Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota

Andrew W L Rogers; Lauren C Radlinski; Henry Nguyen; Connor R Tiffany; Thaynara Parente Carvalho; Hugo L P Masson; Michael L Goodson; Lalita Bechtold; Kohei Yamazaki; Megan J Liou; Brittany M Miller; Scott P Mahan; Briana M Young; Aurore M Demars; Sophie R Gretler; Anaïs B Larabi; Jee-Yon Lee; Derek J Bays; Renee M Tsolis; Andreas J Bäumler

doi:10.1016/j.chom.2024.07.025

Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota

Cell Host Microbe. 2024 Aug 20:S1931-3128(24)00284-1. doi: 10.1016/j.chom.2024.07.025. Online ahead of print.

Authors

Andrew W L Rogers¹, Lauren C Radlinski¹, Henry Nguyen¹, Connor R Tiffany¹, Thaynara Parente Carvalho¹, Hugo L P Masson¹, Michael L Goodson², Lalita Bechtold¹, Kohei Yamazaki³, Megan J Liou¹, Brittany M Miller¹, Scott P Mahan¹, Briana M Young¹, Aurore M Demars¹, Sophie R Gretler¹, Anaïs B Larabi¹, Jee-Yon Lee¹, Derek J Bays⁴, Renee M Tsolis¹, Andreas J Bäumler⁵

Affiliations

¹ Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
² Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, USA.
³ Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA; Laboratory of Veterinary Public Health, School of Veterinary Medicine, Kitasato University, Aomori, Japan.
⁴ Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of California at Davis, One Shields Avenue, Sacramento, CA 95817, USA.
⁵ Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA. Electronic address: ajbaumler@ucdavis.edu.

PMID: 39181125
DOI: 10.1016/j.chom.2024.07.025

Abstract

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota.

Keywords: Salmonella; colonization resistance; microbiota; mixed acid fermentation; short-chain fatty acids.