Response of the Gut Microbiome and Circulating Metabolome to Diet Intervention in Young Children: Ancillary Study to the Keeping Ideal Cardiovascular Health Family Intervention Trial (KIDFIT)

幼儿肠道微生物组和循环代谢组对饮食干预的反应：保持理想心血管健康家庭干预试验 (KIDFIT) 的辅助研究

• 批准号: 10526398
• 负责人: Amanda K Marma
• 金额: $ 18.96万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10526398
• 关键词: 5 year old; Address; Adolescent; Adult; Age; Ancillary Study; Animal Experiments; Animal Model; Animals; Atherosclerosis; Beginning of Life; Bioinformatics; Biological Markers; Biology; Birth; Blood; Blood Pressure; Body fat; Body mass index; Branched-Chain Amino Acids; Cardiology; Cardiovascular Diseases; Cessation of life; Chemicals; Child; Childhood; Chronic Disease; Clinical Trials; Collection; Communities; Complement; Conduct Clinical Trials; Coronary Arteriosclerosis; Coronary heart disease; DASH diet; DNA; Data; Development; Diet; Dietary Intervention; Dietary Practices; Disease; Ensure; Environment; Epidemiologist; Epidemiology; Evaluation; Family health status; Fellowship; Foundations; Funding; Genes; Goals; Health; Health Promotion; Human; Intervention; Intervention Studies; Intervention Trial; K-Series Research Career Programs; Knowledge; Lead; Life; Link; Lipids; Measures; Mediation; Mentors; Mentorship; Metabolic; Metabolic Pathway; Metabolism; Methods; Modeling; Molecular; Molecular Biology; Mothers; National Heart, Lung, and Blood Institute; National Research Service Awards; Nursery Schools; Nutritional; Obesity; Obesity Epidemic; Outcome; Overnutrition; Overweight; Participant; Pathway Analysis; Pathway interactions; Pediatric Hospitals; Phenotype; Pregnancy; Preventive; Prevotella; Public Health; Recommendation; Research; Research Personnel; Resources; Risk; Sampling; School-Age Population; Scientist; Serum; Strategic vision; Stroke; Systems Biology; Testing; Time; Training; Transcript; Translating; Translational Research; Translations; Universities; Validation; Work; animal data; biological systems; blood lipid; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; career; clinical application; clinical training; clinically relevant; design; dietary; early childhood; experience; gut microbes; gut microbiome; high risk; insight; metabolic phenotype; metabolome; metabolomics; microbial; microbiome; multidisciplinary; novel; nutrition; obese mothers; obesity in children; obesity risk; offspring; overweight child; pediatric cardiologist; preservation; prevent; programs; response; skills; small molecule; translational research program; trial design; validation studies

PROJECT SUMMARY/ABSTRACT The majority of deaths from cardiovascular disease (CVD) in US adults ages 25-54 years are associated with suboptimal diet. While diet is an important target of CVD prevention efforts in adults, intervention on the childhood diet may be more effective. Animal data suggest that early-life diet has the unique potential to modulate biological systems and durably program a child’s biology for long-term health or disease. Yet, although NHLBI’s Strategic Vision Objective 1 prioritizes understanding how diet modulates biological systems such as the micro- biome and metabolome to sustain health, only limited animal and observational adult data exist. The objective of this application is to define the molecular effects of a dietary pattern intervention on the gut microbiome and circulating metabolome in young children. This objective will be attained through an ancillary study to a funded clinical trial that tests the effects of a 12-month Dietary Approaches to Stop Hypertension (DASH) diet interven- tion on adiposity and other CVH metrics (e.g., blood pressure, lipids) in 3- to 5-year old children (n=140). Using additional participant samples, deep phenotyping and advanced bioinformatics, the proposed work will address three specific aims. First, it will test the effect of the DASH diet intervention on the gut microbiome, including abundances of microbial taxa, communities, and metabolism-related genes and transcripts. Second, it will define the associations of diet and the gut microbiome with the circulating metabolome. Using targeted and nontargeted metabolomics approaches, blood metabolites, metabolite networks, and metabolic pathways will be evaluated. Finally, in an exploratory fashion, it will probe pathways linking the diet intervention with subsequent adiposity and CVH metrics, through the gut microbiome and serum metabolome. The expected outcome is a preliminary model of how the DASH diet alters the gut microbiome and circulating metabolome in young children, and how these alterations relate to short-term CVH outcomes. These pilot data can be validated in larger samples, and thereby contribute to eventual development of novel, targeted early-life dietary strategies to preserve ideal CVH. The proposed research will also be leveraged as a training platform for Amanda Marma Perak, MD, who aims to have an independent translational research program focused on understanding early-life determinants of CVH and developing strategies to preserve life-long CVH. A team of prominent scientists will provide mentorship in a rich research developmental environment at Northwestern University and Lurie Children’s Hospital. Customized didactic, experiential, and professional development activities will complement mentored research experience to ensure that Dr. Perak attains her short-term training goals to gain expertise in, first, systems biology molecular methods and translation of mechanistic insights for clinical relevance, and second, clinical trials conduct. These plans and resources will ensure that in 5 years, Dr. Perak is a molecular epidemiologist and pediatric cardiologist who can lead multidisciplinary teams in translational research, taking new ideas through epidemiologic evalua- tion, mechanistic study, and clinical application, with a sustained impact on the field of pediatric CVH promotion.

