Dietary fat‐induced taurocholic acid production promotes pathobiont and colitis in IL‐10−/− mice

Abstract

The composite human microbiome of Western populations has changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk derived)‐fat (MF) but not polyunsaturated (safflower oil)‐fat (PUFA) changes the conditions for microbial assemblage and promotes expansion of a rare, immunogenic, sulfite‐reducing pathobiont, Bilophila wadsworthia. This was associated with a proinflammatory TH1 immune response and the development of colitis in genetically susceptible IL‐10−/− mice. Because MF promotes the formation of taurine‐conjugated hepatic bile acids (a sulfur source for B. wadsworthia), we examined the possibility that the MF effects are mediated by changes in bile composition. Only bile obtained from MF‐fed mice promoted B. wadsworthia growth in vitro. In addition, a bloom of B. wadsworthia and development of colitis was seen when mice were fed a low‐fat (LF) diet supplemented with taurocholic, but not with glycocholic acid. Furthermore, when germ‐free IL‐10−/− mice were monoassociated with B. wadsworthia, the bacteria survived only when provided with the MF diet or taurocholic acid, and resulted in colitis, which was not observed when MF or taurocholic acid were fed alone. Together these data show that dietary fats differ in their effects on the host microbiota and immune system. The data also provide a plausible mechanistic basis by which Western type diets high in saturated fats may increase the prevalence of complex immune‐mediated diseases like inflammatory bowel diseases in genetically susceptible hosts.