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1. Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice

Author

Eva Conde, Romain Bertrand, Bianca Balbino, Jonathan Bonnefoy, Julien Stackowicz, Noémie Caillot, Fabien Colaone, Samir Hamdi, Raïssa Houmadi, Alexia Loste, Jasper B. J. Kamphuis, François Huetz, Laurent Guilleminault, Nicolas Gaudenzio, Aurélie Mougel, David Hardy, John N. Snouwaert, Beverly H. Koller, Vincent Serra, Pierre Bruhns, Géraldine Grouard-Vogel, and Laurent L. Reber

Subjects
Science
Abstract

Asthma is caused by hyperreactivity to benign antigens, with humoral immunity orchestrated by interleukin-4 (IL-4) and IL-13 being the key etiological factor. Here the authors show, in humanized mouse models, that dual vaccination against IL-4 and IL-13 induces their durable suppression ameliorate experimental asthma, and to hint clinical translation.

Published
2021
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2. Food-grade TiO2 is trapped by intestinal mucus in vitro but does not impair mucin O-glycosylation and short-chain fatty acid synthesis in vivo: implications for gut barrier protection

Author

Pauline Talbot, Joanna M. Radziwill-Bienkowska, Jasper B. J. Kamphuis, Karine Steenkeste, Sarah Bettini, Véronique Robert, Marie-Louise Noordine, Camille Mayeur, Eric Gaultier, Philippe Langella, Catherine Robbe-Masselot, Eric Houdeau, Muriel Thomas, and Muriel Mercier-Bonin

Subjects
Food-grade TiO2, Gut barrier, Mucin O-glycans, Mucus, Short-chain fatty acids, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
Abstract

Abstract Background Titanium dioxide (TiO2) particles are commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, the risk of gut barrier disruption is an increasing concern because of the presence of a nano-sized fraction. Food-grade E171 may interact with mucus, a gut barrier protagonist still poorly explored in food nanotoxicology. To test this hypothesis, a comprehensive approach was performed to evaluate in vitro and in vivo interactions between TiO2 and intestinal mucus, by comparing food-grade E171 with NM-105 (Aeroxyde P25) OECD reference nanomaterial. Results We tested E171-trapping properties of mucus in vitro using HT29-MTX intestinal epithelial cells. Time-lapse confocal laser scanning microscopy was performed without labeling to avoid modification of the particle surface. Near-UV irradiation of E171 TiO2 particles at 364 nm resulted in fluorescence emission in the visible range, with a maximum at 510 nm. The penetration of E171 TiO2 into the mucoid area of HT29-MTX cells was visualized in situ. One hour after exposure, TiO2 particles accumulated inside “patchy” regions 20 µm above the substratum. The structure of mucus produced by HT29-MTX cells was characterized by MUC5AC immunofluorescence staining. The mucus layer was thin and organized into regular “islands” located approximately 20 µm above the substratum. The region-specific trapping of food-grade TiO2 particles was attributed to this mucus patchy structure. We compared TiO2-mediated effects in vivo in rats after acute or sub-chronic oral daily administration of food-grade E171 and NM-105 at relevant exposure levels for humans. Cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged, irrespective of treatment. Conclusions Food-grade TiO2 is trapped by intestinal mucus in vitro but does not affect mucin O-glycosylation and short-chain fatty acid synthesis in vivo, suggesting the absence of a mucus barrier impairment under “healthy gut” conditions.

Published
2018
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3. Toxicity of Food-Grade TiO2 to Commensal Intestinal and Transient Food-Borne Bacteria: New Insights Using Nano-SIMS and Synchrotron UV Fluorescence Imaging

Author

Joanna M. Radziwill-Bienkowska, Pauline Talbot, Jasper B. J. Kamphuis, Véronique Robert, Christel Cartier, Isabelle Fourquaux, Esther Lentzen, Jean-Nicolas Audinot, Frédéric Jamme, Matthieu Réfrégiers, Jacek K. Bardowski, Philippe Langella, Magdalena Kowalczyk, Eric Houdeau, Muriel Thomas, and Muriel Mercier-Bonin

