% women), mean age 68.3 ± 5.3 years. The mean pain score on the NS was 48.8 ± 19.9 at D1 and 39.1 ± 20.5 at 3 months (p < 0.001). The ES was 0.47 [95% confidence interval [CI] 0.25 to 0.69] for the whole sample; 36% (28/78) had an ES > 0.5; 23% (18/78) had a moderate ES (0 to 0.5); and 41% (32/78) had an ES of zero (14/78) or < 0 (18/78), corresponding to increased pain intensity. The pain trajectory model showed that the change in pain between D1 and D21 for trajectory A (larger reduction in pain intensity) was −50% [95% CI −60 to −27], and for trajectory B (smaller reduction in pain intensity), it was −13% [−33 to 0] (p < 0.001). Between Day 1 and month 3, the change for trajectory A was −33% [−54; 0] and for trajectory B was −13% [−40 to 0] (p = 0.14). Finally, between D1 and month 6, the change for trajectory A was −50% [−60 to 0] and for trajectory B was −6% [−33 to 17] (p = 0.007). The patients in trajectory A reported performing more physical activity than those in trajectory B (p = 0.04). They were also less disabled, with a mean Oswestry Disability Index of 40.4 versus 45.7 for those in trajectory A and B, respectively, (p = 0.03) and had a higher total Arthritis Self-Efficacy Scale score. This real-life study of the effectiveness of balneotherapy on chronic LBP identified distinct pain trajectories and predictive variables for responders. These criteria could be used in decision-making regarding the prescription of balneotherapy, to ensure personalized management of chronic LBP.
Published: 2022

32. Editorial: Women in science: Occupational health and safety 2021

Author: Ledda, Caterina, Duclos, Martine, Martínez-Jarreta, Begoña, Univ. Degli Studi di Catania (DIEES), Università degli studi di Catania = University of Catania (Unict), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and University of Zaragoza - Universidad de Zaragoza [Zaragoza]
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Science, Public Health, Environmental and Occupational Health, Humans, Female, Safety, Occupational Health, Women, Working
Abstract: Editorial Material; International audience
Published: 2022

33. There is a need for a complete consideration of overall movement behaviors for the prevention, treatment, and follow-up of cancer risks and patients

Author: Gaël Ennequin, Lidia Delrieu, Adrien Rossary, Quentin Jacquinot, Fabienne Mougin, David Thivel, Martine Duclos, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Residual Tumor & Response to Treatment Laboratory [Paris] (RT2Lab), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut Régional Fédératif du Cancer (IRFC), Université de Bourgogne (UB), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and CHU Clermont-Ferrand
Subjects: treatment, Health Behavior, Public Health, Environmental and Occupational Health, physical activity, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, prevention, sedentary behavior, Neoplasms, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], cancer, Humans, Exercise, Follow-Up Studies
Abstract: International audience; No abstract available
Published: 2022

34. Development of the Children and Adolescents Physical Activity and Sedentary Questionnaire (CAPAS-Q): Psychometric Validity and Clinical Interpretation

Author: Alicia Fillon, Bruno Pereira, Jérémy Vanhelst, Joanna Baran, Julie Masurier, Terry Guirado, Yves Boirie, Martine Duclos, Valérie Julian, David Thivel, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Rzeszow University, UGECAM, Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Université Clermont Auvergne (UCA), and Observatoire national de l’activité physique et de la sédentarité (ONAPS)
Subjects: Adolescent, Psychometrics, Health, Toxicology and Mutagenesis, questionnaire, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, physical activity, Reproducibility of Results, physical activity sedentary behaviors children adolescents questionnaire, sedentary behaviors, children, adolescents, Surveys and Questionnaires, Accelerometry, Humans, Child, Exercise
Abstract: Background: Pediatricians’ clinical practice and health interventions in youths require instruments with adequate psychometric properties to assess physical activity (PA), sedentary behaviors (SB), and their subdomains. Objective: To assess the psychometric properties of the Children and Adolescents Physical Activity and Sedentary-Questionnaire (CAPAS-Q) in healthy French children and adolescents. Methods: The CAPAS-Q has been developed through a rigorous collective procedure and consists of a 31 items self-administered questionnaire evaluating children’s 7-day PA and SB dimensions and subdomains. Participants (n = 103, aged 8–18 years old) completed the questionnaire twice (7 days apart) and wore an ActiGraph GT3X+ accelerometer for 7 days. Anthropometric measurements and body composition were assessed. Results: Cronbach alpha for PA and SB dimensions were 0.71 and 0.68, respectively. Reproducibility was found moderate to good, with Lin’s coefficients of 0.69 and 0.68 for PA and SB dimensions, respectively. Reproducibility was higher for adolescents compared to children. PA dimension was positively correlated with moderate PA, vigorous PA, moderate to vigorous PA, and total PA times and negatively correlated with SB time (p < 0.05). SB dimension and screen time were positively correlated with SB time and negatively correlated with LPA, MPA, MVPA, and total PA times (p < 0.05). Spearman correlation coefficients were fair to moderate, ranging between 0.23–0.45. Conclusion: The CAPAS-Q proposes a reliable and valid evaluation of French children and adolescents’ PA and SB, providing clinicians with potential intervention levels to improve youth movement behaviors.
Published: 2022

35. An adherent-invasive Escherichia coli-colonized mouse model to evaluate microbiota-targeting strategies in Crohn's disease

