Gut microbiota‐associated bile acid deconjugation accelerates hepatic steatosis in ob/ob mice

• Published in: Journal of applied microbiology Vol. 121; no. 3; pp. 800 - 810
• Main Authors: Park, M.‐Y., Kim, S.J., Ko, E.K., Ahn, S.‐H., Seo, H., Sung, M.‐K.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.09.2016
• Subjects: Acids; Animal models; Animals; Bile; bile acids; Bile Acids and Salts - metabolism; Cholesterol; Cholesterol 7-alpha-Hydroxylase - genetics; Cholesterol 7-alpha-Hydroxylase - metabolism; Composition; Digestive system; Digestive tract; Disease Models, Animal; farnesoid X receptor; Fatty liver; Fatty Liver - enzymology; Fatty Liver - genetics; Fatty Liver - metabolism; Fatty Liver - microbiology; Gastrointestinal Microbiome; Gene expression; Humans; Hydroxylase; intestinal microbiota; Intestinal microflora; Intestine; Intestines - metabolism; Intestines - microbiology; Lipid Metabolism; Liver; Liver - enzymology; Liver - metabolism; Liver diseases; Male; mechanisms of action; metabolic processes; Metabolism; Metabolites; Mice; Microbiology; Microbiota; mRNA; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Rodents; Signal transduction; small heterodimer partner; Steatosis; Taurine; intestinal microbiota; metabolic processes; bile acids; farnesoid X receptor; small heterodimer partner; liver diseases; mechanisms of action
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/jam.13158

Aim Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely insufficient. The aim of this study was to elucidate the microbiota‐driven mechanisms involved in the development of nonalcoholic hepatic steatosis. Methods and Results Ob/ob mice and their wild‐type lean control mice were fed an AIN‐93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine‐conjugated BAs compared to their lean controls. The proportions of butyrate‐producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol‐7α‐hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice. Conclusion Microbiota‐associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR‐SHP pathway, thereby accelerating fat synthesis. Significance and Impact of the Study We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.