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.

项目概要 晚睡眠型与肠道菌群失调和心脏代谢 (CM) 风险增加有关，但其因果关系 机制尚不清楚。现有研究受到相互矛盾的发现、样本量小、不精确的限制 睡眠和 CM 风险的测量，以及缺乏饮食摄入和其他详细测量 环境暴露/介质。这项研究的目的是比较睡眠模式、肠道微生物群、 来自 5 个不同非洲裔人群的个体的生活方式、行为和 CM 疾病风险。第二个 目标是使小鼠人性化，其肠道微生物群来自按时间型（早期与晚期）确定的研究参与者 在 5 个队列中的每一个组中，对小鼠进行高脂肪喂养挑战，以确认 晚期时钟型对肠道菌群失调的影响。拟议的研究将调查睡眠时间与 肠道微生物群和 CM 风险，包括腰围升高、空腹血糖升高、 在具有显着生活方式多样性的现有人群中存在高甘油三酯血症、血压升高和低 HDL （即饮食和身体活动），自 2010 年以来一直对这些人进行前瞻性跟踪。这些协会确定 将使用按时间型识别的参与者的粪便指导小鼠的粪便微生物群移植实验， 并接受为期 20 周的高脂肪饮食挑战，以确认睡眠时间、肠道 微生物群和 CM 危险因素。参与者目前已注册 METS-Microbiome (R01-DK111848)，这是一个 正在进行的前瞻性队列研究利用现有的五个不同的、明确定义的人群的队列 流行病学转变研究建模（METS，R01-DK080763）。 METS 由 2,500 人组成 成年人，生活在 5 个截然不同的环境中：加纳、南非、牙买加、塞舌尔和美国。我们的 METS 队列的初步数据表明，肠道微生物群多样性与 CM 风险呈负相关， 睡眠中断。除了每年的健康测量，包括人体测量、血压和 CM 风险测量，我们建议使用体动记录仪测量 1000 名参与者的睡眠时间（每个站点 N=200） 目前就读于 METS-Microbiome。我们将使用因果中介分析来识别直接和间接的 睡眠时间对肠道微生物群的影响。因此，我们将利用现有的、广泛描述的群体 来自地理上分散的人群的成年人，导致环境协变量的显着变化。 拟议的研究将极大地增进我们对睡眠时间与肠道关联的理解 微生物群和 CM 风险，鉴于现代 24/7“按需”社会需要夜间和早起，这一点至关重要 早上的工作时间。