Polysaccharides from Atractylodes macrocephala Koidz. Ameliorate ulcerative colitis via extensive modification of gut microbiota and host metabolism.

Turbulence of gut microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids is an important factor in the development of diseases. Many polysaccharides are effective on diseases including ulcerative colitis (UC), yet most studies investigating the mechanisms of polysaccharides mainly focused on their effects on gut microbiota composition and SCFAs, and other metabolites of gut microbiota are often neglected. Here, we examined the effects of polysaccharides from Atractylodes macrocephala Koidz. (AMP) on experimental UC induced by dextran sulfate sodium (DSS) and explored underlying mechanisms of AMP by 16S rDNA-based gut microbiota analysis and untargeted fecal and plasma metabolomics. In addition, a multiscale, multifactorial network was constructed to visualize the mechanisms of AMP. The results showed that AMP significantly increased body weight and ameliorated colonic injury in DSS treated mice. AMP also partly restored the perturbed gut microbiota composition induced by DSS. Untargeted fecal and plasma metabolomics showed that AMP can not only modulate the production of SCFAs by gut microbiota, but also the ability to digest food nutrients, metabolism of amino acids and bile acids, production of cadaverine and other metabolites by hosts and gut microbiota. The study demonstrated that, in addition to SCFAs, AMP can extensively modulate the metabolism of gut microbiota and hosts to achieve the therapeutic effects. This study adds new mechanisms of polysaccharides in treating diseases.