Abstract
Biotransformation of host bile salts by gut microbes results in generation of secondary bile salt species that have biological and physicochemical properties that are distinct from the parent compounds. There is increased awareness that a bile salt–gut microbiome axis modulates various processes in the host, including innate and adaptive immunity, by interaction of microbial bile salt metabolites with host receptors. Omics and targeted approaches have vastly expanded the number and repertoire of secondary bile salt species. A new class of microbial bile salt metabolites was reported in 2020 and comprises bile salts that are conjugated by microbial enzymes. Amino acids other than those employed by host enzymes (glycine and taurine) are used as substrates in the formation of these microbial bile salt conjugates (MBSCs). Leucocholic acid, phenylalanocholic acid and tyrosocholic acid were the first MBSCs identified in mice and humans. The number of distinct MBSCs is now approaching 50, with variation both at the level of bile salt and amino acid employed for conjugation. Evidence is emerging that MBSC generation is a common feature of human gut bacteria, and initial links with disease states have been reported. In this review, we discuss this intriguing new class of secondary bile salts, with yet enigmatic function.
Highlights
The gut is a complex ecosystem that harbors a wide variety of microorganisms that are intricately linked to host health and disease
Hepatic Fxr target gene induction was observed after repeated gavage (4 dosages, 72 h), with elevated expression of Shp seen in mice receiving microbial bile salt conjugate (MBSC) [9]
The pioneering study of Quinn et al that was published in March 2020 resulted in the identification of three MBSCs and two Clostridium bolteae strains capable of synthesizing them
Summary
The gut is a complex ecosystem that harbors a wide variety of microorganisms that are intricately linked to host health and disease. Selection of taurine and glycine as exclusive amino acid substrates in hepatic N-amidation of bile salts relates to the resistance of the respective conjugates to degradation by host enzymes encountered in their enterohepatic trajectory, e.g., carboxypeptidases in pancreatic juice and membranebound (carboxy) peptidases in the small intestinal mucosa [5]. This concept arose from studies with synthetic bile salt conjugates that were susceptible to cleavage by pancreatic carboxypeptidase unless glycine or taurine was used for conjugation, with conjugates of these particular amino acids being largely inert to enzymatic degradation [5].
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