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Infection and Immunity, October 2008, p. 4726-4736, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00319-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Antibiotic-Induced Perturbations of the Intestinal Microbiota Alter Host Susceptibility to Enteric Infection{triangledown}

Inna Sekirov,1,2 Nicola M. Tam,3,{dagger} Maria Jogova,1 Marilyn L. Robertson,1 Yuling Li,1 Claudia Lupp,1,{ddagger} and B. Brett Finlay1,2,3*

Michael Smith Laboratories,1 Department of Microbiology and Immunology,2 Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada3

Received 11 March 2008/ Returned for modification 10 April 2008/ Accepted 28 July 2008

Intestinal microbiota comprises 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 in drinking water for 2 days, followed by oral infection with Salmonella enterica serovar Typhimurium. Alterations in microbiota composition and numbers were evaluated by fluorescent in situ hybridization, differential plating, and Sybr green staining. Antibiotics had a dose-dependent effect on intestinal microbiota composition. The chosen antibiotic regimen did not significantly alter the total numbers of intestinal bacteria but altered the microbiota composition. Greater preinfection perturbations in the microbiota resulted in increased mouse susceptibility to Salmonella serovar Typhimurium intestinal colonization, greater postinfection 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 Salmonella serovar Typhimurium infection, demonstrating the importance of a healthy microbiota in host response to enteric pathogens.

* Corresponding author. Mailing address: #301-2185 East Mall, Michael Smith Building, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Phone: (604) 822-2210. Fax: (604) 822-9830. E-mail: bfinlay{at}interchange.ubc.ca

{triangledown} Published ahead of print on 4 August 2008.

Editor: B. A. McCormick

{dagger} Present address: Life Sciences Centre, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

{ddagger} Present address: Nature Publishing Group, The Macmillan Building, 4 Crinan Street, London N1 9XW, United Kingdom.

Infection and Immunity, October 2008, p. 4726-4736, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00319-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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