Colonic administration of baitouweng decoction alleviates ulcerative colitis via coordinated reprogramming of arginine and tryptophan metabolism.

BACKGROUND

Ulcerative colitis (UC) involves persistent colonic inflammation, loss of epithelial barrier integrity, and disturbed immune regulation. Although Baitouweng decoction (BTW) is widely used for intestinal inflammatory disorders, the effects and mechanisms of colon-targeted administration remain unclear.

PURPOSE: This study evaluated the effects of transendoscopic enteral tubing (TET)-mediated colonic BTW administration (CBTW) in dextran sulfate sodium (DSS) induced colitis and examined its association with arginine and tryptophan metabolism.

METHODS

CBTW efficacy was evaluated in DSS-induced colitis rats using integrated phenotypic, histological, multi-omics, and immune profiling approaches. Candidate metabolic pathways were mechanistically validated through pharmacological inhibition of arginase activity, IDO1, and AhR signaling using BEC hydrochloride, 1-methyl-L-tryptophan, and CH-223191, respectively, combined with downstream metabolite rescue by spermidine and kynurenine.

RESULTS

CBTW ameliorated DSS-induced colitis, reducing body-weight loss, DAI scores, colonic shortening, histopathological injury, mucus depletion, and barrier disruption. Multi-omics analyses revealed coordinated alterations in arginine and tryptophan metabolism. CBTW was associated with increased ARG2 expression, elevated ornithine and spermidine levels, and enhanced M2 macrophage-associated responses. It was also associated with increased kynurenine and kynurenic acid levels and enhanced AhR-related signaling, as indicated by CYP1A1 upregulation. These changes coincided with an improved Treg/Th17 balance, reduced inflammation, and enhanced epithelial barrier integrity. Pharmacological inhibition and metabolic rescue supported the functional involvement of the ARG2-associated arginine-spermidine axis and IDO1-kynurenine-AhR pathways.

CONCLUSIONS

CBTW alleviated DSS-induced colitis and coordinately modulated arginine and tryptophan metabolism, providing preclinical support for its further evaluation as a TET-delivered treatment for UC.