Diallyl disulfide attenuates DSS-induced colonic fibrosis in mice by modulating gut microbiota and Nrf2 signaling

The use of natural medicines as adjuvant therapies for fibrotic diseases has recently garnered significant attention. Diallyl disulfide (DADS), a bioactive sulfur compound from garlic, exhibits antioxidant, anti-inflammatory, and immunomodulatory effects, but its impact on colitis-associated intestinal fibrosis is unknown.

We administered DADS (80 mg/kg orally) to mice with dextran sulfate sodium (DSS)-induced chronic colitis-associated intestinal fibrosis and assessed clinical parameters, histopathological, immunohistochemistry, 16S rDNA—based gut microbiota profiling, and Mendelian randomization analysis.

DADS treatment ameliorated weight loss, disease activity index (DAI), colon shortening and histological damage, and reduced inflammatory infiltration and collagen deposition. Mechanistically, DADS activated the Nrf2 antioxidant pathway, inhibited TGF-β1/Smad3 fibrogenic signaling, and favorably altered gut microbial diversity and composition.

By engaging Nrf2, suppressing TGF-β1/Smad3 and modulating the gut microbiota, DADS attenuates colitis-associated intestinal fibrosis, highlight its potential as novel anti-fibrotic adjuvant.