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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Antiinflammatory effect; DSS-induced ulcerative colitis; Gut microbiota; Hydroxytyrosol; Inflammatory bowel disease; NLRP3 inflammasome.