Contribution of bacterial and host factors to pathogen "blooming" in a gnotobiotic mouse model for Salmonella enterica serovar Typhimurium-induced enterocolitis.

Inflammation 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 enteric Salmonella enterica serovar Typhimurium ( S . Tm) infection. Here, we analyzed the contribution of bacterial and host factors to S . Tm "blooming" in a gnotobiotic mouse model for S . 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-type S . Tm but not with an avirulent mutant. Inflammation leads to a 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 and S . Tm "blooming." Therefore, individual Salmonella -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.