Subjects
food-grade TiO2, bacterial toxicity, intestinal bacteria, food-borne bacteria, cellular and subcellular bioimaging, Microbiology, QR1-502
Abstract

Titanium dioxide (TiO2) is commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, a risk of intestinal barrier disruption, including dysbiosis of the gut microbiota, is increasingly suspected because of the presence of a nano-sized fraction in this additive. We hypothesized that food-grade E171 and Aeroxyde P25 (identical to the NM-105 OECD reference nanomaterial in the European Union Joint Research Centre) interact with both commensal intestinal bacteria and transient food-borne bacteria under non-UV-irradiated conditions. Based on differences in their physicochemical properties, we expect a difference in their respective effects. To test these hypotheses, we chose a panel of eight Gram-positive/Gram-negative bacterial strains, isolated from different biotopes and belonging to the species Escherichia coli, Lactobacillus rhamnosus, Lactococcus lactis (subsp. lactis and cremoris), Streptococcus thermophilus, and Lactobacillus sakei. Bacterial cells were exposed to food-grade E171 vs. P25 in vitro and the interactions were explored with innovative (nano)imaging methods. The ability of bacteria to trap TiO2 was demonstrated using synchrotron UV fluorescence imaging with single cell resolution. Subsequent alterations in the growth profiles were shown, notably for the transient food-borne L. lactis and the commensal intestinal E. coli in contact with food-grade TiO2. However, for both species, the reduction in cell cultivability remained moderate, and the morphological and ultrastructural damages, observed with electron microscopy, were restricted to a small number of cells. E. coli exposed to food-grade TiO2 showed some internalization of TiO2 (7% of cells), observed with high-resolution nano-secondary ion mass spectrometry (Nano-SIMS) chemical imaging. Taken together, these data show that E171 may be trapped by commensal and transient food-borne bacteria within the gut. In return, it may induce some physiological alterations in the most sensitive species, with a putative impact on gut microbiota composition and functioning, especially after chronic exposure.

Published
2018
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4. The anti‐FcεRI antibody MAR‐1 depletes basophils and cross‐reacts with myeloid cells through its Fc portion

Author

William P. M. Worrall, Jasper B. J. Kamphuis, Julien Stackowicz, Aurélie Mougel, Emilie Mauré, Cyprien Pecalvel, Sébastien Brûlé, Pierre Bruhns, Laurent Guilleminault, Laurent L. Reber, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Sorbonne Université (SU), Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), ANR-18-CE18-0023,AllergyVACS,Développement d'un vaccin thérapeutique pour les maladies allergiques(2018), and ANR-20-CE15-0026,AsthmAb,Role des IgE humaines et de leur récepteur FceRI dans l'asthme et sa potentialisation par l'obésité(2020)

Subjects
basophil, Leukocyte Count, Receptors, IgE, Immunology, anaphylaxis, Humans, Immunology and Allergy, IgE, Mast Cells, Immunoglobulin E, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cell Degranulation, Basophils
Abstract

International audience; In humans, the high-affinity IgE receptor FcεRI is expressed as a tetramer in mast cells (MCs) and basophils, and as a trimer in additional myeloid cell populations, including monocytes, macrophages, dendritic cells (DCs), and Langerhans cells.1 In mice, the expression profile of FcεRI is more debatable. Some studies report FcεRI+ macrophages and DCs.2 However, recent data indicate that the anti-FcεRI mAb (clone MAR-1) used in all these studies can recognize myeloid cells in an FcεRI-independent manner, and cross-reacts with FcγRI and FcγRIV.3, 4 Since MAR-1 has been extensively used in vivo to assess the role of FcεRI and to deplete basophils,5 the off-target effects of this mAb raise concerns regarding some of the conclusions made in prior studies. We thus decided to assess by which mechanism MAR-1 cross-reacts with FcγRs, and whether this cross-reactivity accounts for some of the functions previously attributed to FcεRI and/or basophils.