Author: Adeline Sivignon, Mélissa Chervy, Caroline Chevarin, Elia Ragot, Elisabeth Billard, Jérémy Denizot, Nicolas Barnich, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut Universitaire de Technologie en Génie Biologique [Aubière, France] (IUTGB), and ROSSI, Sabine
Subjects: Microbiota, Neuroscience (miscellaneous), Medicine (miscellaneous), Mice, Transgenic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ileal colonization, Bacterial Adhesion, General Biochemistry, Genetics and Molecular Biology, Mouse model, Mice, Disease Models, Animal, Crohn's disease, Crohn Disease, Immunology and Microbiology (miscellaneous), Escherichia coli, Humans, Animals, CEACAM6, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Escherichia coli Infections, AIEC
Abstract: Adherent-invasive Escherichia coli (AIEC) were investigated for their involvement in the induction/chronicity of intestinal inflammation in Crohn's disease (CD). AIEC gut establishment is favoured by overexpression of the glycoprotein CEACAM6 in the ileal epithelium. We generated a transgenic mouse model, named ‘Vill-hCC6’, in which the human CEACAM6 gene was under the control of the villin promoter, conditioning expression in the small intestine. We demonstrated that CEACAM6 is strongly expressed in the small intestine mucosa and is correlated with numerous glycosylations displayed at the brush border of enterocytes. Ex vivo, the AIEC–enterocyte interaction was enhanced by CEACAM6 expression and necessitated the presence of the bacterial adhesive factor FimH. Finally, AIEC bacteria preferentially persisted in a FimH-dependent manner in the ileal mucosa of Vill-hCC6 mice compared to wild-type mice. This preclinical model opens new perspectives in the mechanistic study of the AIEC pathobiont and represents a valuable tool to evaluate the efficacy of new strategies to eliminate AIEC implanted in the ileal mucosa, such as phages, inhibitory and/or anti-virulence molecules, or CRISPR-based strategies targeting virulence or fitness factors of AIEC bacteria.
Published: 2022

36. The Plasma Oxylipin Signature Provides a Deep Phenotyping of Metabolic Syndrome Complementary to the Clinical Criteria

Author: Céline Dalle, Jérémy Tournayre, Malwina Mainka, Alicja Basiak-Rasała, Mélanie Pétéra, Sophie Lefèvre-Arbogast, Jessica Dalloux-Chioccioli, Mélanie Deschasaux-Tanguy, Lucie Lécuyer, Emmanuelle Kesse-Guyot, Léopold K. Fezeu, Serge Hercberg, Pilar Galan, Cécilia Samieri, Katarzyna Zatońska, Philip C. Calder, Mads Fiil Hjorth, Arne Astrup, André Mazur, Justine Bertrand-Michel, Nils Helge Schebb, Andrzej Szuba, Mathilde Touvier, John W. Newman, Cécile Gladine, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), University of Wuppertal, Wrocław Medical University, Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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)-Université Toulouse III - Paul Sabatier (UT3), 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 des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Hospital Southampton NHS Foundation Trust, University of Southampton, Novo Nordisk Inc, NOVO NORDISK PARK, University of California [Davis] (UC Davis), University of California (UC), and Western Human Nutrition Research Center
Subjects: metabolic phenotyping, oxylipins, lipid mediators, Catalysis, metabolic syndrome, Inorganic Chemistry, Clinical Research, Genetics, Humans, 2.1 Biological and endogenous factors, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, Aetiology, Molecular Biology, Spectroscopy, Nutrition, Metabolic Syndrome, Chemical Physics, Organic Chemistry, lipidomics, General Medicine, Computer Science Applications, Good Health and Well Being, Cardiovascular Diseases, Case-Control Studies, Other Biological Sciences, Other Chemical Sciences, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Oxylipins are a superfamily of lipid mediators regulating many cardiometabolic functions. Plasma oxylipin signature could provide a new clinical tool to enhance the phenotyping of MetS pathophysiology. A high-throughput validated mass spectrometry method, allowing for the quantitative profiling of over 130 oxylipins, was applied to identify and validate the oxylipin signature of MetS in two independent nested case/control studies involving 476 participants. We identified an oxylipin signature of MetS (coined OxyScore), including 23 oxylipins and having high performances in classification and replicability (cross-validated AUCROC of 89%, 95% CI: 85–93% and 78%, 95% CI: 72–85% in the Discovery and Replication studies, respectively). Correlation analysis and comparison with a classification model incorporating the MetS criteria showed that the oxylipin signature brings consistent and complementary information to the clinical criteria. Being linked with the regulation of various biological processes, the candidate oxylipins provide an integrative phenotyping of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways. This may help identify patients at higher risk of cardiometabolic diseases. The oxylipin signature of patients with metabolic syndrome enhances MetS phenotyping and may ultimately help to better stratify the risk of cardiometabolic diseases.
Published: 2022

