THE MACAQUE GUT MICROBIOME IN HEALTH, LENTIVIRAL INFECTION AND IBD

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 脊椎动物的肠道里有一个巨大的细菌互助体群落，其组成受到宿主免疫系统的调节。许多胃肠道(GI)疾病被认为与宿主-细菌相互作用的中断有关，但相对较少的全面研究报道。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条码和焦磷酸测序对从100个未培养的GI细菌样本中获得的141,000个16S rRNA基因序列进行了表征，从而能够定量分析健康和疾病中的群落组成。猕猴的微生物群落与老鼠和人类的微生物群落在数量和种类上都不同。猕猴的群落在肠道粘膜、结肠内容物和大便方面的样本之间存在差异，这与对人类的研究相似。不同动物之间的群落也不同，随着时间的推移，个体动物内部以及雄性和雌性之间也不同。为了研究与疾病(艾滋病)相关的变化，对健康动物和患有结肠炎并接受抗生素治疗的动物进行了尸检时采集的结肠内容物样本的比较。患病动物和健康动物的群落在组成上也有很大差异。这项工作为研究共生微生物区系在胃肠道疾病猕猴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模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 (AIDS), 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.