Berberine in Inflammatory Bowel Disease: Integrative Regulation of the Microbiota-Immune-Barrier Axis

Inflammatory bowel disease (IBD) is a chronic relapsing disorder associated with dysregulated interactions among the gut microbiota, mucosal immunity, and the intestinal barrier. Although current treatments have improved disease control, incomplete response, adverse effects, and relapse remain common. Berberine, a natural isoquinoline alkaloid, has gained attention as a multitarget compound with potential relevance to IBD. This narrative review summarizes evidence published up to March 2026 on the pharmacological basis, delivery optimization, clinical translation, and microbiota-immune-barrier axis regulation of berberine in IBD. Current evidence suggests that berberine may reshape gut microbial communities, regulate mucosal immune responses, and support epithelial barrier repair, thereby contributing to the restoration of intestinal homeostasis. Emerging formulation strategies, particularly microbiota-responsive and intestine-targeted delivery systems, may improve local exposure and strengthen its therapeutic potential. However, the current evidence is still dominated by preclinical studies. Clinical data remain limited, and the causal links among microbial remodeling, immune modulation, and barrier restoration are not yet fully defined. Future work should prioritize mechanistic validation, clinically relevant delivery design, and well-controlled clinical trials to clarify the role of berberine in personalized IBD management.