Host genetic variation affecting the microbiome in rhesus macaques

项目总结 越来越多的文献专注于将微生物群与人类疾病联系起来，包括 肥胖、II型糖尿病、心血管疾病、癌症和自闭症等精神疾病， 精神分裂症和抑郁症。虽然这些关联仍然相对较新，而且在很大程度上是相互关联的，但它 并没有阻止旨在操纵微生物群的治疗学的发展 努力治疗这些疾病。然而，围绕微生物组仍有许多未知之处。 从导致其构成的因素到个体间变异的性质和来源 微生物群和疾病之间的实际致病联系，特别是在人类中。这是一个复杂的问题 人与啮齿动物模型的生理和微生物群组成的差异以及普遍存在的 人类无法控制的环境影响。这项提案使用了1300只恒河猴 来自4个菌落，以调查胃肠道、口腔和鼻部微生物组的变异性。它将成为 动物之间存在的个体差异，并进一步发展恒河猴作为模型 用于人类微生物组研究。利用拥有全基因组序列的800只动物和500只动物 有完整外显子组序列的动物，我们还建议全基因组和全外显子组关联 微生物群落多样性和特定细菌类群测定方法的研究。然后可以使用这些数据来 补充和聚焦微生物组的人类遗传学研究。这不仅将加深我们对 影响微生物组组成的因素，但它也将有助于发展灵长类动物模型 测试疾病与微生物组的相关性，并测试治疗干预措施改变 微生物群。

PROJECT SUMMARY An increasing body of literature has focused on associating the microbiome with human diseases including obesity, type II diabetes, cardiovascular disease, cancers, and psychiatric disorders such as autism, schizophrenia, and depression. While these associations are still relatively nascent and largely correlative, it has not stopped the push towards development of therapeutics aimed at manipulating the microbiome in an effort to treat these disorders. There remain, however, a great deal of unknowns surrounding the microbiome ranging from the factors responsible for its composition to the nature and sources of inter-individual variability to the actual causative links between microbiome and disease, particularly in humans. This is complicated by differences in physiology and microbiome composition between humans and rodent models and the pervasive effects of the environment that cannot be controlled for in humans. This proposal uses 1300 rhesus macaques from 4 colonies to investigate variability in the gastrointestinal, oral, and nasal microbiome. It will characterize the inter-individual variability that exists across animals and further develop the rhesus macaque as a model for human microbiome studies. Leveraging 800 animals with whole genome sequence available and 500 animals with whole exome sequence available, we also propose genome-wide and exome-wide association studies on measures of microbiome diversity and specific bacterial taxa. This data can then be used to complement and focus human genetic studies of the microbiome. This will not only further our understanding of factors that affect microbiome composition, but it will also assist in the development of primate models for testing disease associations with the microbiome and for testing the ability of therapeutic interventions to alter the microbiome.