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

The infant gastrointestinal tract is critical for metabolic and immune development, shaped by early gut microbiome colonization. Maternal obesity may disrupt this process by altering human milk oligosaccharides (HMOs), influencing microbial succession and infant health. This longitudinal study examines maternal BMI-associated variations in HMOs and infant fecal microbiota. Human milk samples from 97 mothers (stratified by BMI) were collected at 48h, one month, and three months postpartum, with HMOs quantified via UPLC-MS/MS. In a subsample of this population, infant fecal microbiome composition was analyzed using metagenomics tools. Mothers with obesity exhibited reduced 2’-FL, LNnT, 3’-SL, 6’-SL, LNFPI concentration at 48 h postpartum. Infants born to these mothers showed diminished early colonizers such as Gammaproteobacteria at 48h, alongside lower antigen and polyamine biosynthesis pathways. Conversely, late colonizers like Lachnospiraceae species were more abundant at one and three months postpartum. Sialylated and neutral HMOs negatively correlated with these late colonizers, which metabolize such oligosaccharides. These findings suggest maternal obesity alters HMO profiles, potentially disrupts pioneer microbial establishment and accelerating late-colonizer dominance. Reduced keystone bacteria and shifted metabolic pathways may impair immune priming, with long-term health implications. This highlights the interplay between maternal BMI, HMO composition, and infant microbiome succession, underscoring the need to address maternal metabolic health to optimize early microbial colonization and immune programming.