Protective Effect of Egg Yolk Lipids against Dextran Sulfate Sodium‐Induced Colitis: The Key Role of Gut Microbiota and Short‐Chain Fatty Acids

Abstract Egg yolk lipids significantly alleviate dextran sulfate sodium (DSS)‐induced colitis by inhibiting NLRP3 inflammasome, reversing gut microbiota dysbiosis, and increasing short chain fatty acids (SCFAs) concentrations. However, the role of gut microbiota and the relationship between SCFAs and NLRP3 inflammasome are still unknown. Here, this study confirms that antibiotic treatment abolishes the protective effect of egg yolk lipids on DSS‐induced colonic inflammation, intestinal barrier damage, and lipopolysaccharide translocation. Fecal microbiota transplantation also supports that egg yolk lipids alleviate colitis in a gut microbiota‐dependent manner. Then, the study investigates the relationship between SCFAs and NLRP3 inflammasome, and finds that SCFAs significantly suppress colitis via inhibiting colonic NLRP3 inflammasome activation and proinflammatory cytokines secretions (interleukin, IL)‐1β and IL‐18, and combined treatment of SCFAs and MCC950 (NLRP3 inhibitor) shows a better activity against colitis and NLRP3 inflammasome activation. Together, these findings provide positive evidence for gut microbiorta‐SCFAs‐NLRP3 axis as a novel target involving in the therapy of inflammatory bowel disease.