Reciprocal interactions between bile acids and gut microbiota in human liver diseases

Abstract

The gut microbiota (GM) play a central role in their host's metabolism of bile acids (BAs) by regulating deconjugation, dehydroxylation, dehydrogenation, and epimerization reactions to generate unconjugated free BAs and secondary BAs. These BAs generated by the GM are potent signaling molecules that interact with BA receptors, such as the farnesoid X receptor and Takeda G-protein-coupled receptor 5. Each BA has a differential affinity to these receptors; therefore, alterations in BA composition by GM could modify the intensity of receptor signaling. Bile acids also act as antimicrobial agents by damaging bacterial membranes and as detergents by altering intracellular macromolecular structures. Therefore, BAs and the GM reciprocally control each other's compositions. In this review, we discuss the latest findings on the mutual effects of BAs and GM on each other; we also describe their roles in the pathophysiology of liver disease progression and potential therapeutic applications of targeting this cross-talk.

Modulation of bile acid profile by gut microbiota in chronic hepatitis B

“…Increasing evidences suggested that bile acids (BAs) play a critical role in chronic liver diseases . The alteration of BAs has been shown to be closely related with various liver diseases, like nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease and cirrhosis and liver cancer .…”

Clean Enzymatic Oxidation of 12α‐Hydroxysteroids to 12‐Oxo‐Derivatives Catalyzed by Hydroxysteroid Dehydrogenase

“…Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) are widely used as pharmaceutical ingredients. [1] UDCA can be employed to treat gallstones, [2] to improve the digestion of fatty acids, to reduce cholesterol absorption and, in cases of cholestatic diseases, to stimulate the liver functions. [3] CDCA has been used for the same treatments, but its side effects made the use in clinical treatment less desiderable than UDCA.…”

Circulating bile acid profiles in Japanese patients with NASH

“…Bile acids are amphipathic molecules that facilitate absorption of dietary fat and lipophilic vitamins in the small intestine. Bile acids also act as signalling molecules controlling glucose, lipid and energy homoeostasis by activating farnesoid X receptor (FXR) and Takeda G‐protein receptor‐5 (TGR5) . Bile acids have differing potencies for activating FXR and TGR5.…”

“…Bile acids are synthesised in the hepatocytes as primary bile acids (cholic acid and chenodeoxycholic acid in humans), which are transformed to secondary bile acids (deoxycholic acid and lithocholic acid) with multistep 7α‐dehydroxylation by intestinal bacteria (Figure ). The human gut microbiome may have an impact on FXR/TGR5 signalling by manipulating the availability and strength of bile acid ligands through bile acid metabolism . Recent evidence shows a role for the gut microbiome in insulin resistance, obesity and associated metabolic disturbances, raising interest in the gut microbiome's relationship with NAFLD/NASH pathogenesis .…”