Maternal health is emerging as a critical long-term determinant of a child?s health. Therefore, promoting the health of women, especially pregnant women, promotes the well-being of children. The prevalence of gestational diabetes mellitus (GDM) has been steadily increasing, with current estimates at 13%. GDM is associated with adverse outcomes for both the mother and child. For example, there is an increased risk of pre-eclampsia and cesarean section for the mother and hypoglycemia, mental retardation, and birth trauma for the child. GDM has also been associated with an increased risk of future adolescent obesity for the child. Additionally, it has been found that GDM alters the maternal microbiomes, although the extent to which it impacts each ecological niche remains contested. Therefore, it is important to study the impact of GDM on the maternal microbiome to fully understand the impact of GDM at the metagenomic level. Furthermore, because there is intergenerational transfer of microbiomes and the microbiome is an important health determinant, studying the impact of GDM on the acquisition and development of the infant microbiome is critical to understanding risk for oral diseases. In the present proposal, it is hypothesized that the establishment of a stable, personalized infant oral microbiome is significantly influenced by maternal GDM and that the effects of GDM outweigh simple vertical transmission of the microbiome due to shared genetics between mothers and infants. This will be achieved by combining two independent yet integrated study designs with whole genome shotgun sequencing and strain-resolved comparative metagenomics. Both cross sectional and longitudinal study designs will be used to determine whether GDM impacts the oral microbiome, to determine the impact of maternal GDM on the developing infant oral microbiome, and to determine the relative attributions of vertical transmission and GDM to the developing infant oral microbiome. This will reveal the complexity and function of the microbiome at the gene level, stability over time and in response to perturbations, and to what extent the oral microbiome is a heritable feature, similar to the human genome. These findings will have major implications for disease and health including possible determinants of disease susceptibility, risk assessment and feasibility of strategies for prebiotics.
Gestational diabetes mellitus (GDM), defined as glucose intolerance during pregnancy, affects over 13% of pregnant Americans. The proposed studies will reveal the extent to which maternal GDM increases risk for acquisition for pathogens in the infant microbiome, and therefore increase the susceptibility to disease. These findings will have major implications for oral health diseases because both obesity and diabetes, potential adverse outcomes of GDM, are implicated as risk factors for oral diseases such as periodontitis, caries, and oral cancer.
