Contribution of bacterial and host factors to pathogen “blooming” in a gnotobiotic mouse model forSalmonella entericaserovar Typhimurium-induced enterocolitis

Abstract

AbstractInflammation has a pronounced impact on the intestinal ecosystem by driving an expansion of facultative anaerobic bacteria at the cost of obligate anaerobic microbiota. This pathogen “blooming” is also a hallmark of entericSalmonellaenterica serovar Typhimurium (S. Tm) infection. Here, we analyzed the contribution of bacterial and host factors toS. Tm “blooming” in a gnotobiotic mouse model forS.Tm-induced enterocolitis. Mice colonized with the Oligo-Mouse-Microbiota (OMM12), a minimal bacterial community, develop fulminant colitis by day 4 after oral infection with wild typeS. Tm but not with an avirulent mutant. Inflammation leads to pronounced reduction in overall intestinal bacterial loads, distinct microbial community shifts and pathogen blooming (relative abundance >50%).S.Tm mutants attenuated in inducing gut inflammation generally elicit less pronounced microbiota shifts and reduction in total bacterial loads. In contrast,S.Tm mutants in nitrate respiration, salmochelin production and ethanolamine utilization induced strong inflammation andS. Tm “blooming”. Therefore, individualSalmonella-specific inflammation-fitness factors seem to be of minor importance for competition against this minimal microbiota in the inflamed gut. Finally, we show that antibody-mediated neutrophil depletion normalized gut microbiota loads but not intestinal inflammation or microbiota shifts. This suggests that neutrophils equally reduce pathogen and commensal bacterial loads in the inflamed gut.