Abstract

Ulcerative colitis (UC) involves chronic intestinal inflammation, epithelial barrier disruption, and microbial dysbiosis. Theabrownin (TB), a major bioactive compound derived from Pu-erh tea, has demonstrated anti-inflammatory properties, yet its role in intestinal barrier protection and underlying mechanisms remain unclear. In this study, TB (1 g per kg BW) was administered to dextran sulfate sodium salt (DSS)-induced colitis mice, leading to a marked alleviation in body weight loss and colon injury. TB significantly enhanced goblet cell function and mucus layer integrity, thereby supporting microbial homeostasis and epithelial defense. 16S rDNA sequencing revealed that TB restored microbial balance by enriching Prevotellaceae_UCG-001 while suppressing Eubacterium and Parasutterella. Mechanistically, TB upregulated ST6GalNAc6, reduced sialyl-Tn (STn) expression, and normalized MUC2 sialylation; inhibition of ST6GalNAc6 with 3Fax-Neu5Ac abrogated these protective effects. Collectively, these findings demonstrate that TB enhances intestinal barrier integrity and microbiota balance through modulation of the ST6GalNAc6-STn-MUC2 axis, highlighting its potential as a functional food ingredient for gut health management.