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.

肠道微生物组在免疫系统的发展中起着至关重要的作用 微生物组的多样性几乎可以肯定在过敏和非传播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最初的两年中发展 生命和惠利人的出生队列表明，母乳喂养是影响婴儿的最重要因素 肠道微生物组组成。但是，母乳有几种可以调节微生物的生物活性剂 成分，并未在母乳喂养的粗糙定义中捕获。人乳寡糖 （HMOS）是复杂的聚糖，人类不可消化，而婴儿肠道的主要底物之一 微生物群直到断奶。根据刘易斯血统，秘书状态和饮食，母亲的牛奶有 定性和定量HMO组成的显着变化。此外，母乳也有 被证明充当定植婴儿肠道的细菌物种的来源。最后，IgA和IgA诱导 细胞因子反映了母体暴露，还可以控制肠道微生物组组成。这些发现支持 母乳在确定早期生命微生物组成中的重要作用。但是，人牛奶 母亲之间的组成和这些因素对婴儿肠道的相对贡献差异很大 但是，微生物组是未知的。 该应用的总体目的是定义人类牛奶生物活性剂如何支持的发展 婴儿肠道微生物组和代谢组。我们的中心假设是与现代有关的生活方式 生活方式增加了生病微生物组并促进过敏的风险，部分原因是 母乳调节阳性。我们的初步数据来自旧订单mennonites（OOM） 暴露于农场和未经巴氏菌的牛奶表明它们的哮喘患病率很低 具有更多样化的微生物组和高水平IgA的疾病和母乳。我们将确定乳房 牛奶生物活性成分在各种各样的母亲种群中，暴露量不同（AIM 1）和 表征婴儿肠道微生物组和代谢组的组成，并评估 婴儿肠道微生物组和代谢组的母乳组成（AIM 2）。拟议的项目建立 在我们由CTSI资助的OOM试点研究中，在1-2个月中收集母乳和粪便样品 从母乳喂养的OOM（n = 58）和罗切斯特（n = 34）的母亲对。 我们希望确定影响婴儿肠发展的关键人牛奶成分 微生物组和代谢组。最终目标是建立孕产妇干预措施以修饰母乳 组成，有利于保护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.

• DOI: 10.1371/journal.pone.0267967
• 发表时间: 2022
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Holm, Matilda;Saraswat, Mayank;Joenvaara, Sakari;Seppo, Antti;Looney, R. John M.;Tohmola, Tiialotta;Renkonen, Jutta;Renkonen, Risto;Jarvinen, Kirsi
• 通讯作者: Jarvinen, Kirsi