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Microbiote intestinal et stéatopathie métabolique
Institution:1. Inserm UMRS U996 - Inflammation, Cytokines and Immunopathology, DHU Hepatinov, Labex LERMIT, 32, rue des carnets, 92140 Clamart, France;2. Université Paris-Sud, université Paris-Saclay, 92140 Clamart, France;3. Service d’hépatogastroentérologie et nutrition, hôpital Antoine-Béclère, AP–HP, 157, rue de la Porte-de-Trivaux, 92140 Clamart, France;4. Institut De Recherche Servier (IDRS), 11, rue des Moulineaux, 92150 Suresnes, France;1. Laboratoire de Biochimie, centre hospitalo universitaire Habib Bourguiba, avenue El-Ferdaous, 3029 Sfax, Tunisie;2. Unité de recherche Bases moléculaires de la pathologie humaine, faculté de médecine de Sfax, avenue Majida-Boulila, 3029 Sfax, Tunisie;3. Service de gastro-entérologie, centre hospitalo universitaire Hédi-Chaker, avenue Majida-Boulila, 3029 Sfax, Tunisie;4. Service de rhumatologie, centre hospitalo universitaire Hédi-Chaker, avenue Majida-Boulila, 3029 Sfax, Tunisie;4. MaaT Pharma, 69007 Lyon, France;5. Hôpital Bichat, AP–HP, université Paris Diderot, 92240 Malakoff, France;6. Astra Zeneca, 92400 Courbevoie, France;7. Hôpital Cochin, AP–HP, 75014 Paris, France;8. Institut Mérieux, 69002 Lyon, France;9. Enterome, 75011 Paris, France;10. Merck Sharpe & Dohme France, 92400 Courbevoie, France;11. Inserm U1019, institut Pasteur, 59019 Lille, France;12. Pfizer, 75668 Paris, France;13. PRI Pharmabiotic Research Institute, 15000 Aurillac, France;14. Ipsen, 92650 Boulogne Billancourt, France;15. Leem/ARIIS, 75858 Paris, France;p. Département de la recherche clinique et du développement, hôpital Saint-Louis, AP–HP, 75010 Paris, France;q. Bioaster, 69007 Lyon, France;r. Inserm, 75654 Paris, France;s. Nestlé Institute of Health Sciences SA, 1015 Lausanne, Switzerland;t. INRA, 78352 Jouy-en-Josas, France;1. Institut national de la recherche agronomique (INRA), Metagenopolis, 78350 Jouy-en-Josas, France;2. Sanofi R&D, unité sciences translationnelles, 13, quai Jules-Guesde, 94403 Vitry sur Seine, France;3. Takeda France, 92977 La Defense, France
Abstract:Non alcoholic fatty liver disease or NAFLD is a disease with a large spectrum of liver injury that could appear in overweight or obese individuals with a metabolic syndrome. However, among overweight or obese, only a subset of individuals develops severe forms of NAFLD. Thus, the susceptibility of NAFLD is related to cofactors that could be protective or conversely noxious. Studies carried out in rodent models have demonstrated that the intestinal microbiota is a cofactor with a causal role in NAFLD. The bacterial patterns as well as the metabolites produced by intestinal bacteria are directly involved in the mediation of their effects, although the mechanisms are far from being fully identified. Changing intestinal microbiota by using fibers, prebiotics or probiotics can prevent or improve NAFLD in murine models. The translation of these data to human therapeutics is encouraging but remains limited. Indeed, there is clearly a dysbiosis associated with the different stages of NAFLD. The first clinical trials performed in patients to improve NAFLD showed beneficial effects although their analysis remains complicated given the many confounding factors, such as the use of metformin or proton inhibitors. A first clinical trial using a metabolite from Akkermansia muciniphila, suggests that new therapeutic approaches will emerge in the coming years based either on the modulation of the intestinal microbiota directly or on the modulation of intestinal microbiota targets.
Keywords:NAFLD  Intestinal microbiota  NASH  Dysbiosis
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