37. The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization

Author: Landry L. Tsoumtsa Meda, Luce Landraud, Serena Petracchini, Stéphane Descorps-Declere, Emeline Perthame, Marie-Anne Nahori, Laura Ramirez Finn, Molly A. Ingersoll, Rafael Patiño-Navarrete, Philippe Glaser, Richard Bonnet, Olivier Dussurget, Erick Denamur, Amel Mettouchi, Emmanuel Lemichez, Vougny, Marie-Christine, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Identification de biomarqueurs sanguins prédictifs des infections uriniaires récidivantes et développement d'immunothérapies préventives personnalisées - - PredictUTI2017 - ANR-17-CE17-0014 - AAPG2017 - VALID, Colonisation des tissus et resevoirs infectieux des ExPEC induits par CNF1, nouvelle voie thérapeutique - - ExPECtation2021 - ANR-21-CE15-0006 - AAPG2021 - VALID, Toxines bactériennes - Bacterial Toxins, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Inflammation et immunité des muqueuses - Mucosal Inflammation and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Écologie et Évolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Yersinia, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Fondation ARC [PJA 20191209650], Ligue Nationale contre le Cancer Subvention de Recherche Scientifique [RS20/75-63], Fondation pour la Recherche Médicale (Equipe FRM 2016, DEQ20161136698)., We thank François-Xavier WEILL for fruitful discussions. The plasmids pKOBEG and p3xFlag-CmR CNF1 wildtype were kindly provided by Jean-Marc GHIGO and Petra DERSCH, respectively., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-17-CE17-0014,PredictUTI,Identification de biomarqueurs sanguins prédictifs des infections uriniaires récidivantes et développement d'immunothérapies préventives personnalisées(2017), and ANR-21-CE15-0006,ExPECtation,Colonisation des tissus et resevoirs infectieux des ExPEC induits par CNF1, nouvelle voie thérapeutique(2021)
Subjects: rho GTP-Binding Proteins, Microbiology (medical), ST131, [SDV.IMM] Life Sciences [q-bio]/Immunology, Virulence Factors, UTI, Bacterial Toxins, MESH: beta-Lactamases, Microbiology, beta-Lactamases, MESH: Gastrointestinal Microbiome, Drug Resistance, Multiple, Bacterial, MESH: Anti-Bacterial Agents, Escherichia coli, Humans, Escherichia coli Infections, MESH: Escherichia coli Infections, MESH: Virulence Factors, ExPEC, MESH: Humans, MESH: Escherichia coli, Escherichia coli Proteins, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Drug Resistance, Multiple, Bacterial, colonization, MESH: rho GTP-Binding Proteins, CNF1, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Anti-Bacterial Agents, Gastrointestinal Microbiome, rho GTPases, Infectious Diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, gastrointestinal tract
Abstract: Epidemiological projections point to acquisition of ever-expanding multidrug resistance (MDR) byiEscherichia coli/i, a commensal of the digestive tract and a source of urinary tract pathogens. Bioinformatics analyses of a large collection ofiE. coli/igenomes from EnteroBase, enriched in clinical isolates of worldwide origins, suggest the Cytotoxic Necrotizing Factor 1 (CNF1)-toxin encoding gene,icnf1/i, is preferentially distributed in four common sequence types (ST) encompassing the pandemiciE. coli/iMDR lineage ST131. This lineage is responsible for a majority of extraintestinal infections that escape first-line antibiotic treatment, with known enhanced capacities to colonize the gastrointestinal tract. Statistical projections based on this dataset point to a global expansion oficnf1/i-positive multidrug-resistant ST131 strains from subcladeiH/i30Rx/C2, accounting for a rising prevalence oficnf1/i-positive strains in ST131. Despite the absence of phylogeographical signals,icnf1/i-positive isolates segregated into clusters in the ST131-iH/i30Rx/C2 phylogeny, sharing a similar profile of virulence factors and the sameicnf1/iallele. The suggested dominant expansion oficnf1/i-positive strains in ST131-iH/i30Rx/C2 led us to uncover the competitive advantage conferred byicnf1/ifor gut colonization to the clinical strain EC131GY ST131-iH/i30Rx/C2 versusicnf1/i-deleted isogenic strain. Complementation experiments showed that colon tissue invasion was compromised in the absence of deamidase activity on Rho GTPases by CNF1. Hence, gut colonization factor function oficnf1/iwas confirmed for another clinical strain ST131-iH/i30Rx/C2. In addition, functional analysis of theicnf1/i-positive clinical strain EC131GY ST131-iH/i30Rx/C2 and aicnf1/i-deleted isogenic strain showed no detectable impact of the CNF1 gene on bacterial fitness and inflammation during the acute phase of bladder monoinfection. Together these data argue for an absence of role of CNF1 in virulence during UTI, while enhancing gut colonization capacities of ST131-iH/i30Rx/C2 and suggested expansion oficnf1/i-positive MDR isolates in subclade ST131-iH/i30Rx/C2.
Published: 2022

38. Exposure to polyethylene microplastics alters immature gut microbiome in an infant in vitro gut model

Author: Elora Fournier, Jeremy Ratel, Sylvain Denis, Mathilde Leveque, Philippe Ruiz, Carine Mazal, Frederic Amiard, Mathieu Edely, Valerie Bezirard, Eric Gaultier, Bruno Lamas, Eric Houdeau, Erwan Engel, Fabienne Lagarde, Lucie Etienne-Mesmin, Muriel Mercier-Bonin, Stéphanie Blanquet-Diot, Université Clermont Auvergne (UCA), Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Qualité des Produits Animaux (QuaPA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), 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)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Molécules et Matériaux du Mans (IMMM), Le Mans Université (UM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), ANR-21-CE34-0028,PLASTOX,Toxicité pour l'homme de micro- et nanoplastiques ingérés, en combinaison avec des polluants environnementaux métalliques(2021), and ANR-19-MRS2-0011,HuPlastiX,Dialogue entre la santé humaine et la 'sphère plastique'(2019)
Subjects: Environmental Engineering, Health, Toxicology and Mutagenesis, Microplastics, In vitro gut models, Infant, Cellular models, Gut microbiota, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Pollution, Gastrointestinal Microbiome, Polyethylene, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Environmental Chemistry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, Waste Management and Disposal, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Plastics, Ecosystem
Abstract: International audience; Infants are characterized by an immaturity of the gut ecosystem and a high exposure to microplastics (MPs) through diet, dust and suckling. However, the bidirectional interactions between MPs and the immature infant intestinal microbiota remain unknown. Our study aims to investigate the impact of chronic exposure to polyethylene (PE) MPs on the gut microbiota and intestinal barrier of infants, using the new Toddler mucosal Artificial Colon coupled with a co-culture of epithelial and mucus-secreting cells. Gut microbiota composition was determined by 16S metabarcoding and microbial activities were evaluated by gas, short chain fatty acid and volatolomics analyses. Gut barrier integrity was assessed via evaluation of intestinal permeability, inflammation and mucus synthesis. Exposure to PE MPs induced gut microbial shifts increasing α-diversity and abundance of potentially harmful pathobionts, such as Dethiosulfovibrionaceae and Enterobacteriaceae. Those changes were associated to butyrate production decrease and major changes in volatile organic compounds profiles. In contrast, no significant impact of PE MPs on the gut barrier, as mediated by microbial metabolites, was reported. For the first time, this study indicates that ingestion of PE MPs can induce perturbations in the gut microbiome of infants. Next step would be to further investigate the potential vector effect of MPs.
Published: 2022

