J Transl Med. 2026 Aug 31;24(1):1125. doi: 10.1186/s12967-026-08844-1.
ABSTRACT
The first 1000 days of life represent a critical developmental window during which early microbial colonization contributes to immune, metabolic, and neurodevelopmental programming. Human milk is increasingly recognized as a biologically active fluid that shapes infant gut microbiome assembly through microorganisms, human milk oligosaccharides (HMOs), immune factors, and microbial metabolites. Within this framework, the human milk microbiome has emerged as a potential contributor to the milk-gut-brain axis (MGBA), a bidirectional communication network linking the gut microbiota with neural, immune, endocrine, and metabolic pathways involved in brain development. This review summarizes current evidence regarding the origins, determinants, and functional relevance of the human milk microbiome and its potential role in early-life neurodevelopment. Proposed microbial sources include maternal skin, the infant oral cavity, environmental exposure, and the entero-mammary pathway, while key determinants include lactational stage, delivery mode, antibiotic exposure, maternal diet, obesity, and prematurity. Mechanistic pathways linking milk-associated microbes with neurodevelopment are discussed, including microbial colonization, immune and barrier maturation, vagal and neuroendocrine signalling, and production of short-chain fatty acids (SCFAs) and tryptophan-derived metabolites. We further evaluate evidence relating breastfeeding and milk-associated microbial exposures to cognitive, behavioural, and neurodevelopmental outcomes, particularly in preterm and medically vulnerable infants. Although experimental and observational evidence supports biologically plausible links between the human milk microbiome and the developing microbiota-gut-brain axis, major uncertainties remain regarding microbial viability, sustained colonization, causality, and long-term functional significance. Methodological limitations, including low microbial biomass, contamination susceptibility, and heterogeneity in analytical approaches, continue to complicate interpretation across studies. Future progress will require longitudinal, mechanistically informed studies integrating microbiome profiling with metabolomics, immune phenotyping, neuroimaging, and validated neurodevelopmental outcomes.
PMID:42681656 | DOI:10.1186/s12967-026-08844-1
