Faecalibaculum rodentium- derived quinic acid- mediated Treg differentiation drives the attenuation intestinal inflammation by Agrimoniae Herba polysaccharides.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory intestinal disorder characterized by gut dysbiosis, but effective strategies are currently limited. Here, we demonstrated that Agrimoniae Herba Polysaccharides (AHP), the key active components of a herb widely used for intestinal inflammation in East Asia countries, significantly reversed colitis-related phenotypes in a gut microbiota dependent, as antibiotic treatment abolished its therapeutic effect, while gut microbes from AHP-treated mice reproduced the anti-inflammatory effect. Bacterial 16S rRNA sequencing analysis showed AHP greatly reshaped the overall structure of microbiota, especially boosting colonization of Faecalibaculum rodentium (F. rodentium), which led to a significant alleviation of intestinal inflammation, accompanied by the promotion of CD4+ T cell differentiation toward Treg. Additionally, we identified quinic acid as a key metabolite of F. rodentium enriched by AHP treatment, and found that it induced the differentiation of naïve CD4+T cells sorted from UC patients into Treg cells in vitro, which correlated with the enhancement of TAZ/Foxp3 acetylation axis. Collectively, our results show that AHP exerts the beneficial effects in the treatment of UC by acting as a prebiotic to enrich the commensal bacterium F. rodentium, and offer a novel microbiota-dependent strategy for inflammatory bowel disease.