Published
2022
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6. Comment on 'Tumor-initiating cells establish an IL-33–TGF-β niche signaling loop to promote cancer progression'

Author

Julien Stackowicz, Aurélie Mougel, Pierre Bruhns, Jinmiao Chen, Eva Conde, William P. M. Worrall, Rebecca Gentek, Jasper B. J. Kamphuis, Nicolas Gaudenzio, Laurent L. Reber, Laurent Guilleminault, Emilie Mauré, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), Sorbonne Université (SU), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], CHU Toulouse [Toulouse], Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), University of Edinburgh, Supported by a fellowship from the Institut National de la Santé et de la Recherche Médicale (INSERM) ATIP-Avenir program (J.B.J.K.), a fellowship from INSERM-Region Occitanie (W.P.M.W.), the European Research Council (ERC)–Seventh Framework Program (ERC-2013-CoG 616050), the Institut Pasteur, and INSERM (P.B.), the Société Française de Dermatologie (SFD), the Société Française d’Allergologie (SFA), the Marie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2016 #749629), the European Research Council (ERC-2018-STG #802041), and the INSERM ATIP-Avenir program (N.G.), a Chancellor’s Fellowship of the University of Edinburgh and a Senior Research Fellowship from the Kennedy Trust for Rheumatology Research (R.G.), and the INSERM ATIP-Avenir program (L.L.R.), European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), European Project: 802041, European Project: 749629,H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility ,H2020-MSCA-IF-2016,NEMESIS(2017), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bruhns, Pierre, Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples - MYELOSHOCK - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616050 - VALID, ERC-2018-STG - 802041 - INCOMING, and Neuron/mast cell interactions in skin diseases - NEMESIS - - H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility 2017-07-01 - 2019-06-30 - 749629 - VALID

Subjects
0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, MESH: Receptors, IgE, Immunoglobulin E, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, Neoplasms, medicine, Humans, Receptor, MESH: Transforming Growth Factor beta, MESH: Humans, Multidisciplinary, biology, Receptors, IgE, Cancer, Transforming growth factor beta, Interleukin-33, medicine.disease, MESH: Interleukin-33* / genetics, MESH: Neoplastic Stem Cells, 3. Good health, [SDV] Life Sciences [q-bio], Interleukin 33, MESH: Neoplasms* / genetics, 030104 developmental biology, Cytokine, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, biology.protein, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, Transforming growth factor
Abstract

Taniguchi et al . (Research Articles, 17 July 2020, p. 269) claim that the cytokine interleukin-33 induces accumulation of tumor-associated macrophages expressing the immunoglobulin E receptor FcεRI. Although these findings hold great therapeutic promise, we provide evidence that the anti-FcεRI antibody used in this study is not specific for FcεRI on macrophages, which raises concerns about the validity of some of the conclusions.

Published
2021
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7. Mucus organisation is shaped by colonic content; a new view

Author

Vassilia Theodorou, Helene Eutamene, Jasper B. J. Kamphuis, Muriel Mercier-Bonin, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), European Project: 607652, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Eutamene, Hélène, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Colon, [SDV]Life Sciences [q-bio], Science, toxicologie alimentaire, Article, mucus intestinal, Feces, 03 medical and health sciences, Spatio-Temporal Analysis, 0302 clinical medicine, fluids and secretions, medicine, Animals, Proximal colon, Intestinal Mucosa, Rats, Wistar, In Situ Hybridization, Fluorescence, Multidisciplinary, Histocytochemistry, Chemistry, Colonic mucus, barrière intestinale, Colonic contents, Mucus, Epithelium, digestive system diseases, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Mucus layer, %22">Fish , cellule épithéliale intestinale, Medicine, 030211 gastroenterology & hepatology, Distal colon
Abstract

The colonic mucus barrier is commonly described as a continuous double layer covering the epithelium, separating the microbiota from the intestinal tissue. This model is currently considered valid throughout the colon. The colon is characterised by regional anatomo-functional specificities such as presence and consistency of contents and location. In this study, we characterised the organisation of the colonic mucus barrier in proximal and distal colon of rodents by histological and FISH staining, taking into account aforementioned specificities. By using longitudinal sections and imaging extensive areas of tissue with and without colonic contents, we have obtained a spatiotemporal overview of mucus organisation in the colon. We describe for the first time that the colonic mucus layer covers the faeces instead of the epithelium in the distal colon. This faecal mucus layer confines the microbiota to the faeces and prevents it from remaining in empty distal colon. In the proximal colon, the mucus did not form a separating layer between bacteria and epithelium. We conclude that the organisation of colonic mucus is reliant on the presence of the colonic content, and the location within the colon. Our findings reopen the discussion on the nature of the colonic mucus barrier.

