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

描述（由申请人提供）：目前，在过敏或非过敏家庭中，缺乏针对孕妇和哺乳期母亲的明确的过敏预防饮食建议，尽管非常需要有坚定的循证指南来建议家庭。人类研究调查在怀孕和哺乳期间严格避免食物过敏原（如花生）对婴儿发生食物过敏风险的影响是难以进行的，并且可能是不道德的。动物研究表明，耐受性是由围产期喂养抗原诱导的。这些研究评估了未怀孕的母亲，以评估OVA引发哮喘的风险，并评估了花生过敏的母亲，以评估花生过敏的风险。这项建议的新奇在于评估对所讨论的食物具有耐受性的母亲，这与大多数人类有关。因此，在目前的建议中，我们的目标是解决在哺乳期喂养花生对后代的易感性，对过敏性致敏使用花生过敏的动物模型的影响。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。一旦发现这种防止食物过敏或增加食物过敏风险的基本机制，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。 我的近期目标是获得免疫生物学和食物过敏实验模型的强化培训，以增加我在粘膜免疫学和母婴免疫界面方面的技能。作为一个长期目标，我努力追求在转化研究的职业生涯，利用我在基础研究以及病人护理的技能，并希望发展成为一个独立的研究调查员。拟议的职业发展活动是课程和非正式培训的结合，将加强我在应用于口服耐受性发展的免疫生物学方面的知识和研究技能。儿科过敏和免疫学部门和免疫学研究所西奈山医学院为这些活动提供了一个很好的论坛，其中包括与教师的非正式互动以及免疫生物学和生物统计学，期刊俱乐部，研讨会和工作的正式课程进展中的演示文稿，以及负责任的研究行为的培训。 说明：这项研究旨在解决一个公众关注的健康问题：母乳喂养的母亲是否应该避免或食用潜在的食物过敏原，以避免其子女发生食物过敏。

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.