Impact of Sugars and Human Milk Oligosaccharides on Infant Microbiome and Obesity

糖和人乳寡聚肽对婴儿微生物组和肥胖的影响 摘要 西班牙裔儿童患肥胖症的风险很高，这种差异在2岁时就已经存在。我们事先 研究发现，早期的高糖饮食会增加这种风险， 在接触延长（非纯母乳喂养）母乳喂养> 12个月的儿童中消失。因此，在本发明中， 糖和延长母乳喂养对早期肥胖风险产生相反的影响，但其机制是 不清楚饮食中的糖和延长母乳喂养可能影响婴儿肥胖风险的一种方式是 影响肠道微生物组的发育，这是在生命的前24个月迅速演变。这是一 考虑到肠道微生物组与肥胖的发展有关， 微生物的变化已被记录在对母乳中的膳食糖和因子的反应中。一个因素 母乳中可能直接相关的是不同母乳低聚糖（HMO）的混合物， 它们完整地到达结肠并作为益生元，形成肠道微生物群的多样性。因此 HMO对微生物组发育的影响可能是母乳喂养保护 这是一个新的概念，得到了我们初步数据的支持。暴露于高糖饮食 也可能通过扰乱认知功能和食欲调节来影响肥胖风险， 这表明这些作用也可能是由肠道微生物介导的，HMO可以防止 这些缺陷，但缺乏人类研究。我们建议在一项队列研究中检查这些概念， 240名西班牙裔妇女和她们的新生儿。参与者将从出生到24个月进行随访， 经常对母乳进行HMO成分、母婴微生物群的采样和评估， 母婴饮食和婴儿饮食行为。主要结果将是DEXA测定的婴儿体脂， 次要结果将是婴儿认知和食欲调节，包括肠源性食欲激素 在子集中。我们有4个具体目标：1）确定膳食糖和HMO的联合作用， 婴儿肠道微生物组的发展; 2）确定膳食糖和HMO对婴儿肠道微生物组的联合影响。 婴儿身体脂肪的发展。3)确定膳食糖和HMO对婴儿认知能力的联合影响 结果，饮食行为和食欲调节;以及4）确定膳食糖和 HMO对婴儿结局的影响由肠道微生物组的变化介导。这项研究将推动该领域 通过确定早期生活饮食暴露（重点是膳食糖，母乳喂养和HMO） 影响肠道微生物组的发育，以及这如何影响肥胖，认知和食欲的发展 调控研究结果预计将对确定特定的HMO和/或肠道 微生物的变化将对肥胖起到保护作用，并为未来适用的新型干预方式提供信息。 西班牙裔妇女和她们的婴儿。

Impact of Sugars and Human Milk Oligosaccharides on Infant Microbiome and Obesity Abstract Hispanic children are at high risk for obesity, a disparity that is already established by 2 years of age. Our prior work found that high dietary sugars in early-life contributes to this increased risk and that this adverse effect was obliterated in children who were exposed to extended (not exclusive) breastfeeding for >12 months. Thus, sugars and extended breastfeeding exert opposing effects on early obesity-risk, but the mechanisms are unclear. One way that dietary sugars and extended breastfeeding could impact infants’ obesity-risk is by affecting gut microbiome development, which is rapidly evolving during the first 24 months of life. This is a plausible mechanism given that the gut microbiome is implicated in the development of obesity, and that gut microbial changes have been documented in response to dietary sugars and factors in breast milk. One factor in breast milk that may be directly relevant is the mixture of different human milk oligosaccharides (HMOs), which reach the colon intact and serve as prebiotics, shaping the diversity of the gut microbiota. Therefore, the effects of HMOs on microbiome development could be one mechanism by which breastfeeding protects against obesity in infants, a novel concept supported by our preliminary data. Exposure to high dietary sugars in infancy could also impact obesity risk by disrupting cognitive function and appetite regulation, and evidence suggests that these effects might also be mediated by the gut microbiome, and that HMOs, can protect against these impairments, but human studies are lacking. We propose to examine these concepts in a cohort study in 240 Hispanic women and their newborn infants. Participants will be followed from birth to 24 months, with frequent sampling and assessment of breast milk for HMO composition, maternal and infant microbiota, maternal and infant diet, and infant eating behaviors. The primary outcome will be infant body fat by DEXA and secondary outcomes will be infant cognition and appetite regulation, including gut-derived appetite hormones in a sub-set. We have 4 Specific Aims: 1) Determine the joint effects of dietary sugars and HMOs on development of the infant gut microbiome; 2) Determine the joint effects of dietary sugars and HMOs on development of infant body fat.; 3) Determine the joint effects of dietary sugars and HMOs on infant cognitive outcomes, eating behavior and appetite regulation; and 4) Determine whether the effects of dietary sugars and HMOs on infant outcomes are mediated by changes in the gut microbiome. This study will move the field forward by identifying how early-life dietary exposures (focusing on dietary sugars, breastfeeding and HMOs) affect gut microbiome development, and how this affects development of obesity, cognition and appetite regulation. Findings are expected to have significant implications for identifying specific HMOs and/or gut microbial changes that will be protective for obesity and inform future novel intervention modalities applicable to Hispanic women and their infants.