Comparing early life nutritional sources and human milk feeding practices: personalized and dynamic nutrition supports infant gut microbiome development and immune system maturation.

Exclusive breastfeeding is recommended for the first six months of life, but many infants receive pumped milk, formula, donor human milk, or other nutritional sources during this critical period. Substantive evidence shows early nutrition influences development of the microbiome and immune system, affecting lifelong health. However, the underlying mechanisms are unclear and the nuances of human milk feeding are rarely considered. This review synthesizes evidence from human studies and model systems to discuss the impact of different nutritional sources on co-development of the gut microbiome, antigen tolerance, and immunity. We highlight two key mechanisms: epigenetics and the so-called "weaning reaction". Collectively, this evidence highlights i) the fundamental role of parents' own milk, fed directly at the breast, as a dynamic and personalized nutrition source that drives developmental programming, and ii) the deficiencies of alternative nutritional sources and priority research areas for improving these alternatives when direct breastfeeding is not possible.