Published
2017
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8. Lactose and Fructo-oligosaccharides Increase Visceral Sensitivity in Mice via Glycation Processes, Increasing Mast Cell Density in Colonic Mucosa

Author

Sophie Yvon, Mathilde Leveque, Maïwenn Olier, Françoise Guéraud, Helene Eutamene, Vassilia Theodorou, Pauline Rivière, Sylvie Chevolleau, Valérie Tondereau, Jean-François Martin, Jasper B. J. Kamphuis, Laurent Debrauwer, Bruno P. Guiard, Isabelle Jouanin, Maria-Helena Noguer-Meireles, LESUR, Hélène, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Bibliothèque Sainte-Geneviève (BSG), Université Sorbonne Nouvelle - Paris 3, Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), Centre de Recherches sur la Cognition Animale (CRCA), Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim)

Subjects
Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Receptor for Advanced Glycation End Products, Oligosaccharides, Lactose, Advanced Glycation End Products, Irritable Bowel Syndrome, Feces, Mice, chemistry.chemical_compound, 0302 clinical medicine, Glycation, Mast Cells, Intestinal Mucosa, Irritable bowel syndrome, 2. Zero hunger, chemistry.chemical_classification, Gastroenterology, Abdominal Oblique Muscles, Mast cell, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, medicine.anatomical_structure, Hyperalgesia, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Vitamin B Complex, Advanced glycation end-product, 030211 gastroenterology & hepatology, FODMAP, medicine.medical_specialty, Colon, 03 medical and health sciences, Bloating, Internal medicine, medicine, Animals, Gastrointestinal Transit, Mouse Model, Hepatology, Electromyography, Functional Bowel Disorder, Mastocytes, medicine.disease, Diet, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, chemistry, Fermentation, Pyridoxamine
Abstract

International audience; Background & AimsIrritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and erratic bowel habits. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) can reduce symptoms of IBS, possibly by reducing microbial fermentation products. We investigated whether ingestion of FODMAPs can induce IBS-like visceral hypersensitivity mediated by fermentation products of intestinal microbes in mice.MethodsC57Bl/6 mice were gavaged with lactose, with or without the antiglycation agent pyridoxamine, or saline (controls) daily for 3 weeks. A separate group of mice were fed a diet containing fructo-oligosaccharides, with or without pyridoxamine in drinking water, or a normal chow diet (controls) for 6 weeks. Feces were collected and analyzed by 16S ribosomal RNA gene sequencing and bacterial community analyses. Abdominal sensitivity was measured by electromyography and mechanical von Frey filament assays. Colon tissues were collected from some mice and analyzed by histology and immunofluorescence to quantify mast cells and expression of advanced glycosylation end-product specific receptor (AGER).ResultsMice gavaged with lactose or fed fructo-oligosaccharides had increased abdominal sensitivity compared with controls, associated with increased numbers of mast cells in colon and expression of the receptor for AGER in proximal colon epithelium. These effects were prevented by administration of pyridoxamine. Lactose and/or pyridoxamine did not induce significant alterations in the composition of the fecal microbiota. Mass spectrometric analysis of carbonyl compounds in fecal samples identified signatures associated with mice given lactose or fructo-oligosaccharides vs controls.ConclusionsWe found that oral administration of lactose or fructo-oligosaccharides to mice increases abdominal sensitivity, associated with increased numbers of mast cells in colon and expression of AGER; these can be prevented with an antiglycation agent. Lactose and/or pyridoxamine did not produce alterations in fecal microbiota of mice. Our findings indicate that preventing glycation reactions might reduce abdominal pain in patients with IBS with sensitivity to FODMAPs.

