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.

M.C.C. acknowledges support from a H2020-ERC Starting Grant (MAMI-639226 project), the Horizon Europe Program (INITIALISE-101094099 project), a Spanish Ministry of Science and Innovation (MCIN) research grant (MAMI+, ref. PID2022-139475OB-I00), and PROMETEO/GVA (Microglocal ref. CIPROM2023/030). M.C.C. would like to acknowledge the award of the Spanish Government MCIN/AEI to the IATA-CSIC as Center of Excellence Accreditation Severo Ochoa (CEX2021-001189-S/MCIN/AEI/10.13039/501100011033). L.J.H. is supported by a Wellcome Trust Investigator Award (220876/Z/20/Z) and the Biotechnology and Biological Sciences Research Council Institute Strategic Programme Food, Microbiome and Health BB/X011054/1 and its constituent project BBS/E/QU/230001B. A.Z. is supported by Netherlands Organization for Scientific Research (NWO) VICI grant VI.C.232.074, NWO Gravitation grant ExposomeNL 024.004.017, NWO KIC grant KICH1.LWV04.21.01, ZonMW ME/CFS grant 10091012110015, the EU Horizon Europe Program grants INITIALISE (101094099), and DarkMatter (“ID-DarkMatter-NCD” [project number 101136582]).

With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001189-S)

Peer reviewed