Supervised Modelling of Longitudinal Human Milk and Infant Gut Microbiome Reveal Maternal Pre-Pregnancy BMI and Early Life Growth Interactions

Maternal obesity is a key risk factor for excessive foetal growth and childhood obesity, yet its influence on human milk (HM) composition and the infant gut microbiome development remains unclear. This study examined 169 mother-infant dyads analyzing 570 HM metabolome, 495 HM microbiome, and 348 infant faecal microbiome samples over three months of exclusive breastfeeding, alongside infant anthropometric data through three years postpartum. While BMI was not directly correlated with infant growth (weight-for-length/height z-score), N-way Partial Least Squares modelling revealed microbial and metabolite signatures linked to maternal ppBMI and infant growth. High maternal ppBMI and infant growth were associated with altered HM oligosaccharides and enrichment of Bifidobacterium spp. in the infant gut. In contrast, elevated HM simple sugars, amino acid derivatives, and gut Klebsiella and Escherichia spp. relative abundance linked to slower growth. These findings highlight maternal-infant nutritional dynamics, informing targeted strategies to support infant growth.