Gut microbiota-associated bile acid deconjugation accelerates hepatic steatosis in ob/ob mice.
OBJECTIVE
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.


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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Department of Food and Nutrition Education, Graduate School of Education, Soonchunhyang University, Asan, Chungnam, Korea.
M-Y
MY
Park
Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
S J
SJ
Kim
Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
E K
EK
Ko
Collage of Pharmacy, Kangwon National University, Chuncheon, Korea.
S-H
SH
Ahn
Department of Drug Discovery Platform Technology, Korea Research Institute of Chemical Technology, Daejeon, Korea.
H
H
Seo
Department of Food and Nutrition, Sookmyung Women's University, Seoul, Korea.
M-K
MK
Sung
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism
D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2; D002790:Cholesterol 7-alpha-Hydroxylase
bile acids; farnesoid X receptor; intestinal microbiota; liver diseases; mechanisms of action; metabolic processes; small heterodimer partner