Maternal influences on infant gut microbiome and health.

The establishment of the infant gut microbiome is critical for later health 1,2 , yet how it is shaped by maternal and early-life factors remains unclear. Here we metagenomically sequenced 4,526 longitudinal faecal samples from 714 mother-infant pairs in the Dutch birth cohort Lifelines NEXT, spanning 12 weeks of pregnancy to 1 year postpartum. We integrated these data with 474 clinical and exposure variables, and with ultra-deep sequencing of breast milk and vaginal microbiomes. We observe that the maternal gut microbiome undergoes only subtle changes during pregnancy and postpartum, influenced by diet, infections and pre-pregnancy smoking. The maternal gut microbiome is a major reservoir for infant gut strains, with only occasional transmission from vaginal and breast milk microbiomes. Mother-infant gut strain sharing is time dependent, and higher maternal gut species abundance increases the likelihood of strain transmission. We find that the maternal gut microbiome is a predictor of infant eczema. Mode of delivery and feeding mode primarily shaped the infant gut microbiome and its functional profiles, with maternal exposures also having a role. Of 585 vaginally delivered infants, 155 were born at home, but home delivery was only moderately associated with infant gut microbiome composition, similar to other birth parameters such as duration of pushing and ruptured membranes. Overall, we highlight the central role of the mother and her microbiome in shaping the infant gut ecosystem and early health outcomes.