VDAART FLORA ANCILLARY STUDY

VDAART 植物群辅助研究

• 批准号: 8448671
• 负责人: DIANE R GOLD
• 金额: $ 40.07万
• 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 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8448671
• 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）：哮喘是美国慢性儿童疾病的最常见原因，并且是一个主要的健康问题，尤其是在城市小儿种群中。大多数哮喘是在六岁之前诊断出来的，大多数哮喘儿童都在特定于至少一种过敏原。细菌肠道定植和维生素D暴露是城市化儿童不同的两个因素，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。在一项小型试点研究中，我们发现抗炎性细胞因子IL-10在肠道中母亲的厌氧菌比例较高的儿童的脐带血中增加了。婴儿肠道多样性在生命的头六个月中可防止特应性皮炎。但是，在人类早期生活和特应性疾病的发展中，没有足够的长期随访研究。在美国唯一的美国出生前维生素D哮喘干预试验（NIH赠款编号：U01 HL091528，Co-Pis：Litonjua＆Weiss）中，我们有一个独特的机会来评估肠道殖民（母性和儿童）对早期生命的风险的影响，对早期生命的风险，以及patopic Dermatitis to peropic Dermatitis and Axtrergic敏感性。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对过敏和哮喘发育的影响是独立的还是相关的。我们建议在200个母亲的子集中检验以下主要假设：儿童对：（1）妊娠期间较高的母体维生素D水平将增加总数和特定的数量 孕产妇和儿童肠菌群中的厌氧菌（B fragilis和乳杆菌）； （2）母体肠道菌群中的厌氧菌数量增加，在4个月时的儿童肠道菌群中，会降低喘息的风险，反复喘息的风险（>上一年喘息的报告），特应性皮炎（湿疹）（湿疹）（湿疹）和1岁时> 1个过敏原的敏感性。我们将考虑暴露于总厌氧菌以及特定的厌氧菌B fragilis和乳杆菌； 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）母亲和儿童肠道菌群中总数和特异性厌氧菌数量增加将增加脐带血中Foxp3+和IL-10+ Treg细胞的频率和抗炎功能。（5）怀孕期间用维生素D补充孕妇会增加母体和儿童的多样性/复杂性。该建议对时间敏感。由于确定母体肠道菌群的组成是我们假设的核心，因此在父母临床试验VDAART的入学和分娩期的最后一年（2011年）开始，这项辅助研究至关重要。公共卫生复制：哮喘是美国慢性儿童疾病的最常见原因。在40年内，过敏性哮喘，过敏性鼻炎（花粉症）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，特别是在美国城市小儿种群中。如果我们确定可抵抗过敏，喘息或哮喘的孕产妇或儿童肠道微生物菌群的组成部分，并且随维生素D水平或饮食的变化而变化，则可以将其转化为对公共卫生有很大益处的药理或饮食干预措施。 （抽象的结尾）

项目成果

Longitudinal Prediction of the Infant Gut Microbiome with Dynamic Bayesian Networks.

• DOI: 10.1038/srep20359
• 发表时间: 2016-02-08
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: McGeachie MJ;Sordillo JE;Gibson T;Weinstock GM;Liu YY;Gold DR;Weiss ST;Litonjua A
• 通讯作者: Litonjua A