METS-Sleep: Sleep timing, gut microbiota and cardiometabolic risk across the Epidemiologic Transition

METS-Sleep：流行病学转变过程中的睡眠时间、肠道微生物群和心脏代谢风险

• 批准号: 10636640
• 负责人: Lara Ruth Dugas
• 金额: $ 60.85万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636640
• 关键词: Adopted; Adult; Affect; Africa; African; American; Animals; Behavior; Behavioral; Blood Pressure; Body Weight Changes; Cardiometabolic Disease; Chronic Disease; Circadian desynchrony; Country; Darkness; Data; Diet; Dietary Practices; Dietary intake; Economic Development; Employment; Enrollment; Environment; Environmental Exposure; Epidemiology; Exposure to; Fatty acid glycerol esters; Feces; Food; Geographic Locations; Geography; Ghana; Glycosylated hemoglobin A; Goals; Health; High Density Lipoproteins; High Fat Diet; Hour; Human; Hypertriglyceridemia; Income; Individual; Individual Differences; International; Jamaica; Jamaican; Life Style; Light; Measurement; Measures; Mediation; Mediator; Metabolic syndrome; Modernization; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outcome Assessment; Participant; Pathway interactions; Phase; Physical activity; Polysomnography; Population; Populations at Risk; Prediabetes syndrome; Predisposition; Prospective, cohort study; Recording of previous events; Research; Risk; Risk Factors; Role; Sample Size; Sampling; Schools; Seychelles; Site; Sleep; Sleep disturbances; Social Development; Societies; South Africa; Time; Urbanization; Variant; Weight Gain; Work; Wrist; Writing; actigraphy; blood pressure elevation; cardiometabolic risk; cardiometabolism; circadian pacemaker; circadian regulation; cohort; epidemiological model; experimental study; fasting glucose; fecal transplantation; feeding; gut dysbiosis; gut microbiota; humanized mouse; longitudinal design; low income country; microbiome; microbiota; mortality; obesity risk; prospective; sleep pattern; time use; waist circumference

PROJECT SUMMARY Late chronotype has been associated with gut dysbiosis and increased cardiometabolic (CM) risk, yet the causal mechanisms are unknown. Existing studies are limited by contradictory findings, small sample sizes, imprecise measurements of sleep and CM risk, as well as lack of detailed measures of dietary intake and other environmental exposures/mediators. The objective of this study is to compare sleep patterns, gut microbiota, lifestyle behaviors, and risk for CM disease in individuals from 5 distinct African-origin populations. The second objective is to humanize mice with gut microbiota from study participants identified by chronotype (early vs. late) in each of the 5 cohorts and challenge the mice to high fat feeding in order to confirm the transferability of the late chronotype impact on gut dysbiosis. The proposed study will investigate sleep timing associations with the gut microbiota and CM risk, including elevated waist circumference, elevated fasting glucose, hypertriglyceridemia, elevated blood pressure, and low HDL, in existing cohorts with significant lifestyle diversity (i.e., diet and physical activity), who have been followed prospectively since 2010. The associations identified will guide fecal microbiota transplant experiments in mice using stool from participants identified by chronotype, and exposed to a 20-week high fat diet challenge to confirm the associations between sleep timing, gut microbiota and CM risk factors. Participants are currently enrolled in METS-Microbiome (R01-DK111848), an ongoing prospective cohort study leveraging an existing cohort of five diverse, well-defined populations from the Modeling the Epidemiologic Transition Study (METS, R01-DK080763). METS is comprised of a cohort of 2,500 adults, living in 5 distinctly different environments: Ghana, South Africa, Jamaica, Seychelles and the US. Our preliminary data from the METS cohorts suggest that gut microbiota diversity is negatively related to CM risk and sleep disruption. In addition to yearly health measurements, including anthropometrics, blood pressure and CM risk measures, we propose to measure sleep timing using actigraphy in 1000 participants (N=200 from each site) currently enrolled in METS-Microbiome. We will use a causal mediation analysis to identify the direct and indirect effects of sleep timing on the gut microbiota. We will thus capitalize upon existing, extensively described cohorts of adults from geographically dispersed populations, resulting in significant variation in environmental covariates. The proposed study will substantially advance our understanding of sleep timing associations with the gut microbiota and CM risk, which is critical given modern 24/7 “on-demand” societies requiring both night and early morning work hours.

项目摘要 晚期晚期型与肠道营养不良和心脏代谢增加（CM）风险相关，但因果关系 机制是未知的。现有研究受到矛盾的发现，小样本量，暗示的限制 睡眠和CM风险的测量以及缺乏饮食摄入量和其他饮食摄入量的详细测量 环境暴露/调解人。这项研究的目的是比较睡眠模式，肠道菌群， 来自5个不同非洲异教徒种群的个体中CM疾病的生活方式行为和风险。第二个 目的是用Chronotype确定的研究参与者的肠道菌群人性化小鼠（早期与晚期） 在这5个队列中的每一个中，并向小鼠挑战高脂肪进食，以确认 晚期对肠道营养不良的影响晚期影响。拟议的研究将调查与 肠道菌群和CM风险，包括腰围升高，空腹葡萄糖升高， 在现有的人群中，高甘油三酸酯血症，血压升高和HDL低，生活方式多样性 （即饮食和体育锻炼），自2010年以来一直受到前瞻性遵守。 将使用Chronotype鉴定的参与者的粪便引导小鼠中的粪便菌群移植实验， 并面临20周的高脂饮食挑战，以确认睡眠时间，肠道的关联 微生物群和CM风险因素。参与者目前已入学Mets-Microbiome（R01-DK111848） 正在进行的前瞻性队列研究利用现有的五个潜水员，定义明确的人群 建模流行病学过渡研究（METS，R01-DK080763）。大都会由2500个队列组成 成年人生活在5种截然不同的环境中：加纳，南非，牙买加，塞舌尔和美国。我们的 来自大都会队列的初步数据表明，肠道微生物群的多样性与CM风险和 睡眠中断。除了年度健康测量外，包括人类学，血压和商业 风险测量，我们建议使用1000名参与者的行为图测量睡眠时间（每个站点n = 200） 目前正在参加Mets-Microbiome。我们将使用因果中介分析来确定直接和间接的 睡眠时间对肠道菌群的影响。因此，我们将利用现有的，广泛描述的人群 来自地理分散人群的成年人的成年人，导致环境协变量的显着差异。 拟议的研究将大大提高我们对睡眠时间关联与肠道的理解 微生物群和CM风险，鉴于现代的24/7“ on-demand”社会至关重要，需要夜晚 早上工作时间。