Sex Differences in Gut Microbiome in High-Fat-Diet Fed Rats

Abstract Background: Sex differences in obesity and related metabolic diseases are well recognized, however, the mechanism has not been elucidated. Gut microbiota and its metabolites may play a vital role in the development of obesity and metabolic diseases. The aim of the present study was to investigate sex differences in gut microbiota and its metabolites in a high-fat-diet (HFD) obesity rats and identify microbiota genera potentially contributing to such differences in obesity and non-alcoholic fatty liver disease (NAFLD) susceptibility.Methods: Sprague–Dawley rats were divided into four groups (eight animals per group): (1) male rats on a normal diet (MND), (2) male rats on HFD (MHFD), (3) female rats on a normal diet (FND), and (4) female rats on HFD (FHFD). Body weight, liver pathology, gut microbiota and short/medium chain fatty acids in colon contents were compared between different sexes.Results: HFD induced more body weight gain and fat storage in female rats, however, lower hepatic steatosis in FHFD than in MHFD rats was observed. When considering gut microbiota composition, FHFD rats had lower microbiome diversity than MHFD. A significant increase of Firmicutes phylum, along with Bilophila and Blautia genus was detected in MHFD rats, as compared with FHFD, which showed increased relative abundance of Murimonas. Moreover, propionic and lauric acid levels were higher in FHFD than those in MHFD rats. Conclusions: HFD induced sex-related alterations in gut microbiome and fatty acids. Furthermore, the genus Bilophila, Blautia and Murimonas might contribute to sex differences observed in obesity and NAFLD susceptibility.