Title : Sulforaphane attenuates DSS-induced ulcerative colitis and secondary liver injury in mice by targeting gut microbiota and its metabolites
Abstract:
Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has demonstrated therapeutic potential in inflammatory diseases. In the present study, we investigated the protective effects and underlying mechanisms of SFN in Dextran Sulfate Sodium (DSS)-induced Ulcerative Colitis (UC) and its associated secondary liver injury. Our results showed that SFN markedly alleviated histopathological damage, suppressed the production of pro-inflammatory cytokines (TNF-α and IL-1β) in both colonic and hepatic tissues, improved liver function parameters, and enhanced the expression of intestinal tight junction proteins and Muc2 in DSS-treated mice.
Furthermore, 16S rRNA sequencing revealed that SFN profoundly reshaped the gut microbiota composition, reducing pathogenic taxa such as Romboutsia ilealis and Enterococcus faecalis, while enriching beneficial species including Akkermansia muciniphila. Metabolomic analyses demonstrated that SFN increased Short-Chain Fatty Acid (SCFA) levels and remodeled the Bile Acid (BA) profile, characterized by decreased sulfated BAs and increased secondary BAs. Mechanistically, SFN activated the SCFA receptor FFAR2 and bile acid receptors FXR and TGR5, thereby promoting M2 macrophage polarization and regulatory T cell expansion in colitic mice. In addition, SFN regulated enterohepatic bile acid circulation through the FXR-FGF15-SHP axis and activated Wnt/β-catenin signalling. Notably, these protective effects were largely abolished in Nrf2-deficient UC mice. In the absence of Nrf2, SFN reduced gut microbial diversity and decreased the relative abundance of Firmicutes at the phylum level, as well as Muribaculaceae and Lachnospiraceae_NK4A136 at the genus level.
Collectively, these findings demonstrate that oral administration of SFN alleviates UC and its secondary liver injury by modulating a coordinated “microbiota–metabolites–host receptor” axis.
