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

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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.