Sinensetin from citrus peel alleviates DSS-induced inflammation by regulating gut microbiota and serum metabolism in mice

Sinensetin is a polymethoxylated flavone, which is considered to be an important functional composition in citrus peels. In this study, the anti-inflammatory effect and potential mechanism of sinensetin were evaluated by multi-omics analysis in the dextran sulfate sodium (DSS)-induced colitis model. The results showed that sinensetin significantly inhibited inflammation and alleviated gut microbiota imbalance in the DSS-induced mice. Sinensetin supplementation increased the abundance of Faecalibaculum, Colidextribacter, Lachnospiraceae_NK4A136_group, norank_f_norank_Clostridia_UCG-014 and Christensenella, reduced abundance of Bacteroides, Escherichia-Shigella, Parasutterella and Clostridium_sensu_stricto_1. The metabolome of serum samples showed 117 differential metabolites were significantly altered by sinensetin supplementation in colitis mice, and 24 of these metabolites were involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway. KEGG predictions based on both gut microbiota and serum metabolites suggested that cysteine and methionine metabolism are mainly affected by sinensetin supplementation. These results indicate that sinensetin inhibit DSS-induced colitis by modulating gut microbiota and ameliorating serum metabolism.