DIVERSITY OF HUMAN MILK OLIGOSACCHARIDE METABOLIZING GENES IN TWO INFANT COHORTS

两个婴儿群体中母乳低聚糖代谢基因的多样性

• 批准号: 10358332
• 负责人: Vanja Klepac-Ceraj
• 金额: $ 40.87万
• 依托单位: WELLESLEY COLLEGE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-06 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10358332
• 关键词: Affect; Allergic; Area; Asthma; Atopic Dermatitis; Bacteria; Bacterial Genes; Bacteroides; Behavior; Bifidobacterium; Biological Assay; Birth; Breast Feeding; Breastfed infant; Child; Conflict (Psychology); Cross-Sectional Studies; Developed Countries; Development; Diet; Diet therapy; Disease; Eczema; Education; Effectiveness of Interventions; Enzymes; Family; Food Hypersensitivity; Frustration; Genes; Genetic Variation; Genomics; Geography; Goals; Health; High Prevalence; Human; Human Milk; Hypersensitivity; Immune System Diseases; Immune system; Incidence; Infant; Inflammatory; Intervention; Intestines; Knowledge; Lactobacillus; Life; Link; Low Prevalence; Measures; Medical; Metabolic; Metabolism; Metagenomics; Methods; Midwestern United States; Modeling; Multiomic Data; Observational Study; Oligosaccharides; Organism; Outcome; Parents; Pattern; Polysaccharides; Population; Prevalence; Prevention Protocols; Probability; Probiotics; Quantitative Reverse Transcriptase PCR; Regimen; Reporting; Research; Risk; Role; Shotguns; Structure; Taxonomy; Treatment Efficacy; United States; Woman; atopy; cohort; effective therapy; feeding; geographic difference; gut microbiome; gut microbiota; immunoregulation; improved; infancy; infant gut microbiome; metagenomic sequencing; microbial; microbiota; prevent; probiotic therapy; protective effect; protective factors; skin disorder; stem; stool sample

DIVERSITY OF HUMAN MILK OLIGOSACCHARIDE METABOLIZING GENES IN TWO INFANT COHORTS Project Summary Atopic dermatitis/eczema is a growing problem in the United States and affects nearly 20% of infants. It usually begins during the first six months of an infant’s life. Early atopy is also one of the predictors of later allergic or other hyperinflammatory health problems. Observational studies have demonstrated a protective effect of human milk feeding for atopic dermatitis/eczema in infants. Thus, to protect their child from this disease, some women choose to feed their infants human milk. However, there is conflicting evidence on the effectiveness of this intervention. Although diet is likely an important contributor to this disease, the composition of the microbiota and its ability to digest a specific component of the diet is potentially just as important in protecting against atopic dermatitis/eczema. In fact, the ability of the intestinal microbiota to metabolize specific human milk oligosaccharides (HMOs) may explain why human milk feeding protects against atopic dermatitis/eczema in some but not all infants fed human milk. In this project, we will investigate microbial metabolism and metabolic products and identify their association to atopic dermatitis. More specifically, we will assess the taxonomic, functional, and metabolic composition of gut-resident bacteria from hundreds of infants residing in the Midwest or Northeast United States to determine the diversity, prevalence, and abundance of microbial HMO metabolism. This multi-omic data will be linked to reports of atopic dermatitis/eczema in the respective infants. We may also identify microbiota-associated genes or metabolites that are protective against atopic dermatitis/eczema. We expect that infants with a more diverse repertoire of HMO metabolizing genes present in their gut microbiome will be protected from atopic dermatitis/eczema. Performing this research in two different regions of the US will be especially advantageous, since subtle differences in medical or cultural practices, or simply geographic differences in microbial exposure, may alter HMO metabolizing gene repertoires independent of breastfeeding behavior. This research will dramatically improve our understanding of microbial HMO metabolism in human infants in the United States and determine whether a specific pattern of HMO metabolizing genes protects infants from atopic dermatitis and eczema.

人乳寡糖代谢基因在两个婴儿队列中的多样性 项目摘要 特应性皮炎/湿疹在美国是一个日益严重的问题，影响到近20%的婴儿。它通常是 开始于婴儿生命的前六个月。早期的特应性反应也是以后过敏或 其他高度炎症性健康问题。观察研究证实了人类的一种保护作用 母乳喂养治疗婴幼儿特应性皮炎/湿疹因此，为了保护自己的孩子免受这种疾病的侵袭，一些妇女 选择给婴儿喂奶。然而，关于这种做法的有效性，有相互矛盾的证据。 干预。尽管饮食可能是导致这种疾病的重要因素，但微生物区系的组成和 它消化饮食中特定成分的能力在预防特应性疾病方面潜在地同样重要 皮炎/湿疹。事实上，肠道微生物群代谢特定人类乳汁的能力 寡糖(HMOS)可以解释为什么母乳喂养可以预防特应性皮炎/湿疹 一些但不是所有的婴儿都喂了母乳。在这个项目中，我们将研究微生物的代谢和代谢 并确定它们与特应性皮炎的关系。更具体地说，我们将评估分类学， 居住在中西部的数百名婴儿肠道细菌的功能和代谢组成 或美国东北部，以确定微生物HMO代谢的多样性、流行率和丰度。 这一多组数据将与相应婴儿特应性皮炎/湿疹的报告联系起来。我们也可能 确定与微生物区系相关的基因或代谢物，它们对特应性皮炎/湿疹具有保护作用。我们 预计肠道微生物群中存在更多样化的HMO代谢基因的婴儿 可预防特应性皮炎/湿疹。在美国两个不同的地区进行这项研究将 尤其有利，因为医疗或文化实践中的细微差异，或者仅仅是地理上的差异 微生物暴露的差异，可能会改变独立于母乳喂养的HMO代谢基因谱系 行为。这项研究将极大地提高我们对人体内微生物HMO代谢的理解。 并确定HMO代谢基因的特定模式是否会保护婴儿 由特应性皮炎和湿疹引起。