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

使用无菌小鼠阐明肠道微生物群对婴儿生长和体重增加的影响

• 批准号: 9895410
• 负责人: Minghua Tang
• 金额: $ 11.66万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-24 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895410
• 关键词: 16S ribosomal RNA sequencing; Affect; Age-Months; Attention; Birth; Body Composition; Body fat; Calories; Collection; Consumption; Data; Diet; Dietary intake; Energy Intake; Etiology; Food; Future; Germ-Free; Growth; Human; Impairment; Infant; Infant Food; Intervention; Investigation; Knowledge; Length; Life; Link; Meat; Mediating; Mediator of activation protein; Metabolic Diseases; Metabolism; Mission; Modeling; Monitor; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Overweight; Pattern; Pharmaceutical Preparations; Phenotype; Play; Prevention; Proteins; Public Health; Randomized; Recommendation; Research; Risk; Risk Factors; Role; Ruminococcus; Solid; Source; Structure; Toddler; United States National Institutes of Health; Volatile Fatty Acids; Weight; Weight Gain; base; cohort; demographics; feeding; gut microbiota; human disease; infancy; interest; link protein; metabolomics; microbial; microbiome research; microbiota; model building; modifiable risk; mouse model; nutrition; obesity development; prevent; programs; protein intake; response; stool sample; successful intervention

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.

抽象的 生命第一年的生长轨迹对以后的风险起着重要作用 超重和肥胖规划。然而，对于什么是知识，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， 防止体重快速增加并降低超重的风险。申请人 K01 的调查结果 项目表明，婴儿食用的常见富含蛋白质的食物对 生长和超重的风险。具体来说，食用乳制品固体食物的婴儿 与食用肉类固体食物的婴儿相比，超重的风险显着增加 食物。这种增长模式在干预完成一年后也持续存在， 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。 识别和了解连接饮食和婴儿生长的潜在调节因素对于 实施可以防止不良增长模式的成功干预措施。初步的 申请人的 K01 项目的研究结果表明，肉类与乳制品引起的差异 肠道微生物群的反应。这些微生物群差异也与 观察到的生长模式。该R03项目利用申请人K01的粪便样本 将使用活跃生长的无菌小鼠来直接评估肠道的潜在影响 微生物群对生长的影响。将评估小鼠的长度、身体成分和肠道微生物群 纵向持续四个星期。中心假设是饮食（肉类与乳制品为主） 在 K01 婴儿群体中诱导不同的生长模式是由肠道微生物群介导的； 这种效果将在被肉粪便样本定植的无菌小鼠中得到证实 与乳制品组婴儿相比。该项目将扩大申请人目前的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 项目将建议纵向监测增长轨迹，包括 美国健康人群从出生到 24 个月的超重风险和肠道微生物群 婴儿。收集的数据将支持美国肠道微生物群成熟模型的构建， 包括可能影响增长和经济增长的潜在变量的全面集合 肠道微生物群（母亲/父亲人口统计、饮食、药物使用等）。它还会有 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) 识别出生至 24 个月期间肥胖发展的危险因素。