Polysaccharides of Atractylodes Macrocephala Koidz effectively improve the EpCAM+/- genotype-related inflammatory bowel diseases via modulating gut microbiota.

The diminished EpCAM increases the susceptibility to inflammatory bowel disease (IBD). PAMK (polysaccharides of Atractylodes macrocephala Koidz) demonstrates the promotion for the intestinal health. To study the efficacy and mechanism of PAMK on mitigating IBD related to the downregulated EpCAM, it was administrated to the dextran sulfate sodium (DSS)-treated both WT and EpCAM+/- mice. DSS caused more pronounced damage to the mucosal muscular layer in the EpCAM+/- mice, increased the activity of MAPKs and upregulated the MMPs and inflammatory cytokines, but downregulated the tight junction-related proteins, STAT1, STAT6, and IRF1 in colonic tissues of the heterozygotes compared to the WT mice. After treatment with PAMK, colonic inflammation was effectively ameliorated in the DSS-induced both WT and heterozygous mice, with significant increased colon length, decreased inflammatory cells infiltration in the colonic mucosa and lamina propria, repaired colonic epithelial tight junctions, decreased activities of MAPKs and levels of MMPs, and PAMK administration promoted the reactivation of JAK-STAT-IRF1 pathway in the DSS-treated heterozygotes. Furthermore, PAMK altered the intestinal microbiota in the DSS-induced both WT and heterozygous mice, increasing the Akkermansiaceae particularly. In conclusion, PAMK could improve the colonic inflammation in not only WT mice but also EpCAM+/- mice via modulating the gut microbiota.