Heterophyllin B an Active Cyclopeptide Alleviates Dextran Sulfate Sodium‐Induced Colitis by Modulating Gut Microbiota and Repairing Intestinal Mucosal Barrier via AMPK Activation

Scope Advances in pathology broaden the perception of the intimate interaction between gut microbiota dysbiosis and the pathogenesis of ulcerative colitis (UC), but the potential modulating roles remain to be elucidated. Methods and results DSS‐induced colitis is used to investigate the effect of Heterophyllin B (HB), a typical active cyclopeptide extracted from Pseudostellaria heterophylla , on colitis and gut microbiota. Administration of HB substantially mitigates the symptoms of UC as evidenced by increasing body weight and colon length, as well as decreased macrophages infiltration in the colon. Meanwhile, HB significantly alleviates intestinal mucosal barrier dysfunction by reducing the production of inflammatory cytokines, while all the mentioned beneficial effects are significantly eliminated by co‐treatment with compound C, a selective AMPK inhibitor. In addition, 16S rDNA gene analyses and fecal microbiota transplantation also reveal that HB dramatically prevents against UC by reshaping intestinal dysbiosis, especially elevates the relative abundance of Akkermansia muciniphila . Conclusion These findings illustrate that HB prominently improves intestinal epithelial homeostasis via activating AMPK and ameliorates the colonic inflammation in a gut microbiota‐dependent manner, which provide evidence for microbial contribution to UC pathogenesis and suggesting a novel approach for colitis prevention.