Sex Difference is a Determinant of Gut Microbes and Their Metabolites SCFAs/MCFAs in High Fat Diet Fed Rats

There are gender differences in obesity and related metabolic diseases, but the mechanism of these differences has not been elucidated. Gut microbiota has been recently recognized as a pivotal determinant of obesity and related diseases. The aim of the present study was to investigate sex differences in gut microbiota and its metabolites in an obesity rat model induced by prolonged high-fat-diet (HFD) feeding. In this study, male and female Sprague-Dawley rats were fed normal chow or HFD for 16 weeks (n = 8 for each group). We found that comparing with male rats on HFD (MHFD), female rats on HFD (FHFD) gained more body weight percentage, while had lower body weight gain efficiency and less severity of hepatic steatosis. HFD induced decreased taxon diversity and richness of gut microbiota, and FHFD group had even lower diversity than MHFD group. Among key genera, HFD induced increased Bilophila in male rats but not in female rats. Compared with the MHFD group, FHFD group possessed increases of Akkermansia and Murimonas, and decreases of Acetanaerobacterium, Bacteroides, Bilophila, Blautia and Romboutsia. The levels of total SCFAs in colon contents were increased in tendency in HFD-fed rats of both sexes. FHFD group had increased propionate and decreased ratio of acetate to propionate and butyrate than MHFD group. For MCFAs, HFD induced increases in undecanoic acid and lauric acid in female rats but not in males. In conclusion, HFD induced sex-related alterations in gut microbiome and short/medium-chain fatty acids in rats.