Published
2020
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9. Food-grade TiO2 is trapped by intestinal mucus in vitro but does not impair mucin O-glycosylation and short-chain fatty acid synthesis in vivo:implications for gut barrier protection

Author

Pauline Talbot, Joanna M. Radziwill-Bienkowska, Jasper B. J. Kamphuis, Karine Steenkeste, Sarah Bettini, Véronique Robert, Marie-Louise Noordine, Camille Mayeur, Eric Gaultier, Philippe Langella, Catherine Robbe-Masselot, Eric Houdeau, Muriel Thomas, Muriel Mercier-Bonin, CNRS, Université de Lille, MICrobiologie de l'ALImentation au Service de la Santé [MICALIS], Polska Akademia Nauk = Polish Academy of Sciences [PAN], ToxAlim [ToxAlim], Institut des Sciences Moléculaires d'Orsay [ISMO], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institute of Biochemistry and Biophysics, Pawinskiego 5a, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut des Sciences Moléculaires d’Orsay (ISMO), Centre National de la Recherche Scientifique (CNRS), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), and This work was funded by INRA in the frame of the 'Nutrition, Chemical Food Safety, and Consumer Behaviour' division (AlimH priority program 2013)

Subjects
Short-chain fatty acids, Mucus, lcsh:Medical technology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, lcsh:R855-855.5, lcsh:Biotechnology, lcsh:TP248.13-248.65, Gut barrier, Food-grade TiO2, Mucin O-glycans
Abstract

Background Titanium dioxide (TiO2) particles are commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, the risk of gut barrier disruption is an increasing concern because of the presence of a nano-sized fraction. Food-grade E171 may interact with mucus, a gut barrier protagonist still poorly explored in food nanotoxicology. To test this hypothesis, a comprehensive approach was performed to evaluate in vitro and in vivo interactions between TiO2 and intestinal mucus, by comparing food-grade E171 with NM-105 (Aeroxyde P25) OECD reference nanomaterial. Results We tested E171-trapping properties of mucus in vitro using HT29-MTX intestinal epithelial cells. Time-lapse confocal laser scanning microscopy was performed without labeling to avoid modification of the particle surface. Near-UV irradiation of E171 TiO2 particles at 364 nm resulted in fluorescence emission in the visible range, with a maximum at 510 nm. The penetration of E171 TiO2 into the mucoid area of HT29-MTX cells was visualized in situ. One hour after exposure, TiO2 particles accumulated inside “patchy” regions 20 µm above the substratum. The structure of mucus produced by HT29-MTX cells was characterized by MUC5AC immunofluorescence staining. The mucus layer was thin and organized into regular “islands” located approximately 20 µm above the substratum. The region-specific trapping of food-grade TiO2 particles was attributed to this mucus patchy structure. We compared TiO2-mediated effects in vivo in rats after acute or sub-chronic oral daily administration of food-grade E171 and NM-105 at relevant exposure levels for humans. Cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged, irrespective of treatment. Conclusions Food-grade TiO2 is trapped by intestinal mucus in vitro but does not affect mucin O-glycosylation and short-chain fatty acid synthesis in vivo, suggesting the absence of a mucus barrier impairment under “healthy gut” conditions.

Published
2018
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10. Food-grade TiO

Author

Pauline, Talbot, Joanna M, Radziwill-Bienkowska, Jasper B J, Kamphuis, Karine, Steenkeste, Sarah, Bettini, Véronique, Robert, Marie-Louise, Noordine, Camille, Mayeur, Eric, Gaultier, Philippe, Langella, Catherine, Robbe-Masselot, Eric, Houdeau, Muriel, Thomas, and Muriel, Mercier-Bonin

Subjects
Male, Titanium, Glycosylation, Surface Properties, Research, Mucins, Food-grade TiO2, Fatty Acids, Volatile, Mucin O-glycans, Mucus, Short-chain fatty acids, Intestinal Absorption, Gut barrier, Animals, Humans, Nanoparticles, Food Additives, Tissue Distribution, Intestinal Mucosa, Particle Size, Rats, Wistar, Cecum, HT29 Cells
Abstract

