Gut and Biliary Microbiota in Gallstone Subtypes: Microbial Signatures, Lithogenic Mechanisms, and Translational Implications—A Narrative Review

Gallstone disease encompasses biologically distinct stone subtypes, and the contribution of gut and biliary microorganisms appears to vary substantially among them. This narrative review examines the microbial features and mechanistic evidence associated with cholesterol, black pigment, and brown pigment stones. PubMed/MEDLINE and Europe PMC were searched from inception to August 2026, with particular attention to stone classification, sampling compartment, analytical methodology, and functional evidence. For cholesterol gallstones, the most consistent microbiota-related findings involve the gut–bile acid axis rather than an infection-dominant biliary microbiome. Enhanced microbial 7α-dehydroxylation can increase secondary bile acids, alter bile acid hydrophobicity, and promote intestinal cholesterol absorption and biliary cholesterol supersaturation. Brown pigment stones show a much closer relationship with biliary infection. Escherichia coli, Klebsiella spp., Enterococcus spp., and Enterobacter spp. have been implicated in infected bile or pigment-stone settings. By comparison, black pigment stones are more strongly linked to increased host bilirubin load, endogenous β-glucuronidase activity, and non-enzymatic bilirubin deconjugation, and current evidence does not support bacterial infection as an obligatory driver. Mixed stones appear to occupy an intermediate or overlapping phenotype, with culture-based studies reporting bacterial burdens between those of cholesterol and pigment stones. Overall, the available evidence supports subtype-specific rather than uniform microbial contributions to gallstone formation. Distinguishing true lithogenic mechanisms from secondary colonization will require studies using composition-defined stones, compartment-specific sampling, rigorous low-biomass controls, and direct functional validation.