Depletion of butyrate-producing Clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella

By Fabian Rivera-Chávez, Lillian F. Zhang, F. Faber, Christopher A. Lopez, M. Byndloss, Erin E. Olsan, Gege Xu, Eric M Velazquez, C. Lebrilla, Sebastian E. Winter and 1 more. Cell Host and Microbe, 2016

753 citations recorded by the source corpus.

The mammalian intestine is host to a microbial community that prevents pathogen expansion through unknown mechanisms, while antibiotic treatment can increase susceptibility to enteric pathogens. Here we show that streptomycin treatment depleted commensal, butyrate-producing Clostridia from the mouse intestinal lumen, leading to decreased butyrate levels, increased epithelial oxygenation and aerobic expansion of Salmonella enterica serovar Typhimurium. Epithelial hypoxia and Salmonella restriction could be restored by tributyrin treatment. Clostridia depletion and aerobic Salmonella expansion were also observed in the absence of streptomycin treatment in genetically resistant mice, but proceeded with slower kinetics and required the presence of functional Salmonella type III secretion systems. The Salmonella cytochrome bd-II oxidase synergized with nitrate reductases to drive luminal expansion, and both were required for fecal-oral transmission. We conclude that Salmonella virulence factors and antibiotic treatment promote pathogen expansion through the same mechanism: depletion of butyrate-producing Clostridia to elevate epithelial oxygenation, allowing aerobic Salmonella growth.

Subfields: Endocrinology, Food Science, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8bef07e31bc014d9c396fc362878a47eb2aaad9a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology

1. G. Núñez
2. N. Inohara
3. M. Zeng

In Food Science

1. M. Zeng
2. G. Núñez
3. N. Inohara

In Molecular Biology

1. G. Núñez
2. M. Zeng
3. N. Inohara
4. T. Kanneganti
5. M. Lamkanfi

Citations in the corpus

• Microbiota-activated PPAR-γ-signaling inhibits dysbiotic Enterobacteriaceae expansion (2017, neutral): “Typhmurium strains (wild-type ATCC14028 resistant to nalidixic acid [IR715], IR715 invA spiB mutant, IR715 cyxA mutant or IR715 invA spiB cyxA mutant) (3) were routinely grown aerobically at 37°C in LB broth (BD Biosciences) or on LB plates.”
• Mechanisms of inflammation-driven bacterial dysbiosis in the gut (2016, positive): “luminal expansion of Salmonella via aerobic growth mediated by Salmonella type III cytochrome bd-II oxidase and synergized with nitrate reductases.(72) A previous study showed that aerobic respiration is required for commensal and pathogenic E.”
• Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases (2019, background): “These data are consistent with studies demonstrating that streptomycin-treated mices how relapse of gastroenteritis by Salmonella (51) as well as the expansion of potentially pathogenic E. coli (52).”
• Colonocyte metabolism shapes the gut microbiota (2018, background): “, lactate) and thus allows it to outcompete obligate anaerobic bacteria in the gut lumen (43, 74).”