Host genetic variation affecting the microbiome in rhesus macaques

影响恒河猴微生物组的宿主遗传变异

• 批准号: 10448419
• 负责人: Eric J. Vallender
• 金额: $ 23.25万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10448419
• 关键词: 16S ribosomal RNA sequencing; Address; Affect; Animal Model; Animal Sources; Animals; Behavioral; Biological Models; Breeding; Cardiovascular Diseases; Communicable Diseases; Communities; Complement; Correlation Studies; Data; Development; Diet; Disease; Environment; Environmental Exposure; Etiology; Genetic; Genetic Variation; Genetic study; Genome; Goals; Grant; Habitats; Health; Human; Human Genetics; Human Microbiome; Immune Response Genes; Individual; Intervention; Knowledge; Link; Literature; Location; Macaca mulatta; Malignant Neoplasms; Measures; Mental Depression; Mental disorders; Metagenomics; Modeling; Nature; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Physiological; Physiological Processes; Physiology; Positioning Attribute; Primates; Procedures; Research; Resources; Rodent; Rodent Model; Role; Sample Size; Schizophrenia; Site; Source; Structure; Testing; Therapeutic; Therapeutic Intervention; autism spectrum disorder; base; dietary control; exome; gastrointestinal; genetic association; genome wide association study; genome-wide; gut microbiome; human disease; human model; improved; innovation; inter-individual variation; interest; microbial; microbial community; microbiome; microbiome alteration; microbiome composition; microbiome research; nasal microbiome; nasal swab; next generation sequencing; nonhuman primate; oral microbiome; primate development; stool sample; therapeutic development; translational study; whole genome

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.

项目概要 越来越多的文献关注微生物组与人类疾病的关联，包括 肥胖、二型糖尿病、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。虽然这些关联仍相对较新且在很大程度上具有相关性，但 并没有停止推动旨在操纵微生物组的疗法的发展 努力治疗这些疾病。然而，围绕微生物组仍然存在大量未知因素 从构成其组成的因素到个体间变异的性质和来源 微生物组与疾病之间的实际因果关系，特别是在人类中。这很复杂 人类和啮齿动物模型之间生理学和微生物组组成的差异以及普遍存在的 环境对人类的影响是无法控制的。该提案使用了1300只恒河猴 来自 4 个菌落，以研究胃肠道、口腔和鼻腔微生物组的变异性。它将表征 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 800 只拥有全基因组序列的动物和 500 只动物 具有完整外显子组序列的动物，我们还提出全基因组和全外显子组关联 微生物组多样性和特定细菌类群测量的研究。然后可以使用该数据 补充并集中人类微生物组遗传学研究。这不仅可以加深我们对 影响微生物组组成的因素，但它也将有助于灵长类动物模型的开发 测试疾病与微生物组的关联，并测试治疗干预措施改变的能力 微生物组。