Dietary modulation of gut microbiome and host gene expression across human evolution and the emergence of modern human disease

人类进化和现代人类疾病出现过程中肠道微生物组和宿主基因表达的饮食调节

• 批准号: 9518889
• 负责人: Harinder Singh
• 金额: $ 92.04万
• 依托单位: J. CRAIG VENTER INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9518889
• 关键词: Adoption; Adult; Affect; African; Agriculture; Americas; C-reactive protein; Cardiovascular Diseases; Civilization; Data; Diet; Dietary Intervention; Disease; Disease model; Energy Metabolism; Evolution; Expression Profiling; Feces; Gene Expression; Genetic; Genetic Markers; Genome; Genomics; Glucose Metabolism Disorders; Glycosylated hemoglobin A; Goals; High Density Lipoproteins; Human; Human Genome; Immune; Incidence; Industrialization; Inflammation; Inflammatory; Intrinsic factor; Jamaica; Life Style; Light; Machine Learning; Mammals; Measures; Mediating; Metabolic; Metabolic Diseases; Metabolic Marker; Metabolic syndrome; Metagenomics; Microbe; Modeling; Modernization; Nutrient; Nutritional; Pattern; Population; Populations at Risk; Primates; Public Health; Resolution; Risk Factors; Role; Sampling; Societies; Structure; System; TNF gene; TNFRSF1A gene; Therapeutic Intervention; Tissue-Specific Gene Expression; Tissues; Triglycerides; Trinidad; Variant; Work; base; cohort; density; disease phenotype; disorder risk; fecal metabolome; glycemic control; gut microbiome; human disease; improved; learning strategy; lipid metabolism; metabolome; metabolomics; metagenome; microbial; microbial host; microbiome; microbiome composition; multiple omics; novel; nutrition related genetics; theories; transcriptome sequencing; transcriptomics; translational approach

Evidence suggests that lifestyle changes, concordant with the adoption of agriculture and industrialization, have impacted the emergence of the so-called diseases of modern civilization in humans (e.g. metabolic disorders, cardiovascular disease etc.). The incidence of these diseases in contemporary, industrialized populations is believed to be associated with a lack of adaptation of our genomes to the rapid dietary and lifestyle changes that occurred across human evolution. However the usefulness and resolution of this evolutionary model of disease are limited. Moreover, although the dietary and genetic markers of human evolution have been studied, we still lack understanding on how the microbiome, our second genome, has interacted with nutritional and host- genomic axes to confer increased disease risk in modern humans. Preliminary data by our group show that dietary shifts significantly modulate the gut microbiome and metabolome of wild primates, our closest evolutionary relatives. Additionally, we have identified gut microbiome markers only found in populations representing Paleolithic lifestyles (hunter-gatherers) and distinguishing them from traditional agriculturalists and industrialized populations. Thus, given 1) the potential role of diet in human evolution, 2) the critical impact of the gut microbiome on the nutritional and immune landscape of mammals, and 3) the existence of gut microbiome patterns exclusive of hunter-gatherers, we hypothesize that the emergence of metabolic disease in modern humans was significantly mediated by interactions between diet, the gut microbiome and the human genome across evolution. These issues are still unexplored. Thus, in Aim 1 of this proposal we will use a multi- OMIC approach (gut metabolomics, metagenomics and transcriptomics of the host colonic tissue) to identify metabolic and genetic markers that emerged and/or were lost when humans transitioned from hunter-gatherer to agricultural and industrialized lifestyles, and in humans affected by metabolic disease phenotypes. In Aim 2, we will use integrated meta-OMICs and network theory approaches to predict metabolic disease phenotypes, from hunter-gatherers to, populations in transition to agriculture to modern populations at risk. This system-level study will broaden our understanding of the extrinsic (environmental/nutritional) and intrinsic factors (genetic/metabolic) impacting the evolution of modern human disease. Additionally, the evolutionary approach proposed will shed light on potentially novel diet and microbe-based translational strategies to mitigate the incidence of metabolic disease in contemporary human populations.

有证据表明，生活方式的改变，与农业和工业化的采用相一致，具有 影响了所谓的现代文明疾病在人类中的出现(例如代谢紊乱， 心血管疾病等)。这些疾病在当代工业化人口中的发病率是 据信与我们的基因组缺乏适应快速的饮食和生活方式变化有关 发生在整个人类进化过程中。然而，这种疾病进化模型的有用性和解析性 是有限的。此外，尽管人类进化的饮食和遗传标记已经被研究过，但我们仍然 缺乏对微生物组，我们的第二个基因组，如何与营养和宿主相互作用的了解- 基因组轴赋予现代人更高的疾病风险。我们小组的初步数据显示， 饮食变化显著地调节了野生灵长类动物的肠道微生物群和代谢组，这是我们最接近的 进化中的亲戚。此外，我们已经确定了仅在人群中发现的肠道微生物组标记。 代表旧石器时代的生活方式(狩猎-采集者)，并将他们与传统的农学家和 工业化人口。因此，鉴于1)饮食在人类进化中的潜在作用，2)饮食的关键影响 肠道微生物群对哺乳动物的营养和免疫格局的影响；3)肠道的存在 不包括狩猎-采集者的微生物组模式，我们假设代谢性疾病在 现代人在很大程度上是通过饮食、肠道微生物群和人类之间的相互作用来调节的 整个进化过程的基因组。这些问题仍未得到探索。因此，在本提案的目标1中，我们将使用多个 组学方法(肠道代谢组学、宿主结肠组织的元基因组学和转录组学)来鉴定 当人类从狩猎-采集过渡时出现和/或丢失的代谢和遗传标记 农业和工业化的生活方式，以及受代谢性疾病表型影响的人类。在目标2中， 我们将使用集成的荟萃组学和网络理论方法来预测代谢性疾病的表型， 从狩猎-采集者到向农业转型的人口到处于危险之中的现代人口。这个系统级别 研究将扩大我们对外在(环境/营养)和内在因素的理解 (遗传/新陈代谢)影响现代人类疾病的进化。此外，进化论方法 建议将阐明潜在的新的饮食和基于微生物的翻译策略，以缓解 代谢性疾病在当代人类人群中的发病率。