Role of bile acids in liver diseases mediated by the gut microbiome

Abstract

The intensive crosstalk between the liver and the intestine performs many essential functions. This crosstalk is important for natural immune surveillance, adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites. The interaction between the gut microbiome and bile acids is bidirectional. The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes. Similarly, bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system. The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases, especially liver diseases. As essential mediators of the gut-liver crosstalk, bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1. Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases. We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

Bile Acid Dysregulation Is Intrinsically Related to Cachexia in Tumor-Bearing Mice

“…Furthermore, the hepatic bile acid profile highlights a decrease in total secondary bile acids (especially for TDCA), arising from bacterial transformation, occurring only in C26 cachectic mice. Consistent with our previous work showing that the gut microbiota appears as a novel actor in cancer cachexia [ 46 , 47 ], and based on our knowledge of the bile acids-microbiota crosstalk [ 10 , 11 , 48 ], we speculate that the disruption in the hepatobiliary secretion, supported here by the functional measurement of the bile flow, may also contribute to the gut bacterial dysbiosis found in cancer cachexia. Vice versa, gut bacterial dysbiosis may contribute to the altered bile acid profile.…”

Pre-Existing Microbiome Signature in a SARS-CoV-2 Discordant Family

“…Gut microbiota influence and modulate host immune responses [ 9 ]. For example, crosstalk between the liver and the intestine is essential for natural immune surveillance, adaptive immune response regulation, and nutrient metabolism, and elimination of toxic bacterial metabolites [ 10 ]. Additionally, in HIV patients, the altered gut microbiome increases disease susceptibility [ 11 ].…”

Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease

“…In regard to the host, some secondary bile acids, e.g., lithocholic acid [LCA] and deoxycholic acid [DCA]), exhibit a high affinity for the farnesoid x receptor (FXR) and G proteincoupled bile acid receptor (TGR5, a.k.a., GPBAR1), which regulate glucose, lipid, and bile acid homeostasis [34][35][36]. In human NAFLD, the secondary bile acid metabolism is disrupted with bile acid analogs that target the FXR and TGR5 signaling pathways under development for the treatment of liver disease [22,31,37]. Previous work demonstrated that the serum levels of LCA and DCA increased following TCDD treatment suggesting enrichment for the microbial bile acid metabolism [9].…”

“…Bile acids also affect the gut microbiome by exerting antimicrobial activity [31]. Conversely, the gut microbiota play critical roles in host bile acid homeostasis through microbial metabolism that qualitatively and quantitatively impact bile acid composition with consequences for bile acid activated signaling pathways in the host.…”