Maternal obesity alters human milk oligosaccharides content and correlates with early acquisition of late colonizers in the neonatal gut microbiome

Metabolic and immune development in neonates are shaped by the succession of the gut microbiome. Maternal obesity can perturb this process by altering interactions of human milk bioactive elements, including oligosaccharides (HMOs), microbial populations, and metabolites. We conducted a longitudinal study of Mexican mother-infant dyads to examine maternal BMI-associated variations in HMOs and infant fecal microbiota. Breastmilk samples from 97 mothers were collected at 48 h, one month, and three months postpartum. We used targeted and untargeted metabolomics to profile breastmilk samples, while shotgun metagenomics was used to analyze infant fecal microbiome composition in a subset of samples. Mothers with obesity showed decreased concentration of key HMOs shortly after birth, correlating with an altered succession of their infant's gut microbiota. This included reduced early colonizers (Enterobacteriaceae) and increased abundance of intermediate and late colonizers (<i>Bifidobacterium</i> and members of the Lachnospiraceae family), over subsequent months. These taxa negatively correlated with HMOs such as 6'SL, LNnT, and LNT. Additionally, functional profiling revealed alterations in metabolic pathways related to polyamine biosynthesis, suggesting changes in microbial metabolism linked to maternal BMI. Despite the cohort's size, our study offers unique insights into the relationship between maternal obesity, HMO composition, and early infant microbial colonization in Latin-American mothers. This exploratory research serves as proof of concept, underscoring the need for larger-scale studies to validate these findings and better understand their implications for infant health. More importantly, our results highlight the interplay between maternal BMI and human milk bioactives, underscoring the importance of correlating microbial succession with maternal metabolic health to better understand early immune development in neonates.