Muribaculum intestinale restricts Salmonella Typhimurium colonization by converting succinate to propionate

Abstract Insufficient dietary fiber intake is associated with dysbiosis and compromised colonization resistance (CR) to enteric infections. However, a detailed understanding of the relationship between dietary fiber insufficiency and CR remains elusive. Our study aimed to delineate the impact of fiber deprivation on gut microbiome and CR in a murine model with Salmonella Typhimurium infection. Our findings indicate that dietary fiber deprivation resulted in impaired CR and depletion of commensal bacteria Muribaculaceae. By combining dietary switch, FMT, and genomic analysis, we identify Muribaculum intestinale as a candidate bacterium, capable of converting succinate into propionate. Oral administration of Muribaculum intestinale augmented CR to Salmonella Typhimurium, accompanied by succinate reduction and propionate elevation. Dietary supplementation of propionate, but not succinate, enhanced CR to Salmonella Typhimurium in mice consuming a fiber-free diet. Taken together, our research identified a crucial metabolic pathway encoded by gut microbiome underlying CR, providing an intervention strategy for combatting enteric infections among Western diet-consuming populations.