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

患有过敏性哮喘的妇女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高风险，母体内生活的一些微生物的转移 在怀孕期间和第一个月期间选择的微生物产生的代谢物的身体和转移给她的孩子 寿命的延长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，塑造婴儿发育中的免疫系统， 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 与怀孕和早期生活相关的因素(如饮食、宠物饲养、母乳喂养方式) 1个月大的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。该项目侧重于以下目标： 1.找出孕期和早期与母体和环境因素有关的 存在于母亲肠道和阴道中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，可能会改变婴儿产生免疫球蛋白E抗体。 2.确定母亲怀孕期间的肠道和阴道微生物与微生物和 婴儿出生后第一个月胃肠道中的微生物脂类代谢物。 3.确定肠道微生物及其相关脂肪代谢物在第一个月的模式 婴儿的生活与婴儿产生IgE抗体和一种特定的IgE模式有关 致敏作用与儿童后期发展为过敏性哮喘的高风险有关。 我们将在怀孕早期识别180名女性，并确认她们患有过敏性哮喘，以创造一个 过敏性哮喘的高危母亲/儿童队列。收集的数据将包括详细的调查，血液， 母亲怀孕期间的阴道拭子和粪便样本。从出生开始，我们将继续 调查并开始收集母乳样本以及婴儿的血液和粪便样本。这个 生物标本将使用下一代16SrRNA和ITS2测序技术进行探测，以评估 粪便和阴道拭子样本中的细菌和真菌群落，建立了免疫分析技术 将用于测定IgE水平和过敏原致敏作用。 粪便和母乳中的脂类代谢物将用液相色谱质谱鉴定。 这项研究将推进与产前环境和产妇 因素，包括母亲的微生物区系，塑造新生儿最初的肠道微生物区系和过敏性免疫 这将有助于为过敏性哮喘的初级预防战略提供信息。

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.