Integrated Microbiome and Metabolomics Analysis Reveals That Ganoderma lucidum Triterpenoids Ameliorate Colitis...

Colitis is a global health challenge that severely impairs quality of life, necessitating effective dietary interventions. This study investigated the protective effects of Ganoderma lucidum triterpenoids (GLTs) on pathological symptoms, inflammatory responses, and gut microbiota dysbiosis in a dextran sulfate sodium (DSS)-induced murine model. Our results demonstrated that GLT intervention significantly attenuated the disease activity index (DAI), prevented colon shortening, and fortified gut barrier integrity through upregulating the transcription of tight junction proteins. GLT inhibited the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and bolstered antioxidant defenses (CAT) by controlling the TLR4/NF-κB pathway and upregulating the Nrf2 pathway. Furthermore, 16S rRNA sequencing and non-targeted metabolomics revealed that GLT reshaped the gut microbial landscape (enriching Enterorhabdus and Lachnospiraceae NK4A136 group) and reconfigured amino acid metabolism to restore colonic homeostasis. Collectively, these findings highlight the potential of GLT as a functional food ingredient to prevent colitis, potentially linked to the modulation of the microbiota-metabolite-immune interplay, offering a novel nutritional strategy for inflammatory bowel disease management.