The Microbiome-Gut-Liver Axis Drives Post-Kasai Fibrosis in Biliary Atresia: From Mechanism to Precision Intervention

Biliary atresia (BA) remains the most devastating fibro-inflammatory cholangiopathy of infancy. Even after successful Kasai portoenterostomy (KPE), progressive liver fibrosis ultimately dictates long-term outcomes. The "microbiome-gut-liver axis" has fundamentally reshaped our understanding of liver disease pathogenesis, yet critical questions persist regarding how Kasai surgery reconfigures this axis and whether these changes actively contribute to fibrogenesis. This review traces a mechanistic cascade from anatomical remodeling through dysbiosis, metabolic disruption, immune dysregulation, and ultimately liver fibrosis. We examine how Kasai surgery physically reprograms the gut ecosystem through altered biliary-enteric continuity and bile acid circulation; how microbial metabolites-particularly secondary bile acids and short-chain fatty acids-orchestrate hepatic stellate cell behavior and shape the hepatic immune milieu; and how bacterial translocation sustains inflammation through Toll-like receptor signaling. Recent evidence challenging the primacy of TLR4 in long-term progression instead implicates TLR7 as a potential driver, while acknowledging its complex, context-dependent role that may involve both pro-fibrotic and counter-regulatory functions. Building on this foundation, we critically assess emerging intervention strategies-including probiotics, postbiotics, phage therapy, and personalized approaches-weighing translational potential against current evidence gaps and safety considerations. We propose that post-Kasai alterations in the bile acid pool may drive fibrogenesis through synergistic engagement of FXR and TLR pathways (including TLR4 and TLR7), and outline a stratified, dynamic intervention framework for precision microbiome management grounded in multi-omics integration and longitudinal cohort studies. By synthesizing current knowledge while identifying key uncertainties, this review aims to inform both mechanistic investigation and the development of microbiome-targeted adjunctive therapies for BA.