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.

项目摘要/摘要 在25-54岁的美国成年人中，大多数因心血管疾病（CVD）死亡是相关的 次优饮食。饮食是成人CVD预防工作的重要目标，但干预 儿童饮食可能更有效。动物数据表明，早期饮食具有调节的独特潜力 生物系统和耐用计划的儿童生物学，用于长期健康或疾病。但是，虽然是NHLBI的 战略视觉目标1优先考虑饮食如何调节生物系统（例如微型） 生物群和代谢组可维持健康，只有有限的动物和观察性成人数据才存在。目标 该应用是为了定义饮食模式干预对肠道微生物组和 幼儿循环代谢组。该目标将通过辅助研究附加到资助 临床试验测试了一种12个月的饮食方法，以阻止高血压（DASH）饮食中间 3至5岁儿童的肥胖和其他CVH指标（例如，血压，脂质）（n = 140）。使用 拟议的工作将解决其他参与样本，深层表型和高级生物信息学，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 微生物类群，社区以及与代谢相关的基因和成绩单的抽象。其次，它将定义 饮食与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，血液代谢产物，代谢产物网络和代谢途径。 最后，以探索性的方式，它将探测将饮食干预与随后的肥胖联系起来的途径 和CVH指标，通过肠道微生物组和血清代谢组。预期的结果是初步 破折号饮食如何改变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结果有关。这些试验数据可以在较大的样本中进行验证，并且 因此，有助于最终开发新颖的，有针对性的早期饮食策略，以保留理想的CVH。 拟议的研究还将被用作医学博士Amanda Marma Perak的培训平台，他的目标 要拥有一个独立的翻译研究计划，重点是理解早期生活的确定CVH 并制定保留终身CVH的策略。一个著名科学家团队将在 西北大学和卢里儿童医院的丰富研究发展环境。定制 教学，经验和专业发展活动将补充研究经验 确保Perak博士达到她的短期培训目标，以获得系统生物学分子的专业知识 临床相关性和第二个临床试验的机械见解的方法和翻译。这些 计划和资源将确保5年内，Perak博士是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，通过流行病学评估来采用新的想法 - tion，机械研究和临床应用，对小儿CVH促进领域产生持续影响。

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