Project 2 Maternal Factors and their Effect on a Child's Gut Microbiota and Ige Production

项目 2 母体因素及其对儿童肠道菌群和 Ige 产生的影响

• 批准号: 10480065
• 负责人: EDWARD M ZORATTI
• 金额: $ 2.88万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-06 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10480065
• 关键词: 2 year old; Affect; Age; Age-Months; Allergens; Allergic; Antibiotics; Antibodies; Asthma; Birth; Blood; Blood specimen; Breast Feeding; Breastfed infant; Characteristics; Child; Childhood; Cohort Studies; Communities; Data; Development; Diet; Dietary Factors; Disease; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiology; Extrinsic asthma; Feces; Feeding Patterns; Gastrointestinal tract structure; Genetic; Human; Human Milk; Hypersensitivity; IgE; Immune; Immune System Diseases; Immune response; Immune system; Immunoassay; Infant; Infant Development; Intervention; Knowledge; Life; Link; Lipids; Meconium; Metabolic; Microbe; Mothers; Neonatal; Newborn Infant; Odds Ratio; Pattern; Phenotype; Predisposition; Pregnancy; Pregnant Women; Prevention strategy; Primary Prevention; Production; Research; Risk; Sampling; Scientific Advances and Accomplishments; Shapes; Signal Transduction; Specimen; Stimulus; Surveys; Susceptibility Gene; Swab; Techniques; Testing; Time; Vagina; Vertical Disease Transmission; Woman; child bearing; cohort; early pregnancy; feeding; fetal; gut microbes; gut microbiota; high risk; individualized prevention; liquid chromatography mass spectrometry; maternal microbiota; microbial; microbial community; microbiota; neonatal period; neonate; perinatal environment; pet animal; prenatal; rational design; stool sample; tobacco smoke exposure; transmission process; vaginal microbiota

Women with allergy-related asthma bear children at high risk for developing allergic asthma. Although genetic factors partially explain this elevated risk, maternal transfer of some of the microbes that live in her body and transfer of selected microbe-produced metabolites to her child during pregnancy and the first month of life may also contribute to this high asthma risk. We hypothesize that the transfer of these microbes, that begin growing in a newborn's gastrointestinal tract, shape the infant's developing immune system in ways that affect his or her susceptibility to immune disorders like allergic asthma. We have identified a spectrum of factors during pregnancy and early life (such as diet, pet-keeping, breast feeding patterns) that are associated with microbes that inhabit the gastrointestinal tract of 1 month old infants. Manipulation of these factors that affect the types of microbes present in pregnant women and their newborns may be effective strategies to mitigate the child's risk of developing allergic asthma. This Project is focused on the following objectives: 1. Identify maternal and environmental factors during pregnancy and early life that are associated with the microbes present in a mother's gut and vaginal tract and also factors that influence the presence of certain lipid microbial metabolites in breastmilk that may alter an infant's production of IgE antibodies. 2. Determine how a mother's gut and vaginal microbes during pregnancy relate to the microbes and microbial lipid metabolites present in her baby's gastrointestinal tract during the first month of life. 3. Identify those patterns of gut microbes and their associated lipid metabolites during the first month of a baby's life that are associated with the infant's production of IgE antibodies and a specific pattern of IgE sensitization that has been linked to a high risk for developing allergic asthma in later childhood. We will identify 180 women during early pregnancy and confirm that they have allergic asthma to create a high-risk for allergic asthma mother/child cohort. Data to be collected will include detailed surveys, blood, vaginal swabs and stool specimens from the mother during pregnancy. Beginning at birth, we will continue surveys and begin collecting breastmilk specimens as well as blood and stool specimens from the infant. The bio-specimens will be probed using next-generation16SrRNA and ITS2 sequencing techniques to assess the bacterial and fungal communities in the stool and vaginal swab samples, established immunoassay techniques will be used to determine IgE level and allergen sensitization. Lipid metabolites in stool and breastmilk will be identified by liquid chromatography mass spectrometry. This research will advance scientific knowledge related to how the prenatal environment and maternal factors, including the maternal microbiota, shape a neonate's initial gut microbiota and allergic immune responses, and will be useful to inform primary prevention strategies for allergic asthma.

患有过敏相关哮喘的女性生育的孩子患过敏性哮喘的风险很高。虽然 遗传因素部分解释了这种升高的风险，体内某些微生物的母体转移 怀孕期间和第一个月的身体以及将选定的微生物产生的代谢物转移给孩子 生活的不规律也可能导致这种高哮喘风险。我们假设这些微生物的转移 开始在新生儿的胃肠道中生长，以以下方式塑造婴儿正在发育的免疫系统： 影响他或她对过敏性哮喘等免疫疾病的易感性。我们已经确定了一系列 怀孕期间和生命早期的相关因素（例如饮食、养宠物、母乳喂养模式） 含有栖息在 1 个月大婴儿胃肠道中的微生物。对这些因素的操纵 影响孕妇及其新生儿体内存在的微生物类型可能是有效的策略 降低孩子患过敏性哮喘的风险。该项目的重点是以下目标： 1. 确定怀孕期间和生命早期与妊娠相关的母亲和环境因素 母亲肠道和阴道中存在的微生物以及影响某些脂质存在的因素 母乳中的微生物代谢物可能会改变婴儿 IgE 抗体的产生。 2. 确定怀孕期间母亲的肠道和阴道微生物与微生物之间的关系，以及 婴儿出生第一个月胃肠道中存在微生物脂质代谢物。 3. 确定婴儿出生后第一个月内肠道微生物及其相关脂质代谢物的模式 婴儿的一生与婴儿 IgE 抗体的产生以及 IgE 的特定模式相关 过敏与儿童后期患过敏性哮喘的高风险有关。 我们将对180名怀孕早期的女性进行识别，确认她们患有过敏性哮喘，以创建一个 过敏性哮喘母亲/儿童群体的高风险人群。收集的数据将包括详细调查、血液、 怀孕期间母亲的阴道拭子和粪便标本。从出生开始，我们将继续 调查并开始收集婴儿的母乳样本以及血液和粪便样本。这 将使用下一代 16SrRNA 和 ITS2 测序技术对生物样本进行探测，以评估 粪便和阴道拭子样本中的细菌和真菌群落，已建立的免疫测定技术 将用于确定 IgE 水平和过敏原致敏性。 粪便和母乳中的脂质代谢物将通过液相色谱质谱法进行鉴定。 这项研究将增进有关产前环境和母亲如何影响的科学知识。 包括母体微生物群在内的因素塑造了新生儿的初始肠道微生物群和过敏性免疫 反应，并将有助于为过敏性哮喘的一级预防策略提供信息。