Background Titanium dioxide (TiO2) particles are commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, the risk of gut barrier disruption is an increasing concern because of the presence of a nano-sized fraction. Food-grade E171 may interact with mucus, a gut barrier protagonist still poorly explored in food nanotoxicology. To test this hypothesis, a comprehensive approach was performed to evaluate in vitro and in vivo interactions between TiO2 and intestinal mucus, by comparing food-grade E171 with NM-105 (Aeroxyde P25) OECD reference nanomaterial. Results We tested E171-trapping properties of mucus in vitro using HT29-MTX intestinal epithelial cells. Time-lapse confocal laser scanning microscopy was performed without labeling to avoid modification of the particle surface. Near-UV irradiation of E171 TiO2 particles at 364 nm resulted in fluorescence emission in the visible range, with a maximum at 510 nm. The penetration of E171 TiO2 into the mucoid area of HT29-MTX cells was visualized in situ. One hour after exposure, TiO2 particles accumulated inside “patchy” regions 20 µm above the substratum. The structure of mucus produced by HT29-MTX cells was characterized by MUC5AC immunofluorescence staining. The mucus layer was thin and organized into regular “islands” located approximately 20 µm above the substratum. The region-specific trapping of food-grade TiO2 particles was attributed to this mucus patchy structure. We compared TiO2-mediated effects in vivo in rats after acute or sub-chronic oral daily administration of food-grade E171 and NM-105 at relevant exposure levels for humans. Cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged, irrespective of treatment. Conclusions Food-grade TiO2 is trapped by intestinal mucus in vitro but does not affect mucin O-glycosylation and short-chain fatty acid synthesis in vivo, suggesting the absence of a mucus barrier impairment under “healthy gut” conditions. Electronic supplementary material The online version of this article (10.1186/s12951-018-0379-5) contains supplementary material, which is available to authorized users.

Published
2018

11. Toxicity of Food-Grade TiO2 to Commensal Intestinal and Transient Food-Borne Bacteria: New Insights Using Nano-SIMS and Synchrotron UV Fluorescence Imaging

Author

Isabelle Fourquaux, Jacek Bardowski, Jean-Nicolas Audinot, Matthieu Réfrégiers, Frédéric Jamme, Eric Houdeau, Jasper B. J. Kamphuis, Muriel Thomas, Philippe Langella, Muriel Mercier-Bonin, Esther Lentzen, Christel Cartier, Véronique Robert, Magdalena Kowalczyk, Pauline Talbot, Joanna M. Radziwill-Bienkowska, Institute of Biochemistry and Biophysics, Polish Academy of Science, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Luxembourg Institute of Science and Technology (LIST), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institute of Biochemistry & Biophysics, Polish Academy of Sciences (PAN), Mercier-Bonin, Muriel, Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), INRA of the 'Nutrition, Chemical Food Safety and Consumer Behaviour' Division (AlimH priority program), Polska Akademia Nauk = Polish Academy of Sciences (PAN), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
0301 basic medicine, Microbiology (medical), Streptococcus thermophilus, lcsh:QR1-502, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, 010501 environmental sciences, Gut flora, medicine.disease_cause, bacterial toxicity, 01 natural sciences, Microbiology, lcsh:Microbiology, 03 medical and health sciences, Lactobacillus rhamnosus, medicine, media_common.cataloged_instance, European union, food-grade TiO2, Escherichia coli, 0105 earth and related environmental sciences, media_common, cellular and subcellular bioimaging, biology, Chemistry, Lactococcus lactis, technology, industry, and agriculture, biology.organism_classification, medicine.disease, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 13. Climate action, food-borne bacteria, intestinal bacteria, Dysbiosis, Bacteria
Abstract

