Versatile Triad Alliance: Bile Acid, Taurine and Microbiota

Abstract

Taurine is the most abundant free amino acid in the body, and is mainly derived from the diet, but can also be produced endogenously from cysteine. It plays multiple essential roles in the body, including development, energy production, osmoregulation, prevention of oxidative stress, and inflammation. Taurine is also crucial as a molecule used to conjugate bile acids (BAs). In the gastrointestinal tract, BAs deconjugation by enteric bacteria results in high levels of unconjugated BAs and free taurine. Depending on conjugation status and other bacterial modifications, BAs constitute a pool of related but highly diverse molecules, each with different properties concerning solubility and toxicity, capacity to activate or inhibit receptors of BAs, and direct and indirect impact on microbiota and the host, whereas free taurine has a largely protective impact on the host, serves as a source of energy for microbiota, regulates bacterial colonization and defends from pathogens. Several remarkable examples of the interaction between taurine and gut microbiota have recently been described. This review will introduce the necessary background information and lay out the latest discoveries in the interaction of the co-reliant triad of BAs, taurine, and microbiota.

Keywords: bile acids; microbiota; taurine.

Figure 1

Regulation of bile acids (BA) metabolism. BAs are produced in the liver by modifying cholesterol with a series of CYP enzymes. The liver also produces taurine, which can be conjugated to BAs by BAL (BA CoA-ligase) and BAT (BA CoA:amino acid N-acyltransferase) enzymes. BAs secreted from the liver into the intestine undergo deconjugation and a series of modifications generating an array of secondary BAs. The deconjugated taurine is taken up by TauT and BAs by IBAT (ileal BA transporter) and OSTα-OSTβ (organic solute transporter α-β). Afterward, BAs are recirculated via entero-hepatic circulation and transported into the liver by NTCP (sodium-dependent taurocholate co-transporting peptide) and OATP (organic anion-transporting polypeptides). The presence of BAs activates their receptors. Upon stimulation, intestinal TGR5 promotes GLP-1 (glucagon-like-peptide-1) and PYY (peptide-YY) production. At the same time, nuclear receptor FXR (farnesoid X receptor) regulates the expression of genes connected with BAs transport and signaling. One of FXR target proteins, FGF15 (fibroblast growth factor 15), transfers the signal of BAs abundance from the intestine to the liver. Consequently, it reduces BAs’ production and transport via JNK/ERK signaling pathway or together with SHP (small heterodimer partner). Additionally, hepatic FXR surveys for the levels of BAs and signals to adjust BAs’ biosynthesis, conjugation, and transport.

Figure 2

Summary of the roles of BAs-derived taurine. Various bacterial strains have the capacity to deconjugate BAs. The released unconjugated BAs modulate gut microbiota composition, signal various functions through its receptors, and impact nutrient uptake. BAs are also submitted modifications by microbiota, including reconjugation and generation of secondary BAs. The faith of taurine released from conjugated BAs in the intestine can follow various paths. It is metabolized for energy and generates secondary metabolites, which, such as H₂S, may play a role in interacting with bacteria, inflammation, and oxidative stress. Taurine also signals within the intestine to extinguish inflammation and prevent pathogens colonization. Additionally, various compounds can conjugate taurine, and, e.g., conjugation to GSH enhances taurine uptake during caloric restriction. The exported taurine plays various roles in other organs, particularly in the nerve system as well as in mitochondria all over the body.