Multi-Omics Analysis of the Association of Polyunsaturated Fatty Acids with Asthma and Allergy in Childhood

多不饱和脂肪酸与儿童哮喘和过敏关联的多组学分析

• 批准号: 10461866
• 负责人: Kathleen A Lee-Sarwar
• 金额: $ 17.06万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-05 至 2023-08-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461866
• 关键词: 3 year old; 7 year old; Address; Allergic; Allergic Disease; Allergic inflammation; Anti-Inflammatory Agents; Asthma; Bacteria; Behavioral; Bioinformatics; Biological Availability; Chemicals; Child; Childhood; Childhood Asthma; Chronic Disease; Classification; Clinical; Clinical Research; Data; Development Plans; Diet; Dietary Factors; Dietary Fats; Dietary Fatty Acid; Dietary Intervention; Dietary intake; Disease; Environment; Epidemiology; Fellowship; Financial cost; Genes; Genetic; Genotype; Goals; Hypersensitivity; Immunologics; Immunology; Individual; Inflammation; Instruction; Intake; Intervention; Intestines; Investigation; Lead; Life; Mediating; Mentors; Metabolism; Metagenomics; Methods; Multiomic Data; Omega-3 Fatty Acids; Omega-6 Fatty Acids; Participant; Pathway interactions; Pattern; Persons; Physicians; Plasma; Polyunsaturated Fatty Acids; Preparation; Prevalence; Probiotics; Process; Prospective Studies; Recurrence; Reporting; Research; Research Methodology; Research Personnel; Research Proposals; Risk; Risk Factors; Training; Training Programs; Translational Research; Variant; Vitamin D; Vitamin D supplementation; Vocational Guidance; Volatile Fatty Acids; Wheezing; Work; antenatal; base; career; career development; clinically relevant; cost effective; defined contribution; dietary; dysbiosis; environmental allergy; experience; fatty acid metabolism; fatty acid supplementation; follow-up; genetic variant; gut bacteria; gut microbiota; immune function; learning strategy; lipid mediator; machine learning algorithm; machine learning method; medical schools; metabolome; microbial; microbiome; microbiota; multiple omics; nutrition related genetics; personalized approach; precision medicine; prevent; professor; response; skills; statistical learning; study population; western diet

PROJECT SUMMARY This K08 proposal describes a comprehensive training program tailored to the career development of the candidate. The candidate is a physician who recently completed a clinical fellowship in Allergy and Immunology and whose research contributions to date have addressed early-life risk factors for childhood asthma and allergy with a focus on the diet and intestinal microenvironment. Asthma and environmental allergies have increased in prevalence and asthma is now the most common chronic disease in children. The increased occurrence of asthma and allergy has been attributed to changes including dietary shifts and dysbiosis, though contributory factors are incompletely defined and interventions to prevent asthma and allergy remain elusive. Polyunsaturated fatty acids (PUFA), including omega-3 and omega-6 fatty acids (FA) have well-defined immunologic effects, and the ratio of omega-6:omega-3 FA intake has increased concurrently with the increase in allergic disease. However, reported associations of PUFA with asthma and allergy in childhood are inconsistent. The overarching hypothesis of this proposal is that effects of PUFA are impacted by host genotype and the intestinal microbiota. Our scientific goal is to examine these omics to identify determinants of when a safe and inexpensive intervention, intake of PUFA, is effective in reducing asthma and allergy in childhood. We will utilize data from 6- and 7-year-old participants in three study populations: Vitamin D Antenatal Asthma Reduction Trial (VDAART), Project Viva and Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC). We have three specific aims: (1) Identify gene by omega-3 FA interactions in asthma and allergy in childhood; (2): Define the contributions of intestinal bacteria and metabolites to associations of omega-3 FA dietary intake with asthma and allergy in childhood; and (3) Characterize clinically relevant childhood plasma PUFA profiles using unsupervised classification methods and integrative machine learning algorithms. Our findings could lead to cost-effective and personalized approaches to asthma and allergy reduction by elucidating which individuals benefit from dietary PUFA supplementation and whether microbiota-modifying therapies could boost protective responses to PUFA. The candidate proposes to execute this research plan alongside a training and development plan including hands-on bioinformatics instruction and preparation for independent mechanistic and clinical R01-level follow-up projects. The proposed work will be mentored by Dr. Scott Weiss, a Professor at Harvard Medical School and a leader in environmental, nutritional and genetic asthma risk factors. The candidate will obtain additional scientific input and career guidance from a team including a co-mentor and three scientific advisors with expertise in asthma epidemiology, lipid mediators of allergic inflammation, multi-omics analysis and translational research methods. This proposal represents a natural continuation of the candidate’s prior experience and will provided the support needed for her to become an independent investigator with a focus on precision medicine approaches to asthma and allergy.

