Zanthoxylum bungeanum essential oil alleviates DSS-induced ulcerative colitis in mice by modulating gut microbiota-dependent AhR/Nrf2 signaling.

Supplementing healthy phytochemicals in the diet is considered a beneficial alternative to immunomodulatory drugs. Zanthoxylum bungeanum (Sichuan pepper) is one of China's traditional crops that serve both as food and medicine. The regulatory effect of Zanthoxylum bungeanum essential oil (ZBO) on dextran sulphate sodium (DSS)-induced UC in mice was conducted in our study. ZBO significantly ameliorated UC symptoms in mice, including suppression of pro-inflammatory mediators such as IL-6, IL-1β, TNF-α, and CCL20, elevation of anti-inflammatory cytokine levels, and upregulation of tight junction protein expression. Through 16S rRNA sequencing and KEGG enrichment analysis, the interaction between ZBO's regulatory effect on UC and gut microbiota modulation was further investigated. We found that the beneficial bacteria such as Verrucomicrobiota, Lachnospiraceae, Akkermansiaceae, and Alistipes_A were up-regulated and the proliferation of harmful bacteria including Desulfobacterota_I, Proteobacteria, Enterobacteriaceae_A, Escherichia, and Bacteroides_H. were down-regulated by ZBO. These microbial groups exhibited significant correlations with inflammatory mediators and mucosal proteins. Notably, KEGG data suggested ZBO may exert its anti-UC mechanism by regulating intestinal tryptophan metabolism and the peroxisome pathway. Meanwhile, the downstream of tryptophan metabolism and the peroxisome pathway, AhR/Nrf2 signals was activated by ZBO in this study. Overall, these results demonstrated that ZBO ameliorates colitis by modulating the gut microbiota-dependent AhR/Nrf2 signaling pathway, highlighting its potential as a phytochemical for UC treatment and suggesting its possible application in disorders associated with gut microbiota dysbiosis.