Underestimated and Overlooked Factors in PBC Progression: Bacterial and Fungal Infections

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis, which can progress to end-stage liver disease and even hepatocellular carcinoma. Its onset is typically triggered by complex interactions between genetic and environmental factors. In recent years, epidemiological and mechanistic studies have highlighted bacterial and fungal infections as potential key environmental factors in PBC pathogenesis. Bacteria may be associated with PBC autoimmunity through mechanisms such as molecular mimicry. Gut microbiota dysbiosis has been linked to aberrant immune recognition, altered metabolites, and intestinal barrier disruption, which may contribute to the aggravation of liver injury. Case reports of fungal infections suggest an association with poor prognosis in PBC, although the underlying mechanisms remain to be elucidated. This review systematically summarizes existing clinical epidemiological data, microbiome association studies, and mechanistic evidence; synthesizes the possible molecular mechanisms linking bacterial infections to PBC development and progression; discusses the potential role of the gut microbiota in PBC progression; and analyzes the possible molecular mechanisms underlying the poor prognosis associated with fungal infections in PBC. This study aims to provide valuable insights for developing optimal prevention, diagnosis, and treatment strategies targeting bacterial and fungal infections in PBC.