Perfluoroalkyl Substances and the Gut Microbiome and Fecal Metabolome: Implications for Obesity Risk in Hispanic Children

全氟烷基物质与肠道微生物组和粪便代谢组：对西班牙裔儿童肥胖风险的影响

• 批准号: 10634925
• 负责人: Tanya Lynn Alderete
• 金额: $ 67.23万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634925
• 关键词: 2 year old; Actinomyces; Adult; Age; Age Months; Amino Acids; Archives; Bacteria; Bacteroides; Bile Acids; Biological; Blood; Body mass index; Breast Cancer Detection; Breast Feeding; California; Canada; Cardiovascular Diseases; Cardiovascular system; Chemicals; Child; Childhood; Data; Development; Disease; Dryness; Event; Excretory function; Exposure to; Feeding behaviors; Funding; Future; Goals; Growth; Hispanic; Hispanic Populations; Human; Human Milk; Infant; Intervention; Lactation; Lactobacillus; Life; Link; Lipids; Literature; Longitudinal Studies; Maternal Health; Measures; Metabolic Pathway; Metabolic syndrome; Metagenomics; Milk; Minority Groups; Modality; Mothers; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obesity Epidemic; Physical activity; Poly-fluoroalkyl substances; Predisposition; Pregnancy; Preventive measure; Probiotics; Production; Reporting; Research; Research Personnel; Risk; Sampling; Source; Spottings; Subgroup; Testing; Unhealthy Diet; United States National Institutes of Health; Volatile Fatty Acids; Weight; Youth; bile acid metabolism; cohort; comorbidity; critical period; drinking water; early life exposure; early-onset obesity; energy balance; environmental chemical; experimental study; exposed human population; fatty liver disease; fecal metabolome; gut bacteria; gut microbiome; gut microbiota; high risk; improved; infancy; infant gut microbiome; insight; lipid biosynthesis; metabolomics; microbial; multidisciplinary; multiple omics; novel; obesity in children; obesity prevention; obesity risk; obesity treatment; obesogenic; physical inactivity; postnatal; prenatal; prenatal exposure; prevent; public health priorities; rapid growth; rapid infant weight gain; screening; stool sample; transmission process; underserved community

ABSTRACT Childhood obesity is a high priority public health issue as it increases the risk of co-morbid diseases, including cardiovascular disease, fatty liver disease, and type 2 diabetes. An improved understanding of the factors that trigger the development of early life obesity is urgently needed. This is especially important among Hispanics, a minority group with high rates of obesity in early life. Beyond poor diet and a lack of physical activity, early life exposure to environmental chemicals, which are higher in underserved communities, independently contribute to childhood obesity. Human studies show that even at low levels of exposure during pregnancy, poly- and perfluoroalkyl substances (PFAS) are associated with rapid infant weight gain and greater risk for childhood obesity. Postnatally, breastfeeding is a primary source of inadvertent PFAS transmission to infants, potentially offsetting some benefits of extended breastfeeding. Recent findings suggest that the developing gut microbiome is exposed to breast milk PFAS, which may alter gut bacteria and fecal metabolites that contribute to obesity. Despite this, human studies have largely focused on prenatal PFAS exposure, and no prior studies have examined the effects of breast milk PFAS on rapid infant growth and the gut microbiome during infancy, a critical period in which interventions have the potential to prevent the development of childhood obesity. Our overarching hypothesis is that higher concentrations of breast milk PFAS contribute to more rapid infant growth and childhood obesity risk, and that these effects are explained by alterations in the composition and function of the infant gut microbiome. This hypothesis is based on results from our preliminary data, which demonstrate that infant gut bacteria are associated with infant weight and breast milk PFAS at 6-months of age. Our multidisciplinary team of investigators propose to test this hypothesis in a cohort of 208 Hispanic mother-child pairs with assessments of child growth at 1, 6, 12, 18, 24, and 36-months as well as at 6yr of age. This study will measure breast milk PFAS concentrations and characterize the infant gut microbiome and fecal metabolome using archived breast milk and stool samples at 1- and 6-months to advance our mechanistic understanding of the obesogenic effects of PFAS exposure while accounting for prenatal PFAS exposure using newborn dried blood spots. Our aims are to determine the extent to which early life exposure to breast milk PFAS are associated with: 1) child weight from 1-month to 6 years (Aim 1A) and the risk of rapid growth and childhood obesity (Aim 1B) as well as 2) changes in gut microbial profiles and fecal metabolites (Aim 2). Our ultimate goal (Aim 3) is to integrate breast milk PFAS exposure, gut microbiome, and fecal metabolomics profiles to identify subgroups of children that are at increased risk for rapid growth and obesity. This study offers a unique opportunity to advance our understanding of breast milk PFAS and may identify preventive measures that could be used to offset obesity-risk, including screening for breast milk PFAS and the use of probiotics to promote growth of beneficial gut bacteria in early life.

