Associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome differ according to delivery mode.

BACKGROUND: Mother-to-newborn transmission of obesity-associated microbiota may be modified by delivery mode. Prospective data to test this hypothesis are still sparse. OBJECTIVE: To examine prospective associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome by delivery-mode strata. SUBJECTS/METHODS: In 335 mother-infant pairs in the New Hampshire Birth Cohort, we ascertained data from questionnaires and medical records, and generated microbiome data from 6-week-old infants’ stool using Illumina 16S rRNA gene sequencing (V4-V5 region). Analyses were stratified by delivery mode and conducted before and after adjusting for potential confounders, which included maternal age, education, parity, and Mediterranean diet score. RESULTS: Among 335 mothers, 56% had normal pre-pregnancy BMI (<25, referent), 27% were overweight (BMI 25.1–30), and 18% obese (BMI >30). Among the 312 mothers with weight gain data, 10% had inadequate weight gain, 30% adequate (referent), and 60% excess. In the vaginal-delivery group, maternal overweight or obesity was associated with higher infant gut microbiome diversity and higher abundance of 15 operational taxonomic units (OTUs), including overrepresentation of Bacteroides fragilis, Escherichia coli, Veillonella dispar and OTUs in the genera Staphylococcus and Enterococcus. Delivery mode modified associations of pre-pregnancy BMI with several genera, including the most abundant genus, Bacteroides (P for interaction = 0.05). In the Cesarean-delivered group, there were no significant associations between pre-pregnancy BMI, or gestational weight gain categories with infant microbiome (alpha) diversity or OTUs. CONCLUSIONS: Among vaginally-delivered infants, maternal overweight and obesity was associated with altered infant gut microbiome composition and higher diversity. These associations were not observed in Cesarean-delivered infants, whose microbiome development, we have shown, differs from vaginally-delivered infants. Our study provides additional evidence of delivery-mode dependent associations of maternal weight status with the infant gut microbiota. The role of these associations in mediating the intergenerational cycle of obesity warrants further examination.