VDAART FLORA ANCILLARY STUDY

VDAART 植物群辅助研究

• 批准号: 8238375
• 负责人: DIANE R GOLD
• 金额: $ 42.05万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8238375
• 关键词: 1 year old; 3 year old; Adult; Age; Age-Months; Allergens; Allergic; Allergic Disease; Allergic rhinitis; Anaerobic Bacteria; Ancillary Study; Anti-Inflammatory Agents; Anti-inflammatory; Asthma; Atopic Dermatitis; Bacteroides fragilis; Biology; Birth; CD4 Positive T Lymphocytes; Cells; Characteristics; Child; Childhood; Chronic; Clinical Trials; Development; Diagnosis; Diet; Dietary Intervention; Disease; Eczema; Enrollment; Exposure to; Extrinsic asthma; Frequencies; Funding; Gastrointestinal tract structure; Generations; Grant; Hay fever; Health; Helper-Inducer T-Lymphocyte; High Prevalence; Homing; Human; Hypersensitivity; Immune; Immune response; Immunology; Infant; Inflammatory; Interleukin-10; Intervention Trial; Intestines; Lactobacillus; Life; Link; Lymphoid Tissue; Microbiology; Mothers; Parents; Pathway interactions; Pilot Projects; Play; Population; Pregnancy; Prevalence; Public Health; Recurrence; Regulation; Regulatory T-Lymphocyte; Reporting; Research Design; Risk; Rodent; Role; Skin; Source; Sterility; Subgroup; Supplementation; T-Lymphocyte; Testing; Time; Translating; Umbilical Cord Blood; United States; United States National Institutes of Health; Urbanization; Vitamin D; Vitamin D Deficiency; Wheezing; abstracting; cytokine; disorder risk; follow-up; immune function; microbial; microorganism antigen; oral tolerance; postnatal; public health relevance; research study; response

DESCRIPTION (provided by applicant): Asthma is the most common cause of chronic childhood disease in the United States, and is a major health problem, particularly in urban pediatric populations. Most asthma is diagnosed before the age of six, and most children with asthma are atopic with sensitization to at least one allergen. Bacterial gut colonization and Vitamin D exposure are two factors that vary in children with urbanization, may influence immune function at the intestinal and systemic levels, and may increase the risk of allergy and asthma. In a small pilot study we found that the anti-inflammatory immunomodulatory cytokine IL-10 was increased in the cord blood of children whose mothers had a higher proportion of anaerobes in the gut. Infant gut diversity was protective against atopic dermatitis in the first 6 months of life. However, there has been no adequate long-term follow-up study of the gut flora in human early life and the development of atopic diseases. In the only U.S. pre-birth Vitamin D asthma intervention trial (NIH Grant number: U01 HL091528, co-PIs: Litonjua & Weiss), we have a unique opportunity to evaluate the influences of gut colonization (maternal and child) on the risk of early life wheeze, atopic dermatitis, and allergic sensitization. Moreover, this proposed ancillary study will optimize the chance to evaluate whether gut colonization and vitamin D influences on allergy and asthma development are independent or linked. We propose to test the following primary hypotheses in a subset of 200 mother:child pairs: (1) Higher levels of maternal vitamin D during pregnancy will increase numbers of total and specific anaerobes (B fragilis, and Lactobacillus) in the maternal and child intestinal flora; (2) Increased numbers of anaerobes in the maternal intestinal flora, and in the child intestinal flora at 4 months of age will reduce the risk of wheeze, recurrent wheeze (>2 reports of wheeze in the previous year), atopic dermatitis (eczema), and sensitization to >1 allergen at 1 year of age. We will consider exposures to total anaerobes, as well as the specific anaerobes B fragilis, and Lactobacillus; To further explore whether there are common pathways through which intestinal flora and vitamin D influence allergy and wheeze, we will test the following three secondary hypotheses: 3) Higher levels of maternal vitamin D during pregnancy will reduce the risk of recurrent wheeze, atopic dermatitis and sensitization in part through increasing numbers of anaerobes in the maternal intestinal flora, and in the child intestinal flora at 4 months of age. (4) Increased numbers of total and specific anaerobes in maternal and child intestinal flora will increase the frequency and anti-inflammatory function of Foxp3+ and IL-10+ Treg cells in cord blood.(5) Maternal supplementation with vitamin D during pregnancy will increase the diversity/complexity of maternal and child fecal flora. This proposal is time-sensitive. As ascertainment of the composition of maternal intestinal flora is central to our hypotheses, it is critically important that this ancillary study be initiated early in the final year (2011) of the enrollment and delivery period of the parent clinical trial VDAART. PUBLIC HEALTH RELVEANCE: Asthma is a major public health problem and the most common cause of chronic childhood disease in the United States. Over a 40 year period, allergic asthma, allergic rhinitis (hay fever) and atopic dermatitis (atopic eczema) prevalence increased, and the high prevalence of asthma persists, particularly in urban pediatric populations in the United States. If we identify components of maternal or childhood intestinal microbial flora that are protective against allergy, wheeze or asthma, and that vary with vitamin D levels or diet, this could be translated into pharmacologic or dietary interventions that would be of great benefit to public health. (End of Abstract)

