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

Abstract

The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host. Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also by altered microbiota composition.

The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids

“…As stated earlier, SCFAs influence AMPK and PGC-1α, which regulate the expression of FXR [44]. FXR in turn regulates bile acid synthesis through negative feedback [58]. Furthermore, the microbiota metabolize FXR ligands, thus promoting FXR signaling.…”

“…Those primary bile acids, that are not reabsorbed in the ileum, enter the colon and are microbially converted to secondary bile acids [58]. There is a bidirectional relationship between bile acids and the intestinal microbiota.…”

“…There is a bidirectional relationship between bile acids and the intestinal microbiota. Colonic bile acids can regulate microbial composition as some microbes, like Clostridium difficile, are susceptible to bile acid toxicity, while others require bile acids for growth [58]. In reverse, bile acid metabolism can be influenced by the microbiota.…”

“…FXR was also implicated in lipid and glucose regulation. However, whether this influence is beneficial remains unclear and might be dependent on host diet or site of FXR signaling [58]. Another bile acid receptor is GPR TGR5, which increases thermogenesis and energy expenditure in BAT [60].…”

Can Avicenna Help Manage the Diabetes Epidemic in Central Asia?

“…Recent microbiota transplantation studies from insulin resistant donors to germ-free animals indicate the causal effect of microbiota [55,56]. There is an intensive biochemical and immune "crosstalk" between gut microbiota and the host [57,58]. On the one hand, gut microbiota may contribute to host IR in various ways, including host appetite, energy balance, fat storage, low-grade inflammation etc, [59].…”