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: 10113599
• 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 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10113599
• 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; dietary; 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; rapid weight gain; 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 生命第一年的成长轨迹在以后的风险中起着重要作用 超重和肥胖节目。但是，了解什么的知识存在根本的差距 应向婴儿和幼儿提供饮食建议，以促进最佳增长， 防止体重快速增加并降低超重的风险。申请人K01的发现 项目表明，婴儿食用的常见富含蛋白质的食物对 增长和超重风险。具体而言，食用基于乳制品的固体食物的婴儿有 与食用基于肉类固体的婴儿相比，超重的风险显着增加 食物。干预完成后一年，这种增长模式也持续了 表明早期婴儿对生长的长期影响。但是，基础 富含蛋白质的食物与婴儿生长轨迹之间的机制尚未确定。 确定和理解关联饮食和婴儿生长的潜在介体对 实施成功的干预措施，以防止不希望的增长模式。初步的 申请人的K01项目的发现表明，肉与乳制品诱发了差异 肠道菌群的反应。这些微生物群的差异也与 观察到的生长模式。利用申请人K01的粪便样品，该R03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 菌群生长。将评估小鼠长度，身体成分和肠道菌群 纵向四个星期。中心假设是饮食（肉与乳制品） 肠道菌群介导了K01婴儿队列中引起的不同生长模式。 这种效果将在用肉类的粪便样品定居的无细菌小鼠中证明 vs.乳制品小组婴儿。该项目将扩大申请人当前的K01研究范围 包括无菌小鼠模型，这是微生物组研究中的关键组成部分。申请人的 随后的NIDDK R01项目将提议纵向监视增长轨迹，包括 在大量健康的美国队列中，超重和肠道微生物群的风险和肠道菌群的风险 婴儿。收集的数据将支持美国的肠道菌群成熟模型建设， 包括全面的潜在变量，可能会影响增长和 肠道微生物群（母亲/父亲人口统计学，饮食，药物使用等）。它也会有 NIDDK最近发布了特别的利息通知（NOT-DK-19-- 007）确定肥胖发展的危险因素24个月。