Interactions between Diet, Bile Acid Metabolism, Gut Microbiota, and Inflammatory Bowel Diseases

Abstract

The composite human gut microbiomes of Western populations have changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Diets high in saturated fats and refined sugars and low in fiber are leading candidates for these events and for triggering the increased prevalence of immune-mediated diseases like inflammatory bowel disease (IBD). Our studies have shown that consumption of a ‘Western' diet high in saturated (milk-derived) fat (MF) or n-6 polyunsaturated (safflower oil) fat have similar effects on the structure of the colonic microbiome of wild-type and IL- 10^-/- mice, characterized by increased Bacteroidetes and decreased Firmicutes. However, the MF diet uniquely promotes the expansion of an immunogenic sulfite-reducing pathobiont, Bilophila wadsworthia, a member of the Deltaproteobacteria and minor component of the gut microbiome. This bacterial bloom results from a MF diet-induced shift in hepatic conjugation of bile acids, from glycocholic to taurocholic (TC) acid, which is important for solubilizing the more hydrophobic MF diet. However, it is also responsible for delivery of taurine-derived sulfur to the distal bowel, promoting the assemblage of bile-tolerant microbes such as B. wadsworthia. The bloom of this species promotes a Th1-mediated immune response and the development of colitis in IL-10^-/- mice. A similar bloom of B. wadsworthia is seen when IL-10^-/- mice are fed a low-fat diet supplemented with TC. B. wadsworthia colonization of monoassociated germ-free IL-10^-/- mice was dependent on the host consuming either a high-saturated MF diet or the gavage with TC. Together, these data provide a plausible explanation for the link between diseases such as IBD and dietary-mediated selection of gut microbial pathobionts in genetically susceptible hosts. With this knowledge, it may be possible to mitigate the bloom of these types of pathobionts by modifying the conjugation states of bile acids.

Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism

“…An increase in B. wadsworthia was observed when IL-10 À/À mice on chow diet were gavaged with TCA for a week, and almost the same bloom of B. wadsworthia was observed as in those mice on milk-fat diet. Furthermore, supplementation of the diet with omega-3 fish oil is supposed to inhibit the bloom of B. wadsworthia, most likely because of alterations in the bile acid composition (Devkota and Chang, 2015). This is in agreement with a recent study demonstrating that the abundance of Bilophila is reduced after feeding mice with fish oil rather than lard as fat source (Caesar et al, 2015).…”

Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

“…The influence of environment on IBD is best illustrated by the disproportionately high prevalence of IBDs in developed countries, and high rates of disease discordance amongst identical twins (50% for CD, 10% for UC) 7 . High fat diet, smoking, and early exposure to antibiotics have all been implicated as contributing to IBD susceptibility 12-14 . The best-established link between IBD susceptibility and the environment is the microbiota, a term that refers to the vast community of enteric bacteria that persistently colonize the mammalian GI tract 2,6 .…”

Bile acids in drug induced liver injury: Key players and surrogate markers

“…The mutual effects of BAs on the intestinal microflora and vice versa have repeatedly been reported [54].…”