39. Impact of COVID-19 Lockdown on Food Consumption and Behavior in France (COVISTRESS Study)

Author: Pouget, Mélanie, Clinchamps, Maëlys, Lambert, Céline, Pereira, Bruno, Farigon, Nicolas, Gentes, Elodie, Miolanne, Magalie, Picard, Mathilde, Tyrode, Anne, Alligier, Maud, Network, Covistress, Dutheil, Frédéric, Boirie, Yves, Service de Nutrition Clinique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Auvergne de l'Obésité et de ses Risques en Santé (CALORIS), Service Santé Travail Environnement [CHU Clermont-Ferrand], Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-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 Grenoble Alpes (UGA), FCRIN/FORCE Network, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), WittyFit, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Nutrition and Dietetics, SARS-CoV-2, COVID-19, lockdown, eating habits, Feeding Behavior, Communicable Disease Control, [SCCO.PSYC]Cognitive science/Psychology, Humans, Life Style, Pandemics, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: International audience; The COVID-19 pandemic and subsequent lockdowns modified work environments, lifestyles, and food consumption. Eating habits and mood changes in a French population during the first lockdown were examined using an online self-reported questionnaire with REDCap software through the COVISTRESS.ORG website. In 671 French participants, the main changes during lockdown were increased stress levels (64 [23; 86] vs. 3 [0; 18]) and sedentary behavior (7 [4; 9] vs. 5 [3; 8] hours per day), a deterioration in sleep quality (50 [27; 83] vs. 70 [48; 94]) and mood (50 [30; 76] vs. 78 [50; 92]), and less physical activity (2.0 [0.5; 5.0] vs. 3.5 [2.0; 6.0]). Mood was modified, with more anger (56 [39; 76] vs. 31 [16; 50]), more sadness (50 [34; 72] vs. 28 [16; 50]), more agitation (50 [25; 66] vs. 43 [20; 50]), and more boredom (32 [7; 60] vs. 14 [3; 29]). A total of 25% of the participants increased their consumption of alcoholic beverages, 29% their consumption of sugary foods, and 26% their consumption of cocktail snacks. A multiple-correspondence analysis highlights four different profiles according to changes in eating habits, food consumption, lifestyle, and mood. In conclusion, eating habits and lifestyle changes during lockdown periods should be carefully monitored to promote healthy behaviors.
Published: 2022
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40. Half of Postoperative Deaths After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Could be Preventable

Author: Catherine Arvieux, Jean-Jacques Tuech, Bertrand Celerier, Etienne Gayat, Olivier Glehen, Naoual Bakrin, Nicolas Pirro, François Quenet, Williams Tessier, Cecilia Ceribelli, Diane Goéré, Brice Paquette, Isabelle Sourrouille, Marc Pocard, Denis Pezet, Cécile Brigand, Jérémie H. Lefevre, Thomas Courvosier-Clement, Abdelkader Taibi, Frédéric Dumont, Olivia Sgarbura, David Moszkowicz, Guillaume Piessen, Koceila Amroun, Pascale Mariani, Clarisse Eveno, Jean-Baptiste Delhorme, Jean-Marc Guilloit, Charles Sabbagh, Constance Houlzé-Laroye, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Department of Anesthesiology & Critical Care, Hôpital Lariboisière, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Jean Godinot [Reims], Centre Hospitalier Universitaire [Grenoble] (CHU), Maladies et hormones du système nerveux (DHNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital de la Timone [CHU - APHM] (TIMONE), Sorbonne Université (SU), Service de Chirurgie Digestive [CHRU Besançon], Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Curie [Paris], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Hôpital Claude Huriez [Lille], CHU Lille, Université de Bordeaux (UB), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Limoges, 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), Institut du Cancer de Montpellier (ICM), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], CArcinose Péritoine Paris-Technologies (ex-CART) (CAP Paris-Tech (UMR_S_1275)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Gustave Roussy (IGR), Département de chirurgie viscérale [Gustave Roussy], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Postoperative death, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Hyperthermic Intraperitoneal Chemotherapy, cytoreductive surgery, Humans, Medicine, Postoperative Period, Peritoneal Neoplasms, Aged, Retrospective Studies, Cause of death, peritoneal surface malignancies, HIPEC, Performance status, business.industry, Cytoreduction Surgical Procedures, Perioperative, Middle Aged, Prognosis, Surgery, Survival Rate, postoperative mortality, peritoneal metastasis, Peritoneal Cancer Index, Etiology, Female, Root Cause Analysis, Hyperthermic intraperitoneal chemotherapy, France, business, Root cause analysis
Abstract: International audience; Objective: To perform a retrospective root-cause analysis of postoperative death after CRS and HIPEC procedures. Background: The combination of CRS and HIPEC is an effective therapeutic strategy to treat peritoneal surface malignancies, however it is associated with significant postoperative mortality. Methods: All patients treated with a combination of CRS and HIPEC between January 2009 and December 2018 in 22 French centers and died in the hospital, were retrospectively analyzed. Perioperative data of the 101 patients were collected by a local senior surgeon with a sole junior surgeon. Three independent experts investigated the typical root cause of death and provided conclusions on whether postoperative death was preventable (PREV group) or not (NON-PREV group). A typical root cause of preventable postoperative death was classified on a cause-and-effect diagram. Results: Of the 5562 CRS+HIPEC procedures performed, 101 in-hospital deaths (1.8%) were identified, of which a total of 18 patients of 70 years old and above and 20 patients with ASA score of 3. Etiology of peritoneal disease was mainly colorectal. A total of 54 patients (53%) were classified in the PREV group and 47 patients (47%) in the NON-PREV group. The results of the study show that in the PREV group, WHO performance status 1-2 was more frequent and the Median Peritoneal Cancer Index was higher compared with those of the NON-PREV group. The cause of death in the PREV group was classified as: (i) preoperatively for debatable indication (59%), (ii) intraoperatively (30%) and (iii) postoperatively in 17 patients (31%). A multifactorial cause of death was found in 11 patients (20%). Conclusion: More than half of the postoperative deaths after combined CRS and HIPEC may be preventable, mainly by following guidelines regarding preoperative selection of the patients and adequate intraoperative decisions.
Published: 2021

41. France’s 2020 Report Card on Physical Activity and Sedentary Behaviors in Children and Youth: Results and Progression

