Gut microbiota alterations in primary biliary cholangitis: a systematic review and meta-analysis

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease. Increasing evidence suggests that gut microbiota dysbiosis may contribute to its pathogenesis and progression. However, existing studies are limited by small sample sizes, methodological inconsistency, and the lack of quantitative synthesis, resulting in insufficient consolidated evidence.

This systematic review and meta-analysis aimed to evaluate alterations in the gut microbiota of patients with PBC.

PubMed, Web of Science, Embase, and the Cochrane Library were systematically searched from inception to January 23, 2026. Outcomes included alpha-diversity indices, beta diversity, and taxonomic alterations. Meta-analyses were performed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Sensitivity analysis, subgroup analysis, and meta-regression were conducted to explore potential sources of heterogeneity.

Of 1,326 records screened, 10 studies involving 1,057 participants (607 patients with PBC and 450 controls) were included, and all studies had Newcastle-Ottawa Scale scores of at least 7. Compared with controls, patients with PBC had a significantly lower Shannon index (SMD = -0.72, 95% CI: -1.22 to -0.22, p < 0.001; I² = 91.0%) and fewer operational taxonomic units (OTUs) (SMD = -0.57, 95% CI: -0.81 to -0.33, p < 0.001; I² = 45.4%), whereas the Simpson index was significantly higher (SMD = 0.81, 95% CI: 0.40 to 1.21, p < 0.001; I² = 44.4%). After exclusion of an outlier study, the Chao1 index was also significantly reduced (SMD = -0.38, 95% CI: -0.63 to -0.15, p < 0.001; I² = 22.6%), while no significant difference was observed for the ACE index. Most studies also reported significant differences in beta diversity between patients with PBC and healthy controls. Taxonomic analysis showed enrichment of Neisseria, Klebsiella, Veillonella, Bifidobacterium, Lactobacillus, Streptococcus, Enterococcus, Clostridium, and Escherichia, whereas Bacteroides, Faecalibacterium, Blautia, Roseburia, Coprococcus, Oscillospira, and Morganella were generally depleted in PBC. Meta-regression did not identify age, geographic region, or sequencing platform as significant sources of heterogeneity.

PBC is associated with gut microbiota alterations, characterized by reduced alpha diversity, altered community structure, and taxonomic remodeling. Longitudinal and functional studies are needed to clarify causality, mechanisms, and clinical applications.