Hydroxytyrosol alleviates dextran sodium sulfate–induced colitis by inhibiting NLRP3 inflammasome activation and modulating gut microbiota in vivo

•Hydroxytyrosol ameliorated pathologic morphology and apoptosis and enhanced the antioxidant capacities of dextran sodium sulfate (DSS)–induced colitis in mice.•Hydroxytyrosol inhibited NLRP3 inflammasome activation in DSS-induced colitis in mice.•Hydroxytyrosol shifted the gut microbiota from more pathogens toward probiotics, and increased short-chain fatty acids, in DSS-induced colitis in mice.•The NLRP3 inflammasome plays a critical role in DSS-induced colitis, and thus can serve as a potential target for the development of novel therapeutics for inflammatory bowel disease. An increase in the global prevalence of inflammatory bowel disease has been reported in recent years. Although its pathogenesis has not been fully elucidated, inflammatory bowel disease is highly correlated with intestinal oxidative stress, immune disorders, overexpression of proinflammatory factors, and imbalance of gut microbiota. Hydroxytyrosol (HT), extracted from olive oil and leaves, exhibits significant antioxidant and antiinflammatory activities. Therefore, this study sought to evaluate whether the antiinflammatory effect of HT on dextran sodium sulfate (DSS)–induced ulcerative colitis in mice is regulated by targeting the NLRP3 inflammasome and gut microbiota. Colon pathologic morphology and apoptosis were found to be ameliorated in the DSS + HT group compared to the DSS group. Antioxidant capacity was higher in the DSS + HT group than in the DSS group (P < 0.01). HT suppressed expression levels of NLRP3, caspase-1, and ASC mRNA and downregulated interleukin-18 and interleukin-1β levels in the DSS group (P < 0.01). Furthermore, HT exerted a shift from pathogens to probiotics, and increased the levels of short-chain fatty acids (P < 0.01) in the DSS group. In summary, HT supplementation exerts antiinflammatory effects in DSS-induced ulcerative colitis by enhancing colonic antioxidant capacities, inhibiting NLRP3 inflammasome activation, and modulating gut microbiota in vivo.