Berberine Alleviates Shigella-Induced Dysentery by Regulating Intestinal Barrier and Inflammatory Responses

Berberine (BBR), an isoquinoline alkaloid, has a long history of clinical use in treating dysentery. However, its precise mechanism has not been fully elucidated. This study aimed to investigate the intestinal protective mechanisms of BBR against <i>Shigella flexneri</i> (<i>S. flexneri</i>)-induced dysentery in mice. We found that BBR significantly upregulated the intestinal barrier proteins ZO-1, occludin, and E-cadherin, enhancing intestinal mucosal integrity to inhibit <i>S. flexneri</i> invasion. Moreover, BBR effectively attenuated M1 macrophage polarization and restored the Th1/Th17/Treg balance to reduce inflammatory injury upon <i>S. flexneri</i> infection. Specifically, BBR reduced both the populations of Th1 and Th17 cells and their production of inflammatory cytokines IFN-γ and IL-17A. Concurrently, it enhanced Treg cell populations and the secretion of anti-inflammatory cytokines IL-10 and TGF-β1. Additionally, the intestinal protective effect of BBR was further augmented by an increase in secretory IgA (sIgA). Collectively, our findings demonstrate that BBR protects against <i>S. flexneri</i>-induced dysentery by enhancing the intestinal barrier and inflammatory responses, providing support for its clinical use.