McKenna Philip, Hoffmann Christian, Minkah Nana, Aye Pyone Pyone, Lackner Andrew, Liu Zongzhi, Lozupone Catherine A, Hamady Micah, Knight Rob, Bushman Frederic D
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
PLoS Pathog. 2008 Feb 8;4(2):e20. doi: 10.1371/journal.ppat.0040020.
The vertebrate gut harbors a vast community of bacterial mutualists, the composition of which is modulated by the host immune system. Many gastrointestinal (GI) diseases are expected to be associated with disruptions of host-bacterial interactions, but relatively few comprehensive studies have been reported. We have used the rhesus macaque model to investigate forces shaping GI bacterial communities. We used DNA bar coding and pyrosequencing to characterize 141,000 sequences of 16S rRNA genes obtained from 100 uncultured GI bacterial samples, allowing quantitative analysis of community composition in health and disease. Microbial communities of macaques were distinct from those of mice and humans in both abundance and types of taxa present. The macaque communities differed among samples from intestinal mucosa, colonic contents, and stool, paralleling studies of humans. Communities also differed among animals, over time within individual animals, and between males and females. To investigate changes associated with disease, samples of colonic contents taken at necropsy were compared between healthy animals and animals with colitis and undergoing antibiotic therapy. Communities from diseased and healthy animals also differed significantly in composition. This work provides comprehensive data and improved methods for studying the role of commensal microbiota in macaque models of GI diseases and provides a model for the large-scale screening of the human gut microbiome.
脊椎动物的肠道中栖息着大量的共生细菌群落,其组成受宿主免疫系统的调节。许多胃肠道(GI)疾病预计与宿主 - 细菌相互作用的破坏有关,但相对较少有全面的研究报道。我们使用恒河猴模型来研究影响胃肠道细菌群落的因素。我们使用DNA条形码和焦磷酸测序来表征从100个未培养的胃肠道细菌样本中获得的141,000个16S rRNA基因序列,从而能够对健康和疾病状态下的群落组成进行定量分析。恒河猴的微生物群落在现存分类群的丰度和类型上均与小鼠和人类不同。与人类研究相似,恒河猴肠道黏膜、结肠内容物和粪便样本中的群落也存在差异。群落也因动物个体、个体动物随时间以及雄性和雌性之间的不同而有所差异。为了研究与疾病相关的变化,我们比较了健康动物和患有结肠炎并接受抗生素治疗的动物在尸检时采集的结肠内容物样本。患病动物和健康动物的群落组成也存在显著差异。这项工作为研究共生微生物群在恒河猴胃肠道疾病模型中的作用提供了全面的数据和改进的方法,并为大规模筛选人类肠道微生物组提供了一个模型。