Microbiota-derived indole metabolites from Polygonatum cyrtonema polysaccharides fermentation alleviate colitis via Bifidobacterium pseudolongum and PPARγ activation.

Dietary polysaccharides can be transformed by gut microbiota into bioactive metabolites, yet the chemical identity and mechanisms of such products remain poorly defined. Here, we characterized the microbial fermentation products of Polygonatum cyrtonema polysaccharides (PCP) and evaluated their anti-colitic effects. Targeted LC-MS/MS revealed that PCP microbial fermentation products are enriched in tryptophan-derived indoles, particularly 5-hydroxytryptamine (29.21 ± 1.98 ng g-1), indole-3-lactic acid (1.53 ± 0.12 μg g-1), and indole-3-acetic acid (0.18 ± 0.02 μg g-1), along with free monosaccharides indicative of PCP degradation. In DSS-induced colitic mice, these products alleviated symptoms, restored barrier integrity, and enriched Bifidobacterium pseudolongum. Notably, administration of these products increased colonic 5-hydroxyindoleacetic acid (5-HIAA) levels (P < 0.001), consistent with conversion of exogenous 5-HT. The products also activated PPARγ signaling, an effect supported by molecular docking. Mono-colonization with B. pseudolongum recapitulated protection and elevated indole levels. These findings suggest a B. pseudolongum-indole-PPARγ axis as a candidate pathway mediating the benefits of PCP microbial fermentation products, supporting their development as functional food ingredients for gut health.