Oudemansiella raphanipes polysaccharide alleviates DSS-induced colitis associated with gut microbiota and ZBP1-associated PANoptosis.

BACKGROUND

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with limited preventive options. The edible mushroom Oudemansiella raphanipes produces polysaccharides with reported bioactivity, but the effects of its purified fraction Oudemansiella raphanipes polysaccharide (UAE-ORP) on colitis remain unknown.

PURPOSE AND

METHODS

UAE-ORP was evaluated in mice with sodium dextran sulphate (DSS)-induced colitis using metagenomic and metabolomic analysis, as well as histological, ELISA and Western blot analysis of intestinal barrier function, ZBP1-associated PANoptosis-related proteins, and FFAR2/FFAR3 expression.

RESULTS

UAE-ORP alleviated DSS-induced colonic injury, reducing the DAI scores to 1.7 ± 0.3-2.7 ± 0.5 across treatment groups and restoring colon length to 6.2 ± 0.9-8.2 ± 0.8 cm across doses. UAE-ORP was associated with attenuated ZBP1-associated PANoptosis-related protein expression, increased Lachnospiraceae abundance, and restored acetic acid and 3,4-dihydroxyphthalate levels. UAE-ORP also restored the protein expression levels of FFAR2 and FFAR3. Correlation analysis suggested a potential association between Lachnospiraceae-related metabolites and FFAR2/FFAR3 signaling.

CONCLUSION

UAE-ORP alleviates DSS-induced colitis in mice. The protective effects coincide with altered gut microbiota composition, elevated microbial metabolites, restored FFAR2/FFAR3 expression, and concomitant changes in ZBP1-associated PANoptosis-related protein. These observations identify several candidate pathways warranting further investigation and provide preliminary mechanistic context for the anti-colitic activity of this mushroom polysaccharide.