Author: David Thivel, Salomé Aubert, Benjamin Larras, Julien Bois, Olivier Rey, Lena Lhuisset, Martine Duclos, Maxime Luiggi, Nicole Fearnbach, Alicia Fillon, Pauline Genin, Charlotte Verdot, Jeremy Vanhelst, Observatoire national de l’activité physique et de la sédentarité (ONAPS), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), French Institute of Sport (INSEP), Laboratory Sport, Expertise and Performance (EA7370) (SEP (EA7370)), Institut national du sport, de l'expertise et de la performance (INSEP), Children's Hospital of Eastern Ontario Research Institute, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Mouvement, Équilibre, Performance, Santé (MEPS), Université de Pau et des Pays de l'Adour (UPPA), Pennington Biomedical Research Center, Louisiana State University (LSU), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Université de Clermont-Ferrand, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, French Institute of Sport (INSEP), Research Department, Laboratory Sport, Expertise and Performance (EA7370) (SEP (EA7370)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université de Lille, LillOA, Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Inserm, CHU Lille, Observatoire national de l’activité physique et de la sédentarité [ONAPS], Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Lille Inflammation Research International Center - U 995 [LIRIC], Institut national du sport, de l'expertise et de la performance [INSEP], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité [CRESS (U1153 / UMR_A_1125 / UMR_S_1153)], Institut des Sciences du Mouvement Etienne Jules Marey [ISM], Université de Pau et des Pays de l'Adour [UPPA], Mouvement, Équilibre, Performance, Santé [MEPS], and Southern University and A&M College [Baton Rouge, Louisiana]
Subjects: Gerontology, Adolescent, Coronavirus disease 2019 (COVID-19), [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Physical fitness, Physical activity, Health Promotion, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, active transportation, Orthopedics and Sports Medicine, adolescents, 030212 general & internal medicine, Child, Grading (education), Exercise, Built environment, Active play, [SHS.SPORT]Humanities and Social Sciences/Sport, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Government, business.industry, Health Policy, 4. Education, COVID-19, physical activity promotion, 030229 sport sciences, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Sedentary Behavior, business, Psychology, Report card
Abstract: Background: There is an alarming and constant worldwide progression of physical inactivity and sedentary behaviors in children and adolescents. The present paper summarizes findings from France’s 2020 Report Card on physical activity for children and youth, comparing its results to its 2 previous editions (2016 and 2018). Methods: France’s 2020 Report Card follows the standardized methodology established by the Active Healthy Kids Global Matrix, grading 10 common physical activity indicators using the best available evidence. The grades were informed by national surveys, peer-reviewed literature, government and nongovernment reports, and online information. Results: The expert panel awarded the following grades: Overall Physical Activity: D; Organized Sport Participation and Physical Activity: C−; Active Play: INC; Active Transportation: C−; Sedentary Behaviors: D−; Family and Peers: D−; Physical Fitness: D; School: B−; Community and the Built Environment: F; Government: C. Conclusions: This 2020 edition of France’s Report Card again highlights the alarming levels of physical activity and sedentary behaviors among French children and adolescents, calling for the development of effective national action. It also draws attention to the particular deleterious effects of the COVID-19 confinement on youth’s movement behaviors, which significantly worsened the situation.
Published: 2021

42. Sarcopenia in patients after an episode of acute decompensated heart failure: An underdiagnosed problem with serious impact

Author: Stefan D. Anker, Ruddy Richard, Guillaume Clerfond, Yves Boirie, Pierre-Louis Tartière, Clément Riocreux, Patrick Rossignol, Bruno Pereira, Géraud Souteyrand, Nicolas Combaret, Marie Blanquet, Marie-Claire D'Agrosa Boiteux, Pascal Motreff, Aurélien Mulliez, Pelle Stolt, Frédéric Jean, Romain Eschalier, Grégoire Massoullié, CHU Clermont-Ferrand, SIGMA Clermont (SIGMA Clermont), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, CH Mauriac, Biostatistics Unit (Department of Clinical Research and Innovation), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Clinique Médicale Cardio-Pneumologie de Durtol, Maglia Rotta, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), ROSSI, Sabine, Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Sarcopenia, Longitudinal study, medicine.medical_specialty, Acute decompensated heart failure, Decompensated chronic heart failure, 030209 endocrinology & metabolism, Decompensation, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Activities of Daily Living, Prevalence, Humans, Medicine, In patient, Longitudinal Studies, Prospective Studies, Aged, Aged, 80 and over, Heart Failure, 030109 nutrition & dietetics, Nutrition and Dietetics, Hand Strength, business.industry, musculoskeletal system, medicine.disease, Chronic heart failure, 3. Good health, Hospitalization, body regions, Clinical trial, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cross-Sectional Studies, Dysmobility, Cohort, Female, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, human activities
Abstract: International audience; Background & aims: Sarcopenia is a multifactorial syndrome resulting in a decrease in both muscle mass and function. Little is known about the prevalence and prognostic impact of sarcopenia in patients with acutely decompensated chronic heart failure (ADHF). We aimed to evaluate the prevalence (main endpoint) and impact of sarcopenia on ADHF patients.Methods: 140 ADHF patients were enrolled between November 2014 and September 2018 in a multi-center prospective longitudinal study. A similar, independent multi-departmental cross-sectional study in 165 ADHF patients was used for external validation of prevalence data. All subjects were assessed on the European Working Group on Sarcopenia criteria.Results: Ninety-one patients (65%) had sarcopenia (vs. 53.6% in the external replication regional cohort). Patients with sarcopenia were older and more likely to have eGFR
Published: 2021

