The overall objective of this project is to establish how infant diet with different protein-rich foods regulate growth trajectories and gut microbiota development. Both NIH and USDA are now addressing the urgent need for evidence-based dietary guidance early in life, particularly regarding protein intake, but a significant knowledge gap exists in the effects of protein-rich foods on growth and development during early complementary feeding. Early complementary feeding (~5 to 12 months of age), when infants start to consume foods beyond breastmilk or formula, is a critical transition period of developmental plasticity. Growth trajectories and shifts of the gut microbiota during this critical period have the potential to program long-term body weight, composition and disease risks and are greatly influenced by diet. Preliminary data from our pilot study in formula-fed infants demonstrated that consuming diets with two protein-rich foods: meat and dairy at a high-intake level, resulted in distinctive growth patterns from 5 to 12 months of age. An important new preliminary finding was that meat- and dairy-based foods directly affected gut microbiota diversity, composition and short-chain fatty acid production at 12 months. Changes in gut microbiota composition were also associated with infant linear growth (length gain). Here we propose three specific aims to determine how the introduction of common protein-rich foods impact infant growth (Aim 1), the development of gut microbiota (Aim 2) and the relationship between gut microbiota and infant growth (Aim 3), in a randomized controlled trial. Healthy, term infants (n=300) will be recruited and randomized to meat-, dairy-, plant-based diet groups or the reference group (standard of care), from 5 to 12 months. We will use controlled feeding (all foods provided, and formula if needed) with longitudinal assessments of gut microbiota, infant growth, blood biomarkers (IGF-1, IGFBP3, insulin, amino acids, lipids, etc.), dietary intakes, body composition, and total energy expenditure. Our multi-disciplinary team is ideally positioned to conduct this project, with collective expertise in pediatric nutrition, human clinical trials, microbiome, biostatistics, and a long-standing record of collaboration. Findings are expected to have significant scientific and health implications for determining dietary patterns that promote optimal infant growth and identifying gut microbial changes that are beneficial to the host metabolism and growth during early complementary feeding. The results of the study will also support evidence-based dietary recommendations in infants to prevent the risk of overweight and later obesity.