Unlocking the power of human milk and infant feeding: Understanding how nutrition and early microbiota interaction shapes health programming

Human milk represents a highly evolved bioactive system that promotes colonization by infant microbial pioneers, supports immune maturation, and fosters infant development. Beyond providing nutrition, human milk contains key bioactive components, such as microbes, metabolites, human milk oligosaccharides, immunoglobulins, lactoferrin, and antimicrobial peptides. These factors influence colonization of the infant gut microbiome and facilitate immune development and metabolic health, with implications for health outcomes and risk of non-communicable diseases. In this review, we highlight the impact of infant feeding, human milk constituents (especially bioactive compounds), and weaning on infant microbial trajectories. By understanding how early-life nutrition influences microbial colonization and nutrient sensing, i.e., “how we feed our microbes,” we can develop targeted interventions and personalized diets to support proper gut maturation and disease prevention from infancy to adulthood, as well as explore the therapeutic potential of human milk bioactives beyond infancy, offering new strategies for disease prevention and treatment.