Atractylodes macrocephala Koidz polysaccharide improves glycolipid metabolism disorders through activation of aryl hydrocarbon receptor by gut flora-produced tryptophan metabolites

Polysaccharides are known to confer protection against glycolipid metabolism disorders (GMD) by regulating intestinal flora. In this study, a heterogeneous acidic heteropolysaccharide with high molecular weight mainly composed of fructose was isolated from Atractylodes macrocephala Koidz (AMP). Supplementation with AMP was shown to improve diet-induced GMD in a rat model, including decreasing the levels of serum triglycerides, total cholesterol, and glucose, and improving hepatic lipidosis and islet cells morphologies. AMP-treated rats also exhibited modified intestinal flora with enrichments of intestinal Lactobacillus and Rothia species, which was accompanied by increased tryptophan metabolites such as indole-3-propionic acid, indole, tryptamine, and tryptophol. These metabolites promote the expression of intestinal aryl hydrocarbon receptor (AhR) in nuclear fractions. AhR activation increased the expression levels of IL-22 and GLP-1 proteins and mRNA. IL-22 reduced systemic LPS by upregulating the expression of tight junction proteins, antimicrobial peptides, and mucin to ameliorate intestinal barrier function, and activated the hepatic IL-22R/Stat3/Acox1 signaling pathway to improve lipid metabolism. GLP-1 activated the pancreatic GLP-1R/p-CREB signaling pathway to ameliorate β-cell injury and improve insulin resistance. Therefore, the intestinal microbial-tryptophan metabolism-AhR pathway was deduced to be a mechanism by which this polysaccharide improves GMD.