Infant gut microbiota and SCFAs mediate the association between early-life human milk microbiota and neurodevelopment.

Human milk microbiota (HMM) plays a key role in infant gut microbiota (IGM) establishment, however, the influence of the early life HMM in later neurodevelopment remains unclear. In this mother-infant cohort, we investigated HMM development and its impact on IGM-neurodevelopment crosstalk. Breast milk and infant feces were collected on days 0, 7, and 30 for sequencing and SCFAs quantification, while neurodevelopment was assessed via ASQ-3 at 12 months. HMM remained stable during the first month, while IGM fluctuated significantly within the first 7 days. Songbird and mediation analyses revealed strengthening associations between HMM, IGM, and neurodevelopment over time. IGM served as a key mediator linking HMM to neurodevelopment, with SCFAs playing a mediating role in the connection between IGM and neurodevelopment on day 30. Our findings suggest that early-life stable and unique HMM may influence long-term neurodevelopment by dynamically modulating IGM and SCFAs, highlighting a potential strategy to prevent neurodysplasia by monitoring mother-infant microecology.