项目概要/摘要 美国 25-54 岁成年人死于心血管疾病 (CVD) 的大多数与 饮食不理想。虽然饮食是成人 CVD 预防工作的一个重要目标，但对 儿童饮食可能更有效。动物数据表明，生命早期饮食具有独特的调节潜力 生物系统并持久地对儿童的生物学进行编程，以实现长期健康或疾病。然而，尽管 NHLBI 战略愿景目标 1 优先考虑饮食如何调节生物系统，例如微生态系统。 为了维持健康的生物群落和代谢组，仅存在有限的动物和观察性成人数据。目标 该应用的目的是定义饮食模式干预对肠道微生物组的分子影响，以及 幼儿的循环代谢组。这一目标将通过对资助的一项辅助研究来实现 测试为期 12 个月的预防高血压饮食方法 (DASH) 饮食干预效果的临床试验 3 至 5 岁儿童的肥胖和其他 CVH 指标（例如血压、血脂）（n=140）。使用 其他参与者样本、深度表型分析和高级生物信息学，拟议的工作将解决 三个具体目标。首先，它将测试 DASH 饮食干预对肠道微生物组的影响，包括 丰富的微生物类群、群落以及代谢相关基因和转录本。其次，它将定义 饮食和肠道微生物组与循环代谢组的关联。使用目标和非目标 将评估代谢组学方法、血液代谢物、代谢物网络和代谢途径。 最后，它将以探索性的方式探讨饮食干预与随后的肥胖之间的联系途径 和 CVH 指标，通过肠道微生物组和血清代谢组。预期结果是初步的 DASH 饮食如何改变幼儿肠道微生物组和循环代谢组的模型，以及如何 这些改变与短期 CVH 结果相关。这些试点数据可以在更大的样本中得到验证，并且 从而有助于最终开发新颖的、有针对性的生命早期饮食策略，以保持理想的 CVH。 拟议的研究还将用作医学博士 Amanda Marma Perak 的培训平台，她的目标是 拥有一个独立的转化研究项目，专注于了解 CVH 的早期决定因素 制定保留终生 CVH 的策略。一个由杰出科学家组成的团队将提供指导 西北大学和卢里儿童医院拥有丰富的研究发展环境。定制 教学、体验和专业发展活动将补充指导研究经验， 确保 Perak 博士实现她的短期培训目标，首先获得系统生物学分子方面的专业知识 临床相关性的方法和机制见解的转化，第二，临床试验的进行。这些 计划和资源将确保 Perak 博士在 5 年内成为一名分子流行病学家和儿科心脏病专家 谁可以领导多学科团队进行转化研究，通过流行病学评估吸收新想法 化、机制研究和临床应用，对儿科 CVH 推广领域产生持续影响。

项目成果

Associations of gestational cardiovascular health with pregnancy outcomes: the Hyperglycemia and Adverse Pregnancy Outcome study.

妊娠心血管健康与妊娠结局的关联：高血糖和不良妊娠结局研究。

• DOI: 10.1016/j.ajog.2020.07.053
• 发表时间: 2021-03
• 期刊: American journal of obstetrics and gynecology
• 影响因子: 9.8
• 作者: Perak AM;Lancki N;Kuang A;Labarthe DR;Allen NB;Shah SH;Lowe LP;Grobman WA;Scholtens DM;Lloyd-Jones DM;Lowe WL Jr;Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group
• 通讯作者: Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group

Associations of glycemia and lipid levels in pregnancy with dyslipidemia 10-14 years later: The HAPO follow-up study.

• DOI: 10.1016/j.diabres.2022.109790
• 发表时间: 2022-03
• 期刊: DIABETES RESEARCH AND CLINICAL PRACTICE
• 影响因子: 5.1
• 作者: Lowe, Lynn P.;Perak, Amanda M.;Kuang, Alan;Lloyd-Jones, Donald M.;Sacks, David A.;Deorochanawong, Chaicharn;Maresh, Michael;Ma, Ronald C.;Lowe, William L., Jr.;Metzger, Boyd E.;Scholtens, Denise M.
• 通讯作者: Scholtens, Denise M.

Editorial commentary: Lessons learned and unanswered questions about weight changes throughout the life course and cardiovascular disease.

编辑评论：关于整个生命过程中体重变化和心血管疾病的经验教训和未解答的问题。

• DOI: 10.1016/j.tcm.2019.02.009
• 发表时间: 2020
• 期刊: Trends in cardiovascular medicine
• 影响因子: 9.3
• 作者: Perak,AmandaM;Khan,SadiyaS
• 通讯作者: Khan,SadiyaS

Age-Related Development of Cardiac Remodeling and Dysfunction in Young Black and White Adults: The Coronary Artery Risk Development in Young Adults Study.

• DOI: 10.1016/j.echo.2020.11.002
• 发表时间: 2021-04
• 期刊: Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
• 作者: Perak AM;Khan SS;Colangelo LA;Gidding SS;Armstrong AC;Lewis CE;Reis JP;Schreiner PJ;Sidney S;Lima JAC;Lloyd-Jones DM
• 通讯作者: Lloyd-Jones DM

Associations of Late Adolescent or Young Adult Cardiovascular Health With Premature Cardiovascular Disease and Mortality.

• DOI: 10.1016/j.jacc.2020.10.002
• 发表时间: 2020-12-08
• 期刊: Journal of the American College of Cardiology
• 影响因子: 24
• 作者: Perak AM;Ning H;Khan SS;Bundy JD;Allen NB;Lewis CE;Jacobs DR Jr;Van Horn LV;Lloyd-Jones DM
• 通讯作者: Lloyd-Jones DM