Bile acids and the gut microbiome

Abstract

Purpose of review: We examine the latest research on the emerging bile acid-gut microbiome axis and its role in health and disease. Our focus revolves around two key microbial pathways for degrading bile salts, and the impact of bile acid composition in the gut on the gut microbiome and host physiology.

Recent findings: Bile acid pool size has recently been shown to be a function of microbial metabolism of bile acids in the intestines. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. Bile acids are emerging as regulators of the gut microbiome at the highest taxonomic levels. The role of bile acids as hormones and potentiators of liver cancer is also emerging.

Summary: The host and microbiome appear to regulate bile acid pool size. The host produces a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of farnesoid X receptor (FXR) in intestine and liver. Members of the microbiome utilize bile acids and their conjugates resulting in agonism of FXR in intestine and liver resulting in a smaller, unconjugated hydrophobic bile acid pool. Hydrophilicity of the bile acid pool is associated with disease states. Reduced bile acid levels in the gut are associated with bacterial overgrowth and inflammation. Diet, antibiotic therapy, and disease states affect the balance of the microbiome-bile acid pool.

Figure 1. Accumulation of deoxycholic acid in the bile acid pool of Veterans Affairs patients

Bile acid 7α-dehydroxylation by intestinal clostridia result in hydrophobic bile acids that can return to the liver via the portal circulation and accumulate in the human bile acid pool. Adapted from Ridlon et al (2006) [14].

Figure 2

Gut Microbiota Influence bile acid pool size in mice through metabolism of FXR-antagonist, tauro-β-muricholic acid. Panel A: Inhibition of intestinal FXR by T-βMCA increases bile acid pool size through enhanced bile acid synthesis in the liver and efficient enterohepatic circulation due to high levels of apical sodium bile salt transporter (IBAT; SLC10A2) in the ileum. Panel B: Metabolism of T-βMCA, and production of FXR-agonists including secondary bile acids by gut microbiome results in FXR-induced release of FRF-15 in the intestine and inhibition of the rate-limiting enzyme in bile acid synthesis, cholesterol 7α-hydroxylase (CYP7a1) in the liver. Reduction in bile acid synthesis coupled with downregulation of ASBT results in reduction in bile acid pool size.

Figure 3. Metabolism of bile salt, taurocholic acid, by gut microbiome

Gut microbes in the ileum and large bowel deconjugate bile salts to free bile acids by bile salt hydrolase. Taurine, due to sulfite moiety, can provide pathobionts in the gut with a terminal electron acceptor, allowing for their growth and expansion in the gut [26]. High-fat diet is associated with increased taurine-conjugation in humans [28]. Free primary bile acids are further metabolized to toxic secondary bile acids that can accumulate in the bile acid pool in humans [see Figure 1] and alter host physiology.