Titanium dioxide (TiO2) is commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, a risk of intestinal barrier disruption, including dysbiosis of the gut microbiota, is increasingly suspected because of the presence of a nano-sized fraction in this additive. We hypothesized that food-grade E171 and Aeroxyde P25 (identical to the NM-105 OECD reference nanomaterial in the European Union Joint Research Centre) interact with both commensal intestinal bacteria and transient food-borne bacteria under non-UV-irradiated conditions. Based on differences in their physicochemical properties, we expect a difference in their respective effects. To test these hypotheses, we chose a panel of eight Gram-positive/Gram-negative bacterial strains, isolated from different biotopes and belonging to the species Escherichia coli, Lactobacillus rhamnosus, Lactococcus lactis (subsp. lactis and cremoris), Streptococcus thermophilus, and Lactobacillus sakei. Bacterial cells were exposed to food-grade E171 vs. P25 in vitro and the interactions were explored with innovative (nano)imaging methods. The ability of bacteria to trap TiO2 was demonstrated using synchrotron UV fluorescence imaging with single cell resolution. Subsequent alterations in the growth profiles were shown, notably for the transient food-borne L. lactis and the commensal intestinal E. coli in contact with food-grade TiO2. However, for both species, the reduction in cell cultivability remained moderate, and the morphological and ultrastructural damages, observed with electron microscopy, were restricted to a small number of cells. E. coli exposed to food-grade TiO2 showed some internalization of TiO2 (7% of cells), observed with high-resolution nano-secondary ion mass spectrometry (Nano-SIMS) chemical imaging. Taken together, these data show that E171 may be trapped by commensal and transient food-borne bacteria within the gut. In return, it may induce some physiological alterations in the most sensitive species, with a putative impact on gut microbiota composition and functioning, especially after chronic exposure.

Published
2018
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12. A fresh look at IBS-opportunities for systems medicine approaches

Author

Ahmed Albusoda, Annikka V. Polster, Jasper B. J. Kamphuis, H. Wang, N. Barki, T. B. Karunaratne, M. Lazarou, T. V. K. Herregods, Eluisa Perna, T. Pribic, In-Seon Lee, Paul Enck, F. Uhlig, N. Mazurak, Graduate School, Gastroenterology and Hepatology, University of London, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University of Amsterdam [Amsterdam] (UvA), Institut National de la Recherche Agronomique (INRA), Alma Mater Studiorum University of Bologna (UNIBO), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Symbio Pharm GmbH, Partenaires INRAE, Katholieke Univ Leuven, University of Gothenburg (GU), Institut de Recerca, Vall d'Hebron University Hospital [Barcelona], University of Sheffield, NeuroGUT, Albusoda, A., Barki, N., Herregods, T., Kamphuis, J. B. J., Karunaratne, TENNEKOON MUDIYANSELAGE PRASANTHA BUDDHIKA, Lazarou, M., Lee, I., Mazurak, N., Perna, E., Polster, A., Pribic, T., Uhlig, F., Wang, H., and Enck, P.

Subjects
medicine.medical_specialty, Biomedical Research, Systems Analysis, Physiology, [SDV]Life Sciences [q-bio], Systems biology, Alternative medicine, Gastroenterology, Endocrine and Autonomic System, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Internal medicine, medicine, Humans, Education, Graduate, European Union, Irritable bowel syndrome, irritable bowel syndrome, Medical education, Endocrine and Autonomic Systems, business.industry, Information technology, Neurogastroenterology, Medical research, medicine.disease, functional bowel disorders, 3. Good health, functional bowel disorder, Systems medicine, 030211 gastroenterology & hepatology, business, 030217 neurology & neurosurgery
Abstract

International audience; NeuroGUT is a EU-funded initial training network (ITN) of 14 research projects in neurogastroenterology that have employed an equal number of early-stage researchers. Neurogut trainees haveamong other activitiesattended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and were asked to critically review and evaluate the current knowledge on IBS for their respective research activities, and to state what they were missing. Most appreciated were the topics brain imaging of gut activity, the role of the gut microbiota, the pharmacology of gut functions, the IBS-IBD interrelation, the new Rome IV criteria, the role of gas, and the placebo response in functional disorders. Missed were more detailed coverage of high-resolution manometry, functional brain imaging, advanced systems medicine approaches and bioinformatics technology, better sub-classification of IBS patients, and the development of disease biomarkers, extended at the molecular (genetic/epigenetic, proteonomic) level. They summarize that despite excellent specialized research, there is a gap open that should be filled with systems medicine. For this, it would be necessary that medical research learns even more from the data sciences and other basic disciplines, for example, information technology and system biology, and also welcomes a change in paradigm that enhances open sharing of data, information, and resources.

Published
2017
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