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

被引:383
作者
Sekirov, Inna [2 ]
Tam, Nicola M. [3 ]
Jogova, Maria
Robertson, Marilyn L.
Li, Yuling
Lupp, Claudia
Finlay, B. Brett [1 ,2 ,3 ]
机构
[1] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
[2] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z4, Canada
[3] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z4, Canada
关键词
D O I
10.1128/IAI.00319-08
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:4726 / 4736
页数:11
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