项目摘要 本K 08建议书描述了一个针对以下人员职业发展的全面培训计划： 候选人候选人是一名医生，最近完成了过敏症的临床研究， 免疫学，其研究贡献迄今已解决了儿童早期生活的危险因素 哮喘和过敏，重点是饮食和肠道微环境。哮喘与环境 过敏症的流行率有所增加，哮喘现在是儿童中最常见的慢性疾病。的 哮喘和过敏的发生率增加归因于包括饮食变化在内的变化， 生态失调，虽然贡献因素不完全定义和干预措施，以防止哮喘和过敏 仍然难以捉摸。多不饱和脂肪酸（PUFA），包括ω-3和ω-6脂肪酸（FA），具有 明确的免疫效应，omega-6：omega-3 FA摄入量的比例同时增加， 过敏性疾病的增加。然而，据报道，儿童期多不饱和脂肪酸与哮喘和过敏的关系 不一致。该提案的首要假设是PUFA的影响受宿主影响 基因型和肠道菌群。我们的科学目标是检查这些组学，以确定 当一种安全而廉价的干预措施，即摄入PUFA，在减少哮喘和过敏方面有效时， 童年.我们将利用三个研究人群中6岁和7岁参与者的数据： 儿童哮喘减轻试验（VDAART）、Viva项目和哥本哈根前瞻性研究 《2010年儿童》（COPSAC）。我们有三个具体的目标：（1）通过omega-3 FA相互作用识别基因， 儿童哮喘和过敏;（2）：定义肠道细菌和代谢产物对 儿童期omega-3 FA饮食摄入与哮喘和过敏的关系;以及（3）临床表征 使用无监督分类方法和集成机器的相关儿童血浆PUFA谱 学习算法我们的研究结果可能会导致成本效益和个性化的方法来治疗哮喘， 通过阐明哪些个体受益于膳食PUFA补充剂以及是否 微生物修饰疗法可以增强对PUFA的保护反应。候选人提议执行 该研究计划以及培训和发展计划，包括动手生物信息学教学， 为独立的机制和临床R 01级后续项目做准备。拟议的工作将是 由哈佛医学院教授、环境、营养和健康领域的领导者斯科特韦斯博士指导。 和遗传性哮喘风险因素。候选人将获得额外的科学投入和职业指导， 团队包括一名共同导师和三名科学顾问，他们在哮喘流行病学、脂质介质 过敏性炎症、多组学分析和转化研究方法。该提案代表了 候选人先前经验的自然延续，并将为她提供所需的支持， 一个独立的研究者，专注于哮喘和过敏的精确医学方法。

项目成果

Omega-3 Fatty Acids Interact with DPP10 Region Genotype in Association with Childhood Atopy.

• DOI: 10.3390/nu15102416
• 发表时间: 2023-05-22
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Lee-Sarwar KA;Fischer-Rasmussen K;Bønnelykke K;Bisgaard H;Chawes B;Kelly RS;Lasky-Su J;Zeiger RS;O'Connor GT;Bacharier LB;Carey VJ;Laranjo N;Litonjua AA;Weiss ST
• 通讯作者: Weiss ST