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 Shigella flexneri (S. flexneri)-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 S. flexneri invasion. Moreover, BBR effectively attenuated M1 macrophage polarization and restored the Th1/Th17/Treg balance to reduce inflammatory injury upon S. flexneri 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 S. flexneri-induced dysentery by enhancing the intestinal barrier and inflammatory responses, providing support for its clinical use.

Berberine; Shigella infection; dysentery; inflammatory responses; intestinal barrier.