Role of Maternal Breast Milk in the Maturation of the Infant Intestinal Microbiome, Immunity, and the Impact of Pregnancy-Related Complications

The establishment of the microbiome in infants is significantly influenced by maternal-to-offspring microbiota transfer, with breastfeeding playing a pivotal role in introducing novel microbial communities and promoting infant gut microbiome maturation. The content of Breastmilk (BM) changes dynamically in order to meet the evolving demands of the infant at various stages of development. BM contains diverse microbiota that have been shown to vary by gestational age, lactation stage and delivery mode. Our knowledge of the BM microbiota has mostly come from mothers who had healthy pregnancies, potentially limiting its applicability to mothers who experienced pregnancy complications including preterm birth (PTB) and Gestational diabetes Mellitus (GDM). Currently, there is a gap in research pertaining to the comprehensive microbial profiles of BM microbiota associated with GDM. While a few studies have employed high-throughput sequencing methods to explore BM microbiota in mothers of preterm infants, these efforts have been constrained by small sample sizes and variations in postpartum ages during milk collection. Additionally, the intricate relationship between maternal BM microbiota and infant gut bacterial communities remains insufficiently examined. With this study we hypothesize that the BM microbiota plays a pivotal role in seeding and maturing the infant gut microbiota and influencing early immune programming. Pregnancy related complications such as PTB have a significant impact on the composition of the BM microbiota leading to atypical intestinal colonization during the first weeks of life, thereby altering the immunological functions of the infants, increasing their susceptibility to immunological and metabolic diseases. To validate the hypothesis, we selected a sub-cohort of maternal-infant dyads from the Molecular Signatures in Pregnancy study (MSP), encompassing PTB, GDM, and control groups. Maternal BM and infant stool and blood samples were analyzed.

Overall, we observed that the BM samples increased in diversity and relative abundance of lactose-fermenting bacteria as they matured. Staphylococcus and Streptococcus were identified as the core BM genera. Preterm BM samples were compositionally distinct, were high in species richness and were enriched in typical gut commensal. Corynebacterium and Staphylococcus were highly abundant in BM samples of women who had gestational diabetes. Albeit meconium the infant gut microbial communities became increasingly diverse with age and were possibly seeded from different maternal sources including BM in a lactation stage-dependent manner. Streptococcus, Veillonella, lactobacillus were among the top genus shared between maternal BM and infant gut pairs and preterm mothers sa higher percentage of BM genus with their infants as compared to other groups specifically the gut commensals. We also noted age dependent clustering of infant gene expression profiles with peak transcriptional activity at birth. Divergent transcriptional profiles in preterm and term infants at birth converge towards similar patterns by six months of age. BM microbiome correlated with infant transcriptome at higher degree in the control samples as compared to the one with pregnancy-related complications. This research will provide crucial insight on the colonization and early evolution of the human microbiome and immunity.