Division of Oral Biology, College of Dentistry, The Ohio State University, Columbus, Ohio 43210, USA.
Infect Immun. 2010 Apr;78(4):1509-19. doi: 10.1128/IAI.00862-09. Epub 2010 Feb 9.
The gastrointestinal tract is colonized by an enormous array of microbes that are known to have many beneficial effects on the host. Previous studies have indicated that stressor exposure can disrupt the stability of the intestinal microbiota, but the extent of these changes, as well as the effects on enteric infection, has not been well characterized. In order to examine the ability of stressors to induce changes in the gut microbiota, we exposed mice to a prolonged restraint stressor and then characterized microbial populations in the intestines using both traditional culture techniques and bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP). Exposure to the stressor led to an overgrowth of facultatively anaerobic microbiota while at the same time significantly reducing microbial richness and diversity in the ceca of stressed mice. Some of these effects could be explained by a stressor-induced reduction in the relative abundance of bacteria in the family Porphyromonadaceae. To determine whether these alterations would lead to increased pathogen colonization, stressed mice, as well as nonstressed controls, were challenged orally with the enteric murine pathogen Citrobacter rodentium. Exposure to the restraint stressor led to a significant increase in C. rodentium colonization over that in nonstressed control mice. The increased colonization was associated with increased tumor necrosis factor alpha (TNF-alpha) gene expression in colonic tissue. Together, these data demonstrate that a prolonged stressor can significantly change the composition of the intestinal microbiota and suggest that this disruption of the microbiota increases susceptibility to an enteric pathogen.
胃肠道定植着大量的微生物，这些微生物对宿主有许多有益的影响。先前的研究表明，应激源暴露会破坏肠道微生物群落的稳定性，但这些变化的程度以及对肠道感染的影响尚未得到很好的描述。为了研究应激源是否能诱导肠道微生物群落的变化，我们让小鼠暴露于长期的束缚应激源中，然后使用传统的培养技术和细菌标签编码 FLX 扩增子焦磷酸测序（bTEFAP）来描述肠道中的微生物种群。应激源的暴露导致兼性厌氧菌微生物群落过度生长，同时显著降低了应激小鼠盲肠中的微生物丰富度和多样性。这些影响中的一些可以通过应激源诱导的卟啉单胞菌科细菌相对丰度的降低来解释。为了确定这些改变是否会导致病原体定植增加，我们让应激小鼠和非应激对照小鼠经口感染肠道病原体柠檬酸杆菌 rodentium。暴露于束缚应激源导致柠檬酸杆菌 rodentium 在应激小鼠中的定植显著增加，超过了非应激对照小鼠。这种增加的定植与结肠组织中肿瘤坏死因子 alpha（TNF-alpha）基因表达的增加有关。总之，这些数据表明，长期的应激源可以显著改变肠道微生物群落的组成，并表明这种微生物群落的破坏增加了对肠道病原体的易感性。
