Impact of Breast Milk on Infant Gut Microbiome

肠道微生物组在免疫系统的发育和免疫系统的改变中起着关键作用。 微生物组的多样性几乎肯定在过敏性和非传染性疾病的激增中起着重要作用。 发达国家的炎症性疾病。婴儿肠道微生物组在婴儿出生后的前2年内发育 生活，和WHEALS出生队列表明，母乳喂养是影响婴儿最重要的因素， 肠道微生物组组成。然而，母乳具有几种生物活性物质，可以调节微生物的生长， 母乳喂养是一种简单的哺乳方式，在母乳喂养的粗略定义中并没有体现出来。人乳寡糖 （HMO）是复杂的聚糖，不易被人类消化，并且是婴儿肠道的主要底物之一 微生物群直到断奶。根据刘易斯的血型、分泌状态和饮食，母乳具有 HMO成分的定性和定量存在显著差异。此外，母乳也 已被证明是细菌物种的来源，这些细菌物种在婴儿肠道中定植。最后，伊加和IgA诱导 细胞因子反映母体暴露，也控制肠道微生物组组成。这些发现支持 母乳在决定生命早期微生物组成方面的重要作用。然而，人乳 组成显着不同的母亲，这些因素对婴儿肠道的相对贡献 微生物是未知的。 本申请的总体目标是定义人乳生物活性物质如何支持以下方面的开发： 婴儿肠道微生物组和代谢组。我们的中心假设是，与现代生活方式有关的生活方式因素 生活方式增加了微生物群失调的风险，并促进过敏，部分原因是缺乏 母乳的积极调节。我们的初步数据从旧秩序门诺派（OOM）与丰富的 暴露于农场和未经巴氏消毒的牛奶表明，他们有哮喘和过敏的发病率低， 疾病和母乳具有更多样化的微生物组和高水平的伊加。我们将确定乳房 不同暴露量的不同母亲人群中的乳汁生物活性成分（目标1）， 表征婴儿肠道微生物组和代谢组的组成，并评估 母乳成分对婴儿肠道微生物组和代谢组的影响（目标2）。该项目成立于 在我们CTSI资助的OOM试点研究中，在1-2个月时收集母乳和粪便样本， 来自母乳喂养的OOM（n=58）和罗切斯特（n=34）母婴对。 我们希望确定影响婴儿肠道发育的关键母乳成分 微生物组和代谢组。最终目标是建立产妇干预措施，以改变母乳 本发明提供了一种组合物，以有利于保护免受过敏性和非传染性炎性疾病。

The gut microbiome plays a critical role in the development of the immune system and alterations in the microbiome diversity almost certainly play an important role in the surge of allergic and noncommunicable inflammatory diseases in developed nations. The infant gut microbiome develops over the first 2 years of life, and the WHEALS birth cohort showed that breastfeeding is the most significant factor impacting infant gut microbiome composition. However, breast milk has several bioactives that can modulate microbial composition and are not captured in a coarse definition of breastfeeding. Human milk oligosaccharides (HMOs) are complex glycans, non-digestible by humans, and one of the main substrates for the infant gut microbiota until weaning. Depending on the Lewis blood group, secretor status and diet, mothers' milk has significant variations in qualitative and quantitative HMO composition. Furthermore, breast milk has also been shown to act as a source of bacterial species that colonize the infant gut. Finally, IgA and IgA-inducing cytokines reflect maternal exposures and also control gut microbiome composition. These findings support a strong role for breast milk in determining early life microbial composition. However, human milk composition varies significantly between mothers, and the relative contribution of these factors on infant gut microbiome is, however, unknown. The overall objective of this application is to define how human milk bioactives support the development of infant gut microbiome and metabolome. Our central hypothesis is that life-style factors related to modern lifestyle increase the risk for dysbiotic microbiome and promote allergies, in part mediated via lack of positive modulation by breast milk. Our preliminary data from the Old Order Mennonites (OOM) with rich exposure to farms and unpasteurized milk suggest that they have a low prevalence of asthma and allergic diseases and breast milk with a more diverse microbiome and high levels of IgA. We will determine breast milk bioactive components in a diverse population of mothers with varying exposure (Aim 1) and characterize the composition of infant gut microbiome and metabolome and assess the contribution of breast milk composition to infant gut microbiome and metabolome (Aim 2). The proposed project is founded on our CTSI-funded OOM pilot study in which breast milk and stool samples were collected at 1-2 months from breastfeeding OOM (n=58) and Rochester (n=34) mother-infant pairs. We expect to identify the key human milk components that impact the development of infant gut microbiome and metabolome. The ultimate goal is to establish maternal interventions to modify breast milk composition to favor protection against allergic and non-communicable inflammatory diseases.