Sulforaphane attenuates DSS-induced ulcerative colitis via the Nrf2/STAT3 signaling pathway and gut microbiota modulation.

Nrf2 expression was reduced and STAT3 expression was elevated in the colonic mucosa of UC patients compared to healthy controls.

• Data derived from GEO database analysis comparing UC patients to healthy controls.
• Both differences were statistically significant at P < 0.01.
• This pattern suggests opposing roles for Nrf2 and STAT3 in UC pathology.

Nrf2 siRNA transfection abolished the protective effects of SFN in DSS-induced Caco-2 cells.

• Experiments conducted in a DSS-induced Caco-2 cell model of ulcerative colitis.
• Nrf2 knockdown via siRNA transfection eliminated SFN's ability to enhance Nrf2 and tight junction protein expression.
• Nrf2 knockdown also abolished SFN's suppression of inflammatory factors.
• Nrf2 knockdown eliminated SFN's reduction of the phosphorylated-STAT3/STAT3 ratio, linking Nrf2 to STAT3 regulation.

SFN alleviated colitic symptoms in wild-type DSS-induced colitis mice.

• Protective effects included attenuation of weight loss, colon edema, and colon shortening.
• SFN reduced inflammatory cell infiltration in wild-type mice.
• SFN reduced levels of inflammatory cytokines in wild-type colitis mice.
• SFN enhanced tight junction protein expression in wild-type mice with colitis.

The protective effects of SFN against DSS-induced colitis were largely abolished in Nrf2 knockout mice.

• Nrf2 knockout mice were used to confirm the necessity of Nrf2 for SFN's anti-colitic effects.
• Loss of Nrf2 eliminated SFN-mediated reductions in inflammatory cytokines and improvements in tight junction protein expression.
• Results confirm Nrf2 as a key mediator of SFN's protective action in vivo.

SFN reduced gut microbial diversity and altered bacterial abundance in Nrf2 knockout colitis mice.

• In Nrf2 knockout colitis mice specifically, SFN reduced gut microbial diversity.
• SFN decreased the relative abundance of Firmicutes at the phylum level in Nrf2 knockout mice.
• At the genus level, SFN decreased relative abundance of Muribaculaceae and Lachnospiraceae_NK4A136 in Nrf2 knockout mice.
• These microbiota changes occurred in the absence of Nrf2, suggesting Nrf2 normally mediates beneficial microbiota modulation by SFN.