Elucidating the effect of the gut microbiota on infant growth and weight gain using germ-free mice

摘要 生命第一年的生长轨迹在以后的风险中起着重要的作用 超重和肥胖规划。然而，在了解什么方面存在着根本的差距 应该向婴幼儿提供饮食建议，以促进最佳生长， 防止体重快速增加，降低超重的风险。申请人的K01调查结果 项目显示，婴儿食用的常见富含蛋白质的食物对 增长和超重风险。具体地说，食用以乳制品为基础的固体食物的婴儿 与食用肉基固体食品的婴儿相比，超重风险显著增加 食物。在干预结束一年后，这种增长模式也持续了下来， 这表明了早期婴儿喂养对生长的长期影响。然而，潜在的 富含蛋白质的食物和婴儿生长轨迹之间的机制尚未确定。 确定和了解饮食和婴儿生长发育之间的潜在中介对于 实施成功的干预措施，防止不受欢迎的增长模式。初步 申请者的K01项目的研究结果表明，肉类和乳制品会导致差异 肠道微生物区系的反应。这些微生物区系的差异也与 观察到的生长模式。利用申请人的K01的粪便样本，这个R03项目 将使用活跃生长的无菌小鼠直接评估肠道的潜在影响 微生物区系在生长。将评估小鼠的长度、身体组成和肠道微生物区系 纵向上持续了四周。中心假设是饮食(以肉类为主，而不是以奶制品为主) 在K01‘S婴幼儿群体中诱导的不同生长模式是由肠道微生物区系介导的； 这一效应将在无菌小鼠身上得到证实，这些小鼠的粪便样本来自肉类。 与奶制品组婴儿的对比。该项目将扩大申请者目前的K01研究范围 包括无菌小鼠模型，这是微生物组研究的关键组成部分。申请人的 后续的NIDDK R01项目将建议纵向监控增长轨迹，包括 在一大批健康的美国人中，超重的风险和从出生到24个月的肠道微生物群。 婴儿。收集的数据将支持美国的肠道微生物区系成熟模型的建立， 包括全面收集可能影响增长和经济增长的潜在变量 肠道微生物区系(母亲/父亲的人口统计、饮食、药物使用等)。它还将拥有 重大计划相关性，因为NIDDK最近发布了特别兴趣通知(非-DK-19- 007)确定出生至24个月肥胖的风险因素。

ABSTRACT Growth trajectories during the first year of life play an important role in later risk of overweight and obesity programming. However, there is a fundamental gap in knowledge of what dietary recommendations should be provided to infants and toddlers to promote optimal growth, prevent rapid weight gain and reduce the risk of overweight. Findings from the applicant’s K01 project showed that common protein-rich foods that infants consume have a significant impact on growth and risk of overweight. Specifically, infants who consumed dairy-based solid foods had significantly increased risk of overweight, compared with infants who consumed meat-based solid foods. This growth pattern also persisted one year after the intervention was completed, suggesting the long-term impact of early infant feeding on growth. However, the underlying mechanisms between protein-rich foods and infant growth trajectories are yet to be determined. Identifying and understanding the potential mediators linking diet and infant growth is critical to implementing successful interventions that could prevent undesired growth patterns. Preliminary findings from the applicant’s K01 project showed that meat vs. dairy foods induced differential responses of the gut microbiota. These microbiota differences are also associated with the observed growth patterns. Utilizing stool samples from the applicant’s K01, this R03 project will use actively growing germ-free mice to directly assess the potential impact of the gut microbiota on growth. Mice length, body composition and the gut microbiota will be assessed longitudinally for four weeks. The central hypothesis is that the diet (meat- vs. dairy-based) induced different growth patterns in the K01’s infant cohort are mediated by the gut microbiota; this effect will be demonstrated in the germ-free mice colonized with stool samples from the meat vs. dairy group infants. This project will expand the applicant’s current K01 research scope by including the germ-free mice model, a critical component in microbiome research. The applicant’s subsequent NIDDK R01 project will propose to longitudinally monitor growth trajectory, including risk of overweight and the gut microbiota from birth to 24 months in a large cohort of healthy U.S. infants. Data collected will support the U.S. based gut microbiota maturation model building, including a comprehensive collection of potential variables that may affect both growth and the gut microbiota (maternal/paternal demographics, diet, medication use, etc). It will also have significant program relevance as NIDDK recently posted the special interest notice (NOT-DK-19- 007) identifying birth to 24 months risk factors of obesity development.