Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia

Autor: Philippe J. Sansonetti, Matthieu Rouland, Maria Rescigno, Lucie Cagninacci, Nathalie Vergnolle, Sandra Guilmeau, Juliette Mouriès, Latif Rachdi, Lucie Beaudoin, Azadeh Saffarian, Agnès Lehuen, Dalale Gueddouri, Anne-Françoise Burnol, Ute Christine Rogner, Asmaa Tazi, Ophélie Rouxel, Léo Bertrand, Thierry Pedron
Přispěvatelé: Centre National de la Recherche Scientifique (CNRS), 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), Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humanitas University [Milan] (Hunimed), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LabEx Inflamex, This work was supported by Agence Nationale de la Recherche (ANR-11-IDEX-0005-02 Laboratory of Excellence INFLAMEX and ANR-17-CE14-0002-01 Diab1MAIT), Fondation pour la Recherche Médicale (DEQ20140329520 and EQU201903007779), the INSERM crosscutting program on microbiota and the European Foundation for the Study of Diabetes–Juvenile Diabetes Research Foundation–MR, OR and LBer were supported by the French Ministry of Research., ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-17-CE14-0002,Diab1MAIT,Rôle des cellules MAIT dans le diabète de type 1 chez l'homme et la souris(2017), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation pour la Recherche Medicale (DEQ20140329520 and EQU201903007779), European Foundation for the Study of Diabetes-Juvenile Diabetes Research Foundation-MR, OR and LBer are supported by the French Ministry of Research, the INSERM crosscutting program on microbiota is supported by the French Ministry of Research
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
endocrine system diseases
medicine.medical_treatment
Segmented filamentous bacteria
intestinal microbiology
Inflammation
Gut flora
digestive system
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
Diabetes Mellitus
medicine
Animals
Intestinal Mucosa
Autoimmune disease
Bacteria
biology
Insulin
digestive
oral
and skin physiology
Gastroenterology
Interleukin
Epithelial Cells
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
biology.organism_classification
medicine.disease
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Gastrointestinal Microbiome
3. Good health
Disease Models
Animal
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Diabetes Mellitus
Type 1
030104 developmental biology
Hyperglycemia
030220 oncology & carcinogenesis
Immunology
mucosal immunity
Cytokines
Dysbiosis
[SDV.IMM]Life Sciences [q-bio]/Immunology
medicine.symptom
[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Gut
Gut, BMJ Publishing Group, 2021, pp.gutjnl-2020-323664. ⟨10.1136/gutjnl-2020-323664⟩
Gut, 2022, 71 (2), pp.296-308. ⟨10.1136/gutjnl-2020-323664⟩
Gut, BMJ Publishing Group, 2022, 71 (2), pp.296-308. ⟨10.1136/gutjnl-2020-323664⟩
ISSN: 0017-5749
1468-3288
Popis: ObjectiveType 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β-cells producing insulin. Both T1D patients and animal models exhibit gut microbiota and mucosa alterations, although the exact cause for these remains poorly understood. We investigated the production of key cytokines controlling gut integrity, the abundance of segmented filamentous bacteria (SFB) involved in the production of these cytokines, and the respective role of autoimmune inflammation and hyperglycaemia.DesignWe used several mouse models of autoimmune T1D as well as mice rendered hyperglycaemic without inflammation to study gut mucosa and microbiota dysbiosis. We analysed cytokine expression in immune cells, epithelial cell function, SFB abundance and microbiota composition by 16S sequencing. We assessed the role of anti-tumour necrosis factor α on gut mucosa inflammation and T1D onset.ResultsWe show in models of autoimmune T1D a conserved loss of interleukin (IL)-17A, IL-22 and IL-23A in gut mucosa. Intestinal epithelial cell function was altered and gut integrity was impaired. These defects were associated with dysbiosis including progressive loss of SFB. Transfer of diabetogenic T-cells recapitulated these gut alterations, whereas induction of hyperglycaemia with no inflammation failed to do so. Moreover, anti-inflammatory treatment restored gut mucosa and immune cell function and dampened diabetes incidence.ConclusionOur results demonstrate that gut mucosa alterations and dysbiosis in T1D are primarily linked to inflammation rather than hyperglycaemia. Anti-inflammatory treatment preserves gut homeostasis and protective commensal flora reducing T1D incidence.
Databáze: OpenAIRE
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