43. Hypercoagulability in critically ill patients with COVID 19, an observational prospective study

Author: Laure Calvet, François Thouy, Olivier Mascle, Anne-Françoise Sapin, Kévin Grapin, Jean Mathias Liteaudon, Bertrand Evrard, Benjamin Bonnet, Mireille Adda, Bertrand Souweine, Claire Dupuis, Service de Médecine Intensive et Réanimation [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratoire Microorganismes : Génome et Environnement (LMGE), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)
Subjects: Multidisciplinary, Critical Illness, Thromboembolism, Humans, COVID-19, Thrombophilia, Prospective Studies, Blood Coagulation Disorders, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Hemostatics, Thrombelastography
Abstract: Objective COVID 19 is often associated with hypercoagulability and thromboembolic (TE) events. The aim of this study was to assess the characteristics of hypercoagulability and its relationship with new-onset TE events and the composite outcome of need for intubation and/or death in intensive care unit (ICU) patients admitted for COVID. Design Prospective observational study. Setting Monocentric, intensive care, University Hospital of Clermont Ferrand, France. Patients Patients admitted to intensive care from January 2020 to May 2021 for COVID-19 pneumonia. Interventions Standard hemostatic tests and rotational thromboelastometry (ROTEM) were performed on admission and on day 4. Hypercoagulability was defined by at least one of the following criteria: D-dimers > 3000 μg/dL, fibrinogen > 8 g/L, EXTEM CFT below the normal range, EXTEM A5, MCF, Li 60 above the normal range, and EXTEM G-score ((5000 x MCF) / (100-MCF)) ≥ 11 dyne/cm2. Measurements and main results Of the 133 patients included, 17 (12.7%) developed new-onset TE events, and 59 (44.3%) required intubation and/or died in the ICU. ROTEM was performed in 133 patients on day 1 and in 67 on day 4. Hypercoagulability was present on day 1 in 115 (86.4%) patients. None of the hypercoagulability indices were associated with subsequent new-onset TE events on days 1 and 4 nor with the need for intubation and/or ICU death. Hyperfibrinogenemia > 8g/dL, higher D-dimers and higher EXTEM Li 60 on day 4 were predictive of need for intubation and/or of ICU death. Conclusions Our study confirmed that most COVID-19 ICU patients have hypercoagulability on admission and almost all on day 4. Hyperfibrinogenemia or fibrinolysis shutdown on day 4 were associated with unfavorable outcome.
Published: 2022

44. Costing the economic burden of prolonged sedentary behaviours in France

Author: Antoine Noël Racine, Irène Margaritis, Martine Duclos, François Carré, Anne Vuillemin, Christèle Gautier, CREPS Auvergne Rhône Alpes [Vichy], Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), 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)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA), Ministère chargé des sports, the French Ministry of Sport, and GUITTON, SOPHIE
Subjects: MESH: Humans, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, MESH: Health Care Costs, Financial Stress, Health Care Costs, MESH: Cost of Illness, [SDV] Life Sciences [q-bio], MESH: France, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: Sedentary Behavior, Cost of Illness, Humans, France, MESH: Financial Stress, Sedentary Behavior, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Background There is strong evidence showing that sedentary behaviour time increase the risk to develop several chronic diseases and to premature death. The economic consequences of this risk have never been evaluated in France. The aim of this study was to estimate the economic burden of prolonged sedentary behaviour in France. Methods Based on individual sedentary behaviour time, relative risk to develop cardiovascular disease, colon cancer, breast cancer and all-causes of premature mortality were identified. From relative risk and prevalence of sedentary behaviour time, a population attributable fraction approach was used to estimate the yearly number of cases for each disease. Data from the National Health Insurance were used to calculate the annual average costs per case for each disease. Disease-specific and total healthcare costs attributable to prolonged sedentary behaviour time were calculated. Indirect costs from productivity loss due to morbidity and premature mortality were estimated using a friction cost approach. Results In France, 51 193 premature deaths/year appear related to a prolonged daily sedentary behaviour time. Each year prolonged sedentary behaviour cost 494 million € for the national health insurance. Yearly productivity loss due to premature mortality attributable to prolonged sedentary behaviour cost 507 million € and yearly productivity loss due to morbidity cost between 43 and 147 million €. Conclusion Significant saving and many deaths could be avoided by reducing prolonged sedentary behaviour prevalence in France. To address this issue, strong responses should be implemented to tackle sedentary behaviour, complementary to physical activity promotion.
Published: 2022

45. Lacticaseibacillus rhamnosus Lcr35 Stimulates Epithelial Vaginal Defenses upon Gardnerella vaginalis Infection

Author: Sylvie Miquel, Julien Verlaguet, Sophie Garcin, Thomas Bertran, Bertrand Evrard, Christiane Forestier, Marjolaine Vareille-Delarbre, Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and CHU Clermont-Ferrand
Subjects: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions, beta-Defensins, Lacticaseibacillus rhamnosus, Immunology, Interleukin-8, vaginosis, Vaginosis, Bacterial, Microbiology, Gardnerella vaginalis, epithelial cells, Anti-Bacterial Agents, Lactobacillus, antimicrobial peptides, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Vagina, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Humans, Parasitology, Female, Secretory Leukocyte Peptidase Inhibitor, dendritic cells, Chemokines
Abstract: International audience; Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria, such as Gardnerella vaginalis, and low levels of "healthy" lactobacilli leads to bacterial vaginosis (BV), usually associated with a low-grade inflammatory process. Despite appropriate antibiotic treatment, G. vaginalis-associated BV is characterized by significant recurrence. The use of probiotics could be an interesting alternative therapy due to their ability to rebalance vaginal microbiota. In this study, we investigated the effects of a wellcharacterized probiotic strain, Lacticaseibadllus rhamnosus Lcr35, on epithelial vaginal and dendritic cell (DC) immune responses after G. vaginalis infection. In an in vitro coculture model with human monocyte-derived dendritic cells and a vaginal epithelial cell NEC) monolayer, the Lcr35 strain induced DC activation, as evidenced by the induction of maturation and synthesis of interleukin-8 (IL-8) and CCL-20 chemokines upon apical challenge of the VECs by G. vaginas. Analysis of the vaginal epithelial response showed that the presence of Lcr35 significantly increased the production of the proinflammatory cytokines IL-8 and IL-1 beta and human beta-defensin 2 (HBD-2), whereas the concentration of secretory leukocyte protease inhibitor (SLPI) was decreased in G. vagina/is-infected vaginal epithelial cells. Treatment with recombinant SLPI was associated with upregulation of Lcr35-stimulated IL-8 and HBD-2 production. These results suggest that inhibition of SLPI by Lcr35 in vaginal epithelial cells contributes to the host defense response against G. vaginalis infection.
Published: 2022

