| Literature DB >> 30057174 |
Amanda Jacobson1, Lilian Lam1, Manohary Rajendram2, Fiona Tamburini3, Jared Honeycutt1, Trung Pham1, Will Van Treuren1, Kali Pruss1, Stephen Russell Stabler4, Kyler Lugo1, Donna M Bouley5, Jose G Vilches-Moure5, Mark Smith4, Justin L Sonnenburg6, Ami S Bhatt7, Kerwyn Casey Huang8, Denise Monack9.
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.Entities:
Keywords: Bacteroides; Salmonella; colonization resistance; intestine; intracellular pH; metabolism; microbiota; pathogen shedding; propionate; short-chain fatty acids
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Year: 2018 PMID： 30057174 PMCID： PMC6223613 DOI： 10.1016/j.chom.2018.07.002
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023