Impact of Breast Milk on Infant Gut Microbiome

肠道微生物群在免疫系统的发展和免疫系统的改变中起着至关重要的作用。 微生物群的多样性几乎肯定在过敏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。婴儿肠道微生物群在婴儿出生后的头两年内发育。 生命，而WHEALS出生队列表明，母乳喂养是影响婴儿的最重要因素 肠道微生物群组成。然而，母乳中有几种生物活性物质可以调节微生物 不包括在母乳喂养的粗略定义中。人乳低聚糖 (HMOS)是一种复杂的多糖，不能被人类消化，也是婴儿肠道的主要底物之一 直到断奶前的微生物群。根据刘易斯血型、分泌物状态和饮食，母乳中有 HMO的定性和定量组成存在显著差异。此外，母乳也有 已被证明是定植于婴儿肠道的细菌物种的来源。最后，免疫球蛋白A和诱导免疫球蛋白 细胞因子反映了母亲的暴露，也控制了肠道微生物群的组成。这些发现支持 母乳在确定早期生命微生物组成方面的重要作用。然而，人类乳汁 母亲之间的组成差异很大，这些因素对婴儿肠道的相对贡献 然而，微生物组是未知的。 本申请的总体目标是定义母乳生物活性物质如何支持 婴儿肠道微生物组和代谢组。我们的中心假设是，生活方式因素与现代 生活方式增加了微生物群失调的风险，并促进了过敏，部分是通过缺乏 母乳的正向调节作用。我们来自富集区旧序门诺石(OOM)的初步数据 接触农场和未经巴氏灭菌的牛奶表明，他们哮喘和过敏的患病率较低。 疾病和母乳具有更多样的微生物群和较高的IgA水平。我们要做乳房检查 不同母亲人群中的乳汁生物活性成分(目标1)和 描述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)。提议的项目成立了 在我们由CTSI资助的OOM试点研究中，母乳和粪便样本在1-2个月时采集 来自母乳喂养的OOM(n=58)和Rochester(n=34)母婴配对。 我们希望找出影响婴儿肠道发育的关键母乳成分。 微生物组和代谢组。最终的目标是建立母体干预措施来修改母乳 有利于预防过敏性和非传染性炎症的组合物。

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.