Microbial Adaptation and Host Signaling: Bacteroides–Bile Acid Interactions in Gut Health

Bile acids are amphipathic molecules synthesized from cholesterol that act not only as digestive agents but also as key signaling molecules regulating host metabolic and immune pathways via FXR (farnesoid X receptor) and TGR5 (G protein-coupled bile acid receptor). In the colon, microbial metabolism profoundly transforms bile acids, modulating their composition, toxicity, and signaling potential. Among gut microbes, Bacteroides spp. are abundant, metabolically versatile, and immunologically active, displaying high resilience to bile acids through efflux pumps, membrane adaptations, and bile salt hydrolase activity (BSH). These bacteria degrade complex polysaccharides via polysaccharide utilization loci, producing short-chain fatty acids and vitamins such as K 2 that reinforce epithelial barrier integrity, modulate immune responses, and influence systemic metabolic and anticancer pathways. While microbial BSHs in other bacteria have been shown to generate bile acid amides (BBAAs) with immunomodulatory and signaling functions, such production has not yet been observed in Bacteroides , though it is plausible given their BSH activity. Strain-specific diversity of Bacteroides and their bile acid interactions underpins both microbial ecology and host physiology. Understanding these mechanisms is essential for microbiota-targeted interventions and therapies, highlighting the metabolic and immunological modulation by Bacteroides –bile acid interplay, bacterial bile resistance strategies, and potential biotechnological and clinical applications.