Restoring gut microbiota homeostasis to ameliorate colitis via Huangqin decoction.

Abstract

BACKGROUND: Ulcerative colitis (UC) is an inflammatory gut disorder involving dysregulated host-microbiota interactions. Huangqin decoction (HQD) is an herbal formula with known anti-inflammatory and microbiota-modulating effects, but its protective mechanism in ulcerative colitis remains unclear. PURPOSE: To investigate whether HQD ameliorates colitis by rebalancing gut microbiota homeostasis and to elucidate the underlying immunological and regenerative mechanisms involved. METHODS: A DSS-induced colitis mouse model was used to evaluate the effects of HQD. Colitis severity and inflammation were evaluated by the clinical disease index, histological analysis, and cytokine levels, and the gut microbiota profiles were analyzed via metagenomic sequencing. We used mechanistic assays to evaluate the effects of specific bacterial strains on intestinal organoids and neutrophil NETosis. RESULTS: HQD significantly alleviated colitis symptoms and inflammation. It remodelled the gut microbiota, suppressing Desulfovibrionaceae while enriching Lachnospiraceae. This microbiota shift drove reduced NETosis and activated Wnt/β-catenin signaling to enhance intestinal stem cell (ISC) proliferation, thereby promoting mucosal repair. In organoid cultures, Lachnospiraceae promoted organoid growth, whereas Desulfovibrionaceae caused epithelial damage and, independently, triggered NETosis in immune contexts. Notably, administration of the Lachnospiraceae bacterium ameliorated colitis and increased colonic Wnt/β-catenin signaling, confirming its regenerative role. CONCLUSION: HQD ameliorates colitis by rebalancing the gut microbiota, thereby suppressing harmful inflammation and promoting epithelial regeneration. These findings provide mechanistic support for HQD as a microbiota-mediated therapeutic strategy in colitis.