Tremella fuciformis stem alleviates colitis by modulating gut microbiota and PI3K/AKT/NF‑κB pathway

This is the authors' abstract. We don't add key points for this paper.

The rising global prevalence of ulcerative colitis (UC) highlights an urgent need for safe and effective interventions. The Tremella fuciformis stem (TS), a major by-product of the edible fungus industry, is rich in polysaccharides and triterpenoids with known anti-inflammatory properties, yet its potential in UC management remains underexplored. This study evaluated the protective effects of TS water extract (TSW) against DSS-induced colitis in mice. TSW dose-dependently reduced the disease activity index, attenuated colonic histopathological damage, and enhanced antioxidant capacity by increasing T-AOC, SOD, CAT, GSH-PX, and POD activities while decreasing MDA levels. TSW also restored intestinal barrier integrity by upregulating ZO-1, Occludin, and MUC-2, and downregulating Claudin-2. Major bioactive constituents identified include 3-butene-1,2,3-tricarboxylic acid, dl-arginine, choline, kojic acid, and cinnamic acid. Network pharmacology predicted anti-UC targets, which were validated by in vivo experiments showing that TSW inhibited the phosphorylation of PI3K, AKT, and NF-κB p65, and reduced TNF-α and IL-1β expression. Notably, FMT showed that TSW-modulated microbiota could transfer therapeutic benefits. However, antibiotic depletion of gut microbiota abolished TSW efficacy. This confirmed a microbiota-dependent mechanism. Multi-omics integration revealed that TSW selectively enriched Bacteroides and Akkermansia , while reducing Blautia, unclassified_Lachnospiraceae , and Lachnospiraceae_NK4A136_group . Metabolomically, TSW upregulated l-tryptophan, kynurenic acid, and 5-hydroxyindoleacetate, and downregulated leukotriene C4 and 5(S)-HPETE. Proteomically, TSW downregulated Siah1a and Klf4, while restoring Serpina6. This work highlights the valorization potential of T. fuciformis processing by-products for the development of microbiota-targeted dietary strategies.