The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis

Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is unknown. We investigated the effect of dietary lipid composition on human microbiota in an observational study and combined diet experiments with microbiota transplants to study lipid-microbiota interactions and liver status in mice. In humans, low intake of saturated fatty acids (SFA) was associated with increased microbial diversity independent of fiber intake. In mice, cecum levels of SFA correlated negatively with microbial diversity and were associated with a shift in butyrate and propionate producers. Mice fed poorly absorbed SFA had improved metabolism and liver status. These features were transmitted by microbial transfer. Diets enriched in n-6- and/or n-3-polyunsaturated fatty acids were protective against steatosis but had minor influence on the microbiota. In summary, we find that unabsorbed SFA correlate with microbiota features that may be targeted to decrease liver steatosis. C57Bl/6 8 weeks old male mice were maintained under standard specific-pathogen-free (SPF) conditions. Mice were fed irradiated isocaloric diets differing only in their composition of fat for 9 weeks: Envigo TD.180343 (diet A), TD.180344 (diet B), TD.180345 (diet C), TD.180346 (diet D), TD.180347 (diet E), TD.180348 (diet F), TD.180349 (diet G); 42% kcal fat, 0.2% weight total cholesterol. A milk fat containing diet (Envigo TD.180342) that has previously been shown to induce steatosis served as reference (Ref) diet.