Role of breast milk in development of neonatal oral tolerance to foods

描述（由申请人提供）：目前，关于过敏或非过敏家庭的过敏预防，孕妇和哺乳期母亲缺乏明确的饮食建议，尽管非常需要有坚定的循证指南来为家庭提供建议。在怀孕和哺乳期间严格避免食物过敏原（如花生）对婴儿食物过敏风险的影响的人体研究很难进行，而且可能是不道德的。动物研究表明，免疫耐受是通过围产期喂养抗原诱导的。这些研究评估了幼稚母亲患ova诱发哮喘的风险，评估了花生过敏母亲患花生过敏的风险。这项提议的新颖之处在于评估那些对所讨论的食物有耐受性的母亲，这与大多数人类有关。因此，在目前的建议中，我们旨在通过花生过敏动物模型来解决哺乳期间喂养花生对后代过敏致敏易感性的影响。我们还旨在确定通过母乳提供的口服耐受性发展的潜在机制。这些动物研究将为母婴喂养指南建立生物学基础，以解决日益频繁的食物过敏问题。一旦这种预防或增加食物过敏风险的基本机制被发现，未来的研究可以在选择或不选择坚持避免饮食的母亲的人类队列中进行。

DESCRIPTION (provided by applicant): Currently, clear dietary recommendations for pregnant and breastfeeding mothers are lacking regarding allergy prevention in allergic or non-allergic families, although there is a great need to have firm evidence-based guidelines to advise families. Human studies to investigate the effect of strict food allergen avoidance, such as peanut, during pregnancy and lactation on the infant's risk towards development of food allergy are difficult to perform and potentially unethical. Animal studies have suggested that tolerance is induced by perinatal feeding of antigen. These studies have assessed naive mothers to assess risk of OVA-triggered asthma and peanut-allergic mothers to assess risk of peanut allergy. The novelty of this proposal is to assess mothers who are tolerant to the food in question, which is relevant to most of the humans. In the current proposal, we therefore aim to address the effect of feeding peanut during lactation on the offspring's predisposition toward allergic sensitization using an animal model of peanut allergy. We also aim to determine the potential mechanism of oral tolerance development provided via maternal milk. These animal studies will establish biological basis for maternal and infant feeding guidelines in order to address the increasing frequency of food allergies. Once basic mechanisms of this protection against or increased risk towards food allergy have been detected, the future studies could be performed in a human cohort of mothers who choose or do not choose to adhere to avoidance diets. My immediate goal is to obtain intensive training in immunobiology and experimental models of food allergy to add to my skills in mucosal immunology and maternal-infant interface of immunity. As a long-term goal, I strive to pursue a career in translational research to utilize both my skills in basic research as well as patient care and with that would like to develop into an independent research investigator. The proposed career development activities are a combination of coursework and informal training that will strengthen my knowledge and research skills in immunobiology applied to oral tolerance development. The Pediatric Allergy and Immunology Division and The Immunology Institute Mount Sinai School of Medicine provide an excellent forum for these activities, which include informal interactions with the faculty as well as formal courses in immunobiology and biostatistics, journal clubs, seminars and work-in- progress presentations, as well as training in responsible conduct of research. NARRATIVE: This research aims to solve a health concern of great public interest: should breastfeeding mothers avoid or eat potential food allergens in order to avoid development of food allergy in their children.