Glehnia littoralis polysaccharides alleviate lung and intestinal mucosal barrier damage in rats with ulcerative colitis via aryl hydrocarbon receptor activation.

This study aimed to investigate the regulatory effects of Glehnia littoralis polysaccharides (GLP) on lung and intestinal mucosal barriers in rats with ulcerative colitis (UC). The results demonstrated that GLP inhibited the levels of TNF-α, IL-6, and MPO in colon tissues, alleviated colonic pathological damage, and reduced the expression of TNF-α, IL-6, IL-1β, and MPO in lung tissues, thereby ameliorating lung injury secondary to intestinal inflammation. Further analysis revealed that GLP restored the integrity of lung and intestinal mucosal barriers by upregulating the expression of mucin, ZO-1, and Occludin. In addition, GLP modulated the gut microbiota composition and increased the levels of tryptophan metabolites, including indole-3-carboxaldehyde (IAId), indole-3-acetic acid (IAA), and 5-hydroxyindoleacetic acid (5-HIAA), thereby activating the aryl hydrocarbon receptor (AhR) to further promote mucosal barrier repair. In vitro experiments showed that GLP reduced the levels of TNF-α, IL-6, IL-1β, MDA, and ROS, while increasing SOD activity and the expression of ZO-1, Occludin, Claudin-1, AhR, and CYP1A1 in lipopolysaccharide (LPS)-induced human normal colonic epithelial cells (NCM460) and human bronchial epithelial cells (BEAS-2B). However, the epithelial barrier protective effects of GLP in cells were abolished following the addition of an AhR antagonist. Collectively, these findings suggest that GLP may restore lung and intestinal mucosal barrier damage in UC by activating the shared AhR signaling pathway in both the lung and intestine.