Human Milk Cytokines and Oligosaccharides in Development of Allergic Diseases

食物过敏和特应性皮炎通常会引发婴儿的“过敏进行曲”。 根据疾控中心的说法，食物引起的过敏反应是过敏和过敏的首要原因。 疾病是影响美国儿童的最常见的医疗条件之一。 各州。尽管呼吸道过敏没有明显的趋势，但它们仍然是最常见的 儿童中常见的过敏类型(2009-2011年为17.0%)。过敏性疾病和哮喘 造成严重的经济负担和生活质量问题。遗传是一个强有力的决定因素，但 环境因素，包括西方的生活方式、微生物暴露和饮食可能起到了一定的作用 在特应性疾病上升中的作用。在这些因素中，考虑到母乳可能起到关键作用 母亲的特应性状态比父亲的特应性状态对特应性疾病的结局有更大的影响 后代。系统评价和荟萃分析得出了一个全面的保护作用 母乳喂养预防儿童早期特应性皮炎、喘息和牛奶过敏，但 确切的机制尚不清楚。 人乳低聚糖(HMO)是婴儿肠道的主要底物 微生物区系，从而在推动其多样性方面发挥着突出作用。人类观察性研究 已经报告了肠道微生物区系组成的失衡，这种失衡发生在疾病发生之前 特应性和特应性湿疹。此外，母乳是免疫刺激和 调节性细胞因子，其中一些与保护或风险因素有关 婴儿有过敏反应。我们的长期目标是了解母乳在发育中的作用 抗/亲过敏免疫反应。这个应用程序的总体目标是扩展我们的 了解全乳细胞因子和低聚糖组成与 过敏症状的发展。我们的中心假设是母乳具有生物活性 物质是正常肠道成熟过程的一部分，促进新生儿的发育 肠道微生物群和抗过敏免疫反应，这在过敏时会改变。我们将评估 人乳细胞因子包括促炎细胞因子、Th2-细胞因子和Th2-细胞因子 利用两个历史队列对剩余母乳进行HPLCTh17型细胞因子和HMOS的研究 追踪儿童患过敏性疾病的样本。生物活性水平 过敏性和非过敏性孩子的母亲的牛奶之间的物质将进行比较 运用系统生物学方法和Logistic回归分析。该计划的基本原理 提出的研究是为了解母乳成分奠定基础 对其抗过敏特性进行干预研究。

Food allergy and atopic dermatitis typically start the “allergic march” in an infant. According to CDC, food-induced anaphylaxis is the leading cause for anaphylaxis and allergic conditions are among the most common medical conditions affecting children in the United States. Although there is no significant trend in respiratory allergies, they remain the most common type of allergy among children (17.0% in 2009–2011). Allergic diseases and asthma pose significant economic burden and quality of life issues. Heredity is a strong determinant but environmental factors, including a western lifestyle, microbial exposures and diet likely play a role in the rise atopic diseases. Among those, human milk may play a critical role considering that maternal, rather than paternal atopic status has a greater effect on the atopic outcome of progeny. Systematic reviews and meta-analyses have concluded an overall protective effect of breastfeeding against atopic dermatitis, wheezing and cow's milk allergy in early childhood, but the exact mechanism is unknown. Human milk oligosaccharides (HMO) provide the main substrate for infant's gut microbiota, thereby playing a prominent role in driving its diversity. Human observational studies have reported imbalances in gut microbiota composition that precedes the development of atopy and atopic eczema. Additionally, human milk is a rich source of immunostimulatory and regulatory cytokines, some of which have been associated with protection or risk factors for allergies in the infant. Our long-term goal is to understand the role of breast milk in development of anti/pro-allergic immune responses. The overall objective of this application is to expand our understanding of entire milk cytokine and oligosaccharide composition in relation to development of allergic conditions. Our central hypothesis is that breast milk bioactive substances are part of the normal gut maturation process and promote development of neonatal gut microbiome and anti-allergic immune responses, which is altered in allergy. We will assess human milk cytokine composition by multiplex platform including proinflammatory, Th2- and Th17-type cytokines and HMOs by HPLC utilizing two historical cohorts with leftover breast milk samples that followed children for development of allergic diseases. Levels of bioactive substances will be compared between milk from mothers with allergic or non-allergic children utilizing systems biology approach and logistic regression analyses. The rationale for the proposed research is to understand human milk composition to establish the basis for interventional studies to modify its anti-allergic properties.