Atractylodes macrocephala Koidz polysaccharide ameliorates DSS‐induced colitis in mice by regulating the gut microbiota and tryptophan metabolism

Background and Purpose Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS‐induced colitis, and we aimed to investigate the underlying mechanisms in this study. Experimental Approach PAMK was used to treat DSS‐induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan‐metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic‐mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis. Key Results PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan‐metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance. Conclusion and Implications Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS‐induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.