Bile Acids as Key Mediators of the Gut Microbiota–Immune Axis: Potential Biomarker and Therapeutic Perspectives

Abstract

Bile acids (BAs), long recognized for their role in lipid digestion, have recently emerged as key signaling molecules at the interface of host metabolism, immunity, and gut microbiota (GM). BAs are synthesized in hepatocytes and subsequently extensively modified by microbial enzymes in the gut, producing a diverse and dynamic pool that strongly shapes the GM-immune axis. Through activation of receptors such as the Farnesoid X receptor and the G protein-coupled receptor TGR5, BAs regulate inflammation, metabolic pathways, and intestinal immune homeostasis, particularly influencing the balance between regulatory T cells and pro-inflammatory Th17 cells. Microbial transformations, primarily deconjugation and 7α-dehydroxylation, further diversify BA species, modulating receptor affinities and immunoregulatory functions. Dysbiosis-associated alterations in these processes contribute to the pathogenesis of inflammatory disorders, including inflammatory bowel disease (IBD). Consequently, BAs are increasingly recognized as promising biomarkers for monitoring disease activity and predicting therapeutic response, although validation in standardized, prospective cohorts remains necessary. Recent advances in high-resolution analytical techniques, notably high- and ultra-performance liquid chromatography coupled with tandem mass spectrometry (HPLC- and UPLC-MS/MS), have enabled precise, high-throughput quantification of BA species in serum and fecal samples. These methods both deepen mechanistic understanding of BA-mediated immunomodulation and support the development of GM- and BA-targeted therapies. This review emphasizes the central role of BAs in GM-immune axis regulation, delineates their complex interplay with host and microbial factors, and surveys evolving analytical strategies that facilitate their study in health and disease.

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