Early-Life Protein Nutrition and Enzymatic Regulation: Mechanistic Pathways Linking Growth Faltering, Stunting, and Obesity

Nutrition in the early years has a significant impact on an individual's long-term development patterns and metabolic health via protein intake and enzymatic pathways. The current literature review analyses the coexistence of malnutrition and obesity by associating a shortage of essential amino acids to stunting via impaired mTORC1/IGF-1 signaling, whereas excessive protein intake in early life is linked to accelerated weight gain, increased adiposity, and a heightened risk of insulin resistance. Several molecular mechanisms link these extremes, including AMPK energy sensing, intestinal dysbiosis, and hormonal dysregulation (leptin/ghrelin imbalance). The development of digestive enzymes such as pepsin activation, pancreatic proteases (trypsin week 14–16), lipase (week 21), and brush-border peptidases impacts food absorption, and enzyme deficits aggravate malabsorption in cases of malnutrition. Maternal health status, infections, and exposure to obesogenic diets during the first 1000 days of life significantly increase the risk of impaired gastrointestinal development and nutrient utilization. Integrative interventions like balanced protein formulas, breastfeeding encouragement, lipid-based supplements, malaria management, and enzyme replacement treatments mitigate the negative consequences. Considering the consequences of early dysregulation in cardio-metabolic processes during a lifetime, personalized nutrition and their pathways modulators can play a pivotal role to prevent it.