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Infect. Immun. doi:10.1128/IAI.00319-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection

Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z4; Department of Microbiology and Immunology, Department of Biochemistry and Molecular Biology, University of British Columbia

^* To whom correspondence should be addressed. Email: bfinlay{at}interchange.ubc.ca.

	Abstract

Intestinal microbiota comprise microbial communities that reside in the gastrointestinal tract and are critical to normal host physiology. Understanding the microbiota's role in host response to invading pathogens will further advance our knowledge of host-microbe interactions. Salmonella enterica serovar Typhimurium was used as a model enteric pathogen to investigate the effect of intestinal microbiota perturbation on host susceptibility to infection. Antibiotics were used to perturb the intestinal microbiota. C57BL/6 mice were treated with clinically relevant doses of streptomycin and vancomycin for 2 days in drinking water, followed by oral infection with Salmonella enterica serovar Typhimurium. Alterations in microbiota composition and numbers were evaluated by fluorescent in situ hybridization (FISH), differential plating, and SYBR green staining. Antibiotics had a dose-dependent effect on the intestinal microbiota composition. The chosen antibiotic regimen did not significantly alter the total numbers of intestinal bacteria, but altered the microbiota composition. Greater pre-infection perturbations in microbiota resulted in increased mouse susceptibility to S. Typhimurium intestinal colonization, greater post-infection alterations in the microbiota, and more severe intestinal pathology. These results suggest that antibiotic treatment alters the balance of the microbial community, which predisposes the host to S. Typhimurium infection, demonstrating the importance of a healthy microbiota in host response to enteric pathogens.

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