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

摘要 出生后第一年的生长轨迹在以后的风险中起着重要作用。 超重和肥胖的节目。然而，在知识上存在着根本性的差距， 应向婴儿和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K 01的调查结果 一项研究表明，婴儿食用的常见富含蛋白质的食物对 增长和超重的风险。具体来说，食用乳制品固体食物的婴儿 与食用肉类固体食品的婴儿相比， 食品这种增长模式在干预措施完成一年后仍然存在， 这表明早期婴儿喂养对生长的长期影响。然而，底层 富含蛋白质的食物和婴儿生长轨迹之间的机制尚未确定。 识别和理解联系饮食和婴儿生长的潜在介质对于 实施成功的干预措施，防止出现不受欢迎的增长模式。初步 申请人的K 01项目的结果表明，肉类与乳制品引起的差异 肠道微生物群的反应。这些微生物群的差异也与 观察增长模式。利用来自申请人K 01的粪便样本，该R 03项目 将使用积极生长的无菌小鼠直接评估肠道的潜在影响， 微生物群的生长。将评估小鼠的长度、身体组成和肠道微生物群 纵向四周。核心假设是，饮食（肉类与乳制品为主） 在K 01的婴儿群体中诱导的不同生长模式是由肠道微生物群介导的; 这种效果将在无菌小鼠中得到证实， vs.奶制品组婴儿。该项目将扩大申请人目前的K 01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NIDDK R 01项目将建议纵向监控增长轨迹，包括 超重的风险和肠道微生物群从出生到24个月在一个健康的美国大队列。 婴儿。收集的数据将支持美国肠道微生物群成熟模型的建立， 包括可能影响经济增长和 肠道微生物群（母亲/父亲人口统计学、饮食、药物使用等）。它也将有 重要的计划相关性，因为NIDDK最近发布了特别兴趣通知（NOT-DK-19- 007)确定出生至24个月肥胖发展的危险因素。

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.