描述（由申请人提供）：哮喘是美国儿童慢性疾病的最常见原因，是一个主要的健康问题，特别是在城市儿科人群中。大多数哮喘是在6岁之前被诊断出来的，大多数哮喘儿童是特应性的，对至少一种过敏原过敏。细菌肠道定植和维生素D暴露是城市化儿童中不同的两个因素，可能会影响肠道和全身水平的免疫功能，并可能增加过敏和哮喘的风险。在一项小型的试点研究中，我们发现，母亲肠道厌氧菌比例较高的儿童的脐带血中抗炎免疫调节细胞因子IL-10增加。婴儿肠道多样性在生命的前6个月内对特应性皮炎具有保护作用。然而，还没有足够的长期随访研究肠道植物群在人类早期生活和特应性疾病的发展。在美国唯一的产前维生素D哮喘干预试验（NIH批准号：U 01 HL 091528，共同PI：Litonjua &韦斯）中，我们有一个独特的机会来评估肠道定植（母亲和儿童）对生命早期喘息、特应性皮炎和过敏性致敏风险的影响。此外，这项拟议的辅助研究将优化评估肠道定植和维生素D对过敏和哮喘发展的影响是独立的还是相关的机会。我们建议在200对母亲：孩子的子集中测试以下主要假设：（1）怀孕期间母亲维生素D水平较高会增加总的和特定的维生素D水平。 母亲和儿童肠道植物群中厌氧菌（脆弱B和乳酸杆菌）的数量增加;（2）母亲肠道植物群和4个月大的儿童肠道植物群中厌氧菌数量增加将降低1岁时喘息、反复喘息（前一年喘息>2例报告）、特应性皮炎（湿疹）和对>1种过敏原致敏的风险。我们将考虑暴露于总厌氧菌以及特定的脆弱厌氧菌B和乳杆菌;为了进一步探索肠道植物群和维生素D是否存在影响过敏和喘息的共同途径，我们将检验以下三个次要假设：3）怀孕期间母体维生素D水平较高将降低反复喘息的风险，特应性皮炎和致敏部分通过母体肠道植物群和4个月大的儿童肠道植物群中厌氧菌数量的增加。(4)母体和儿童肠道植物群中厌氧菌总数和特异性厌氧菌数量的增加将增加脐带血中Foxp 3+和IL-10+ Treg细胞的频率和抗炎功能。(5)母亲在怀孕期间补充维生素D将增加母亲和儿童粪便植物群的多样性/复杂性。这项建议具有时效性。由于确定母体肠道植物群的组成是我们假设的核心，因此在母临床试验VDAART入组和分娩期的最后一年（2011年）早期启动这项辅助研究至关重要。公共卫生：哮喘是美国一个主要的公共卫生问题，也是儿童慢性疾病的最常见原因。在40年的时间里，过敏性哮喘、过敏性鼻炎（花粉热）和特应性皮炎（特应性湿疹）的患病率增加，并且哮喘的高患病率持续存在，特别是在美国的城市儿科人群中。如果我们确定母亲或儿童肠道微生物植物群的组成部分，这些组成部分可以防止过敏，喘息或哮喘，并且随着维生素D水平或饮食而变化，这可能会转化为对公共卫生非常有益的药理学或饮食干预。(End摘要）