Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection
Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection
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DOI：
10.1128/iai.00319-08
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发表时间：
2008-10-01
影响因子：
3.1
通讯作者：
Finlay, B. Brett
中科院分区：
文献类型：
--
作者：
Sekirov, Inna;Tam, Nicola M.;Finlay, B. Brett
肠道微生物群包括驻留在胃肠道中并且对正常宿主生理学至关重要的微生物群落。了解微生物群在宿主对入侵病原体的反应中的作用将进一步推进我们对宿主-微生物相互作用的认识。以鼠伤寒沙门氏菌为模型肠道病原菌，研究肠道菌群扰动对宿主感染易感性的影响。抗生素被用来扰乱肠道微生物群。C57 BL/6小鼠用临床相关剂量的链霉素和万古霉素在饮用水中处理2天，然后用鼠伤寒沙门氏菌口服感染。通过荧光原位杂交、差异平板培养和Sybr绿色染色评价微生物群组成和数量的变化。抗生素对肠道菌群组成具有剂量依赖性影响。所选择的抗生素方案没有显著改变肠道细菌的总数，但改变了微生物群的组成。更大的感染前微生物群扰动导致小鼠对鼠伤寒沙门氏菌肠道定植的易感性增加，更大的感染后微生物群改变，以及更严重的肠道病理学。这些结果表明，抗生素治疗改变了微生物群落的平衡，这使宿主易于感染鼠伤寒沙门氏菌，表明健康的微生物群在宿主对肠道病原体的反应中的重要性。
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.