Impact of Breast Milk on Infant Gut Microbiome

母乳对婴儿肠道微生物群的影响

• 批准号: 9756486
• 负责人: Kirsi Jarvinen-Seppo
• 金额: $ 25.03万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-08 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756486
• 关键词: 16S ribosomal RNA sequencing; Allergic; Allergic Disease; Asthma; Back; Biological; Birth; Breast Feeding; Categories; Childhood; Cities; Collaborations; Complex; Data; Developed Countries; Developing Countries; Development; Diet; Disease; Exposure to; Family; Farming environment; Funding; Goals; Health; High Pressure Liquid Chromatography; Human; Human Milk; Hypersensitivity; Immune system; Immunoglobulin A; Infant; Infant Development; Inflammatory; Institution; Interleukin-6; Intervention; Knowledge; Life; Life Style; Livestock; Low Prevalence; Mass Spectrum Analysis; Maternal Exposure; Measures; Mediating; Mennonite; Methods; Microbe; Milk; Modeling; Modernization; Mothers; Oligosaccharides; Outcome; Pilot Projects; Play; Polysaccharides; Population Heterogeneity; Prevention; Property; Research; Research Personnel; Risk; Role; Secretory Immunoglobulin A; Solid; Sorting - Cell Movement; Source; Statistical Methods; Time; Variant; Volatile Fatty Acids; Weaning; Work; base; blood group; breast milk microbiome; cohort; cytokine; dysbiosis; early childhood; early life exposure; feeding; gut microbiome; gut microbiota; immunoregulation; infant gut microbiome; lifestyle factors; metabolome; metabolomics; microbial; microbiome; microbiome alteration; microbiome composition; microbiome research; milk microbiome; precision medicine; response; stool sample; suburb; unpasteurized

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.

肠道微生物群在免疫系统的发育和免疫系统的改变中起着至关重要的作用 微生物组多样性几乎肯定在过敏性和非传染性疾病激增中发挥着重要作用 发达国家的炎症性疾病。婴儿肠道微生物群在出生后的头 2 年内发育 WHEALS 出生队列显示母乳喂养是影响婴儿的最重要因素 肠道微生物组的组成。然而，母乳具有多种可以调节微生物的生物活性物质 成分，并且没有包含在母乳喂养的粗略定义中。人乳低聚糖 (HMO) 是复杂的聚糖，人类不可消化，是婴儿肠道的主要底物之一 微生物群直至断奶。根据刘易斯血型、分泌状态和饮食，母乳具有 HMO 组成的定性和定量显着变化。此外，母乳还具有 已被证明是婴儿肠道中定植的细菌物种的来源。最后，IgA 和 IgA 诱导 细胞因子反映母体暴露情况，也控制肠道微生物组的组成。这些发现支持 母乳在决定生命早期的微生物组成方面发挥着重要作用。然而，人乳 母亲之间的成分存在显着差异，并且这些因素对婴儿肠道的相对贡献 然而，微生物组尚不清楚。 该应用的总体目标是确定母乳生物活性物质如何支持发育 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相关的因素 生活方式会增加微生物组失调的风险并促进过敏，部分原因是缺乏 母乳的积极调节。我们的初步数据来自旧秩序门诺派 (OOM)，具有丰富的 接触农场和未经高温消毒的牛奶表明他们的哮喘和过敏症患病率较低 疾病和母乳具有更多样化的微生物群和高水平的 IgA。我们将确定乳房 不同母亲群体中不同暴露程度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，并评估其贡献 母乳成分对婴儿肠道微生物组和代谢组的影响（目标 2）。拟建项目成立 CTSI 资助的 OOM 试点研究，在 1-2 个月时收集母乳和粪便样本 来自母乳喂养 OOM (n=58) 和罗切斯特 (n=34) 母婴对。 我们期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。最终目标是建立孕产妇干预措施来改变母乳 组合物有利于预防过敏性和非传染性炎症性疾病。

项目成果

Quantitative glycoproteomics of human milk and association with atopic disease.

母乳的定量糖蛋白组学及其与特应性疾病的关联。

• 发表时间: 2022
• 影响因子: 3.7
• 作者: Holm, Matilda;Saraswat, Mayank;Joenväärä, Sakari;Seppo, Antti;Looney, R John;Tohmola, Tiialotta;Renkonen, Jutta;Renkonen, Risto;Järvinen, Kirsi M
• 通讯作者: Järvinen, Kirsi M