Abstract
The intestinal microbiota provides colonization resistance against pathogens, limiting pathogen expansion and transmission. These microbiota-mediated mechanisms were previously identified by observing loss of colonization resistance after antibiotic treatment or dietary changes, which severely disrupt microbiota communities. We identify a microbiota-mediated mechanism of colonization resistance against Salmonella enterica serovar Typhimurium (S. Typhimurium) by comparing high-complexity commensal communities with different levels of colonization resistance. Using inbred mouse strains with different infection dynamics and S. Typhimurium intestinal burdens, we demonstrate that Bacteroides species mediate colonization resistance against S. Typhimurium by producing the short-chain fatty acid propionate. Propionate directly inhibits pathogen growth in vitro by disrupting intracellular pH homeostasis, and chemically increasing intestinal propionate levels protects mice from S. Typhimurium. In addition, administering susceptible mice Bacteroides, but not a propionate-production mutant, confers resistance to S. Typhimurium. This work provides mechanistic understanding into the role of individualized microbial communities in host-to-host variability of pathogen transmission.
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•The composition of the host microbiota controls intestinal Salmonella infection•Bacteroides production of propionate mediates colonization resistance to Salmonella•Propionate limits Salmonella growth by disrupting intracellular pH homeostasis
Jacobson et al. show that the composition of the host microbiota controls intestinal expansion of the enteric pathogen S. Typhimurium. They demonstrate that Bacteroides spp. mediate colonization resistance to S. Typhimurium infection through production of the short-chain fatty acid propionate, which directly limits pathogen growth by disrupting intracellular pH homeostasis.