46. Mechanisms of myostatin and activin A accumulation in chronic kidney disease

Author: Stanislas Bataille, Laetitia Dou, Marc Bartoli, Marion Sallée, Julien Aniort, Borhane Ferkak, Rania Chermiti, Nathalie McKay, Nathalie Da Silva, Stéphane Burtey, Stéphane Poitevin, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre d'enseignement Cnam Paris (CNAM Paris), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Phocean Nephrology Institute, Clinique Bouchard, ELSAN, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Clermont-Ferrand, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Service d'Evaluation Médicale APHM Marseille
Subjects: Mammals, Transplantation, muscle, [SDV]Life Sciences [q-bio], musculoskeletal system, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Activins, sarcopenia, Mice, Nephrology, myostatin, Animals, Humans, activin A, Renal Insufficiency, Chronic, Muscle, Skeletal, indoxyl sulfate, Indican, chronic kidney disease
Abstract: Background Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mammalian target of rapamycin pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is unclear if there is increased production or decreased renal clearance. Methods We measured myostatin and activin A concentrations in 232 CKD patients and studied their correlation with estimated glomerular filtration rate (eGFR). We analyzed the myostatin gene (MSTN) expression in muscle biopsies of hemodialysis (HD) patients. We then measured circulating myostatin and activin A in plasma and the Mstn and Inhba expression in muscles, kidney, liver and heart of two CKD mice models (adenine and 5/6 nephrectomy models). Finally, we analyzed whether the uremic toxin indoxyl sulfate (IS) increased Mstn expression in mice and cultured muscle cells. Results In patients, myostatin and activin A were inversely correlated with eGFR. MSTN expression was lower in HD patients’ muscles (vastus lateralis) than in controls. In mice with CKD, myostatin and activin A blood concentrations were increased. Mstn was not upregulated in CKD mice tissues. Inha was upregulated in kidney and heart. Exposure to IS did not induce Mstn upregulation in mouse muscles and in cultured myoblasts and myocytes. Conclusion During CKD, myostatin and activin A blood concentrations are increased. Myostatin is not overproduced, suggesting only an impaired renal clearance, but activin A is overproduced in the kidney and heart. We propose to add myostatin and activin A to the list of uremic toxins.
Published: 2022

47. Variability in Skeletal Muscle Protein Synthesis Rates in Critically Ill Patients

Author: Tjäder, Inga, Klaude, Maria, Hssain, Ali Ait, Guillet, Christelle, Nennesmo, Inger, Wernerman, Jan, Rooyackers, Olav, Karolinska University Hospital [Stockholm], Dept. of Internal Medicine - Intensive Care Unit, CHR St. Joseph-Warquignies, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and Karolinska Institutet [Stockholm]
Subjects: Mitochondrial Proteins, protein synthesis, multiple organ failure, Critical Illness, stable isotopes, Humans, Muscle Proteins, Myosins, muscle morphology, Muscle, Skeletal, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Actins
Abstract: International audience; (1) Background: Muscle protein synthesis in critically ill patients is, on average, normal despite dramatic muscle loss, but the variation is much larger than in controls. Here, we evaluate if this variation is due to 1) heterogeneity in synthesis rates, 2) morphological variation or infiltrating cells, or 3) heterogeneity in the synthesis of different protein fractions. (2) Methods: Muscle biopsies were taken from both legs of critically ill patients (n = 17). Mixed and mitochondrial protein synthesis rates and morphologies were evaluated in both legs. Synthesis rates of myosin and actin were determined in combined biopsies and compared with controls. (3) Results: Muscle protein synthesis rates had a large variability in the patients (1.4–10.8%/day). No differences in mixed and mitochondrial protein synthesis rates between both legs were observed. A microscopic examination revealed no morphological differences between the two legs or any infiltrating inflammatory cells. The synthesis rates for myosin were lower and for actin they were higher in the muscles of critically ill patients, compared with the controls. (4) Conclusions: The large variation in muscle protein synthesis rates in critically ill patients is not the result of heterogeneity in synthesis rates, nor due to infiltrating cells. There are differences in the synthesis rates of different proteins, but these do not explain the larger variations.
Published: 2022

48. Efficacy of donepezil for the treatment of oxaliplatin-induced peripheral neuropathy: DONEPEZOX, a protocol of a proof of concept, randomised, triple-blinded and multicentre trial

