Human Milk Leptin, Insulin and N6/N3 Fatty Acids are associated with Early Differences in Gut Microbiome of Infants Born to Normal Weight and Obese Mothers

BACKGROUND: Obese mothers deliver offspring with greater risk of developing childhood obesity and the gut microbiome may be an important factor mediating this relationship during infancy. OBJECTIVE: Determine how exposure to human milk (HM) components are associated with the structure and function of infants' gut microbiome delivered to mothers with high vs. low pre-pregnancy BMI. METHODS: Microbiota was determined from vaginally delivered exclusively breastfed full-term infant stool samples using targeted 16S gene and whole-genome shotgun sequencing. Insulin, leptin, total n-6 and n-3 fatty acids in fasting mid-feed HM was measured by GC-MS. RESULTS: Taxa and metagenomes of the infant microbiome did not differ based on maternal BMI. HM insulin, leptin and n-6/n-3 fatty acid ratio were positively associated (p<0.01) with maternal BMI. Adjusting for maternal BMI, HM leptin was associated with Firmicutes (p=0.03) and Flavin adenine dinucleotide biosynthesis pathway (p=0.04). HM insulin was associated with A...