Lily polysaccharides alleviate colitis through the microbiota/N8AS/cGAS-STING signaling axis

With the rising incidence of IBD and limitations of current therapies, novel strategies are urgently needed. Recent studies have highlighted natural products in colitis treatment. Here, we investigated the therapeutic effects and mechanisms of lily polysaccharides (LP) in DSS-induced ulcerative colitis (UC). LP supplementation, alone or combined with N8-acetylspermidine (N8AS), alleviated weight loss and intestinal inflammation, restored microbial homeostasis, and increased beneficial bacteria like Bacteroidetes. LP significantly elevated N8AS levels, and exogenous N8AS also ameliorated UC symptoms. Mechanistically, LP and N8AS inhibited the cGAS–STING signaling pathway, reduced pro-inflammatory cytokine production, and promoted intestinal barrier repair in vitro. These results suggest that LP exerts anti-colitic effects via modulation of the microbiota/N8AS/cGAS–STING axis. This study identifies LP as a promising natural therapeutic for UC by linking microbiota regulation, metabolic modulation, and immune signaling inhibition.