Author: Nicolas Kerckhove, David Tougeron, Côme Lepage, Denis Pezet, Karine Le Malicot, Manon Pelkowski, Bruno Pereira, David Balayssac, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, 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), Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Fédération Francophone de Cancérologie Digestive (FFCD), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, French Ministry of Health, National Institute of Cancer ('Institut National du Cancer (INCa) : Programme Hospitalier de Recherche Clinique Cancer', {20-082 PHRC-K], and Molé, Christine
Subjects: Chemotherapy-induced peripheral neuropathy, Cancer Research, Peripheral Nervous System Diseases, Pain, [SDV.CAN]Life Sciences [q-bio]/Cancer, Anticholinesterase, Oxaliplatin, Clinical Trials, Phase III as Topic, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Study protocol, Quality of Life, Genetics, Humans, Multicenter Studies as Topic, Donepezil, Randomized Controlled Trials as Topic
Abstract: Background The use of oxaliplatin in digestive tract cancers could induce severe peripheral neuropathy (OIPN) decreasing the quality of life of patients and survivors. There is currently, no univocal treatment for these peripheral neuropathies. Donepezil, a reversible inhibitor of cholinesterase, used to treat Alzheimer’s disease and dementia, is reported to have a good safety profile in humans, and preclinical data have provided initial evidence of its effectiveness in diminishing neuropathic symptoms and related comorbidities in OIPN animal models. Methods The DONEPEZOX trial will be a proof-of-concept, randomised, triple-blinded, and multicentre study. It will be the first clinical trial evaluating the efficacy and safety of donepezil for the management of OIPN. Adult cancer survivors with OIPN that report sensory neuropathy according to QLQ-CIPN20 sensory score (equivalence of a grade ≥ 2), at least 6 months after the end of an oxaliplatin-based chemotherapy will be included. Eighty patients will be randomly assigned to receive either donepezil or placebo over 16 weeks of treatment. The primary endpoint will be the rate of responders (neuropathic grade decreases according to the QLQ-CIPN20 sensory score) in the donepezil arm. The severity of OIPN will be assessed by the QLQ-CIPN20 sensory scale before and after 16 weeks of treatment. The comparison versus the placebo arm will be a secondary objective. The other secondary endpoints will be tolerance to donepezil, the severity and features of OIPN in each arm before and after treatment, related-comorbidities and quality of life. Fleming’s one-stage design will be used for sample size estimation. This design yields a type I error rate of 0.0417 and power of 91% for a responder rate of at least 30% in donepezil arm. A total of 80 randomized patients is planned. Discussion This study will allow, in the case of positive results, to initiate a phase 3 randomized and placebo-controlled (primary endpoint) clinical study to assess the therapeutic interest of donepezil to treat OIPN. Trial registration NCT05254639, clincialtrials.gov, Registered 24 February 2022.
Published: 2022

49. Digital intervention promoting physical activity among obese people (DIPPAO) randomised controlled trial: study protocol

Author: Alexandre Mazéas, Aïna Chalabaev, Marine Blond, Bruno Pereira, Martine Duclos, Université Grenoble Alpes (UGA), Département sciences pour l'action, les transitions, les territoires (ACT), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Kiplin, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and Dept Sport Med and Funct Explorat
Subjects: Diabetes Mellitus, Type 2, Cost-Benefit Analysis, Humans, General Medicine, Obesity, Sedentary Behavior, Exercise, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Randomized Controlled Trials as Topic
Abstract: IntroductionPhysical inactivity and excessive sedentary behaviours are major preventable causes in both the development and the treatment of obesity and type 2 diabetes mellitus (T2DM). Nevertheless, current programmes struggle to engage and sustain physical activity (PA) of patients over long periods of time. To overcome these limitations, the Digital Intervention Promoting Physical Activity among Obese people randomised controlled trial (RCT) aims to evaluate the effectiveness of a group-based digital intervention grounded on gamification strategies, enhanced by social features and informed by the tenets of the self-determination theory and the social identity approach.Methods and analysisThis trial is a two-arm parallel RCT testing the effectiveness of the Kiplin digital intervention on obese and patients with T2DM in comparison to the usual supervised PA programme of the University Hospital of Clermont-Ferrand, France. A total of 50 patients will be randomised to one of the two interventions and will follow a 3-month programme with a 6-month follow-up postintervention. The primary outcome of the study is the daily step count change between the baseline assessment and the end of the intervention. Accelerometer data, self-reported PA, body composition and physical capacities will also be evaluated. To advance our understanding of complex interventions like gamified and group-based ones, we will explore several psychological mediators relative to motivation, enjoyment, in-group identification or perceived weight stigma. Finally, to assess a potential superior economic efficiency compared with the current treatment, we will conduct a cost–utility analysis between the two conditions. A mixed-model approach will be used to analyse the change in outcomes over time.Ethics and disseminationThe research protocol has been reviewed and approved by the Local Human Protection Committee (CPP Ile de France XI, No 21 004-65219). Results will inform the Kiplin app development, be published in scientific journals and disseminated in international conferences.Trial registration numberNCT04887077.
Published: 2022

50. Major gastrointestinal bleeding in patients receiving anticoagulant therapy for venous thromboembolism

Author: Judith Catella, Laurent Bertoletti, Farès Moustafa, José Antonio Nieto, Reina Valle, José María Pedrajas, Aurora Villalobos, Isabelle Quere, Gabrielle Sarlon-Bartoli, Manuel Monreal, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Hospital Virgen De La Luz, Hospital Sierrallana, Partenaires INRAE, Hospital Clínico San Carlos [Madrid, Spain], Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Timone [CHU - APHM] (TIMONE), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), and Universidad Católica San Antonio de Murcia (UCAM)
Subjects: Male, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Anticoagulants, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Registries, Gastrointestinal Hemorrhage, Pulmonary Embolism, Gastrointestinal bleeding, Aged, Venous thromboembolism
Abstract: International audience; Introduction: The gastrointestinal (GI) tract is a frequent site of bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE). At-risk patients have not been consistently identified yet. Methods: We used the RIETE registry to assess the clinical characteristics of patients developing major GI bleeding during the course of anticoagulation. Then, we built a predictive score based on multivariable analysis, aiming to identify patients at increased risk for major GI bleeding. Results: We included 87,431 patients with acute VTE. During the course of anticoagulation, 778 (0.89%) suffered major GI bleeding, 815 (0.93%) non-major GI bleeding and 1462 (1.67%) had major bleeding outside the GI tract. During the first 30 days after major GI bleeding, 7.6% of patients re-bled, 3.9% had VTE recurrences and 33% died. On multivariable analysis, male sex, age >= 70 years, initial VTE presentation as pulmonary embolism, active cancer, prior VTE, recent major bleeding in the GI tract, esophageal varicosities, anemia, abnormal prothrombin time, renal insufficiency and use of corticosteroids were associated to an increased risk for major GI bleeding. Using the predictive score, 39,591 patients (45%) were at low risk; 36,602 (42%) at intermediate-risk; 9315 (11%) at high-risk; and 1923 (2.2%) at very high risk. Their rates of major GI bleeding were: 0.21%, 0.96%, 2.41% and 6.08%, respectively. The c-statistics was 0.771 (95%CI. 0.755-0.786). Conclusions: We have developed a score which has the potential to identify patients at increased risk for GI bleeding, but needs to be externally validated."
Published: 2022

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