摘要 儿童肥胖是一个高度优先的公共卫生问题，因为它增加了合并疾病的风险，包括 心血管疾病、脂肪肝和2型糖尿病。对以下因素的更好理解 引发早期生活肥胖的发展是迫切需要的。这在拉美裔中尤其重要， 早期肥胖率高的少数群体。除了糟糕的饮食和缺乏体力活动，早期生活 暴露于环境化学品，这在服务不足的社区中更高，独立地起到了作用 儿童肥胖症。人体研究表明，即使在怀孕期间暴露于低水平的环境中，多聚体和 全氟烷基物质(PFAS)与婴儿体重快速增加和儿童风险增加有关 肥胖。在出生后，母乳喂养是婴儿无意中传播PFAS的主要来源，可能 抵消了延长母乳喂养的一些好处。最近的发现表明，发育中的肠道微生物群 暴露在母乳中的全氟辛烷磺酸可能会改变导致肥胖的肠道细菌和粪便代谢物。 尽管如此，人类研究主要集中在产前接触全氟辛烷磺酸，以前的研究没有。 研究了母乳全氟辛烷磺酸对婴儿快速生长和婴儿期肠道微生物群的影响，这是一个关键的 干预措施有可能预防儿童肥胖发展的时期。我们最重要的是 假说是母乳中全氟辛烷磺酸浓度较高有助于更快的婴儿生长和儿童时期。 肥胖风险，这些影响是通过婴儿肠道组成和功能的变化来解释的 微生物组。这一假设是基于我们初步数据的结果，这些数据表明婴儿的肠道 细菌与婴儿体重和6个月大的母乳全氟辛烷磺酸有关。我们的多学科团队 的研究人员建议对208对西班牙裔母子进行评估，以检验这一假设 儿童在1、6、12、18、24和36个月以及6岁时的生长发育。这项研究将测量母乳 利用存档乳房测定婴儿肠道微生物组和粪便代谢组的PFAS浓度和特征 在1个月和6个月时采集牛奶和粪便样本，以促进我们对肥胖影响的机制理解 使用新生儿干血斑点对全氟辛烷磺酸暴露的影响，同时考虑产前全氟辛烷磺酸暴露。我们的目标是 为了确定早期接触母乳全氟辛烷磺酸的程度与：1)儿童体重来自 1个月至6岁(目标1A)和快速增长和儿童肥胖的风险(目标1B)以及2)变化 肠道微生物谱和粪便代谢物(目标2)。我们的最终目标(目标3)是整合母乳PFAS 暴露、肠道微生物组和粪便代谢组学特征以确定儿童增加的亚组 有快速增长和肥胖的风险。这项研究提供了一个独特的机会来促进我们对乳房的理解 牛奶PFAS，并可能确定可用于抵消肥胖风险的预防措施，包括筛查 对于母乳全氟辛烷磺酸和使用益生菌，以促进有益的肠道细菌在生命早期的生长。