Novel Ophiopogon japonicus polysaccharide prevents chronic atrophic gastritis via gut microbiota/indole-3-acetic acid/AHR-CYP1A1-NF-κB axis

Ophiopogon japonicus (L. f.) Ker Gawl ., a traditional food ingredient in China with recognized benefits for gastric comfort, is commonly consumed in soups and herbal teas. Polysaccharides, the principal bioactive constituents, are promising candidates for dietary supplements and functional foods for the prevention of chronic atrophic gastritis (CAG). In this study, a polysaccharide with ameliorative effects against CAG was successfully isolated and designated as OJP-A. Its structure was elucidated, and the mechanisms underlying its protective effects against CAG were investigated using metabolomics and metagenomics analyses. The results showed that OJP-A comprises fructose and glucose and possesses a characteristic inulin-type structure. It mainly consists of a linear backbone of (1→2)-linked β-D-fructose units. The side chain contains a →2,4)-β-Glcp-(1→ residue attached to the fructose backbone through a (1→2) glycosidic linkage. Furthermore, the side chain is connected to other glucose residues through (1→4) and (1→2) linkages. OJP-A exerted therapeutic effects by modulating the gut microbiota, particularly by regulating Akkermansia muciniphila . This regulatory effect enhanced tryptophan metabolism and promoted the production of metabolites such as indole-3-acetic acid. These metabolites subsequently activated the aryl hydrocarbon receptor/cytochrome P450 family 1 subfamily A member 1 signaling axis, thereby suppressing the nuclear factor kappa-B-mediated inflammatory pathway and ultimately preventing and ameliorating CAG.