Pectic polysaccharides from Mongolian medicinal Hypecoum leptocarpum: Structure and ulcerative colitis amelioration via gut microbiota and intestinal inflammation regulation.

Ulcerative colitis (UC) poses a global health burden due to its refractoriness. Our previous study demonstrated that Hypecoum leptocarpum (H. leptocarpum) crude polysaccharides mitigate UC-related intestinal inflammation. In this study, we extracted, purified, and characterized a pectic polysaccharide (HLP-4-2, 19.7 kDa) from H. leptocarpum, which contained homogalacturonan (HG) and rhamnogalacturonan-I (RG-I). Specifically, RG-I comprises a repeating disaccharide unit of 1,4-α-GalpA and 1,2-α-Rhap (with arabinogalactan branches), whereas HG has partially methyl-esterified GalA residues. In DSS-induced UC mice, HLP-4-2 alleviated disease symptoms in a dose-dependent manner, as evidenced by a reduced disease activity index (DAI), restored colon length, and decreased spleen index. Mechanistically, HLP-4-2 modulated gut microbiota by promoting growth of short-chain fatty acid (SCFA)-producing bacteria (e.g., Prevotella) and reducing abundance of pathogenic bacteria (e.g., Klebsiella). This microbial shift elevated SCFA levels (particularly propionic and isobutyric acids) and reduced isocaproic acid levels. These changes may, in turn, strengthen the intestinal barrier by enhancing mucin secretion, preserving goblet cells, and reducing inflammation via downregulating proinflammatory cytokines. Fecal microbiota transplantation (FMT) experiments confirmed that these microbial changes contributed to HLP-4-2's therapeutic effects. These findings endorse the traditional use of H. leptocarpum for inflammation and indicate HLP-4-2 as a potential treatment for ulcerative colitis.