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的孩子患过敏性哮喘的风险很高。虽然

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.