Role of the Gut Microbiota in the Increased Infant Body Mass Index Induced by Gestational Diabetes Mellitus

The connection between gestational diabetes mellitus (GDM) and the offspring’s development, such as obesity, is well established. Emerging evidence indicates that the microbiota of the neonate's meconium is associated with maternal GDM status. To explore whether the association between GDM and infant body mass index (BMI) in early childhood is affected by the meconium microbiota, we recruited 120 mothers (60 healthy women and 60 with GDM) and their newborns from the Women’s Hospital of Nanjing Medical University. Meconium of 120 neonates was collected within a few hours after birth and sequenced using 16S rRNA sequencing analysis. Children’s BMI was measured at 12 months of age. The results revealed that infants born to mothers with GDM had increased BMI Z-scores at 12 months old and that the β-diversity of their meconium microbiota was reduced. Several genera were observed to be significantly different between the GDM and control groups. The genus Burkholderia-Caballeronia-Paraburkholderia and an untitled genus in the family Enterobacteriaceae enriched in neonates born to healthy mothers were found to be negatively associated with infant BMI by using regression analysis. A coabundance group depleted in the GDM group was correlated negatively with 12-month BMI and mediated 21.65% of the association between GDM and infant BMI by mediation analyses. This study provided evidence for the associations among maternal GDM, the meconium microbiota, and infant BMI. Maternal GDM was demonstrated to affect infant BMI, mediated by the gut microbiome. Gut microbiome interventions might represent a novel technique to decrease the risk of GDM-induced childhood obesity. IMPORTANCE Using 16S rRNA sequencing analysis, regression analysis and mediation analysis were used to explore whether maternal gestational diabetes mellitus (GDM) changed the function and composition of the meconium microbiota and whether this explained the GDM-induced alterations of infant body mass index (BMI). This study showed that gut microbiome dysbiosis induced by maternal GDM might play an important role in the increased infant BMI during the first 12 months of life. Therefore, gut microbiome interventions might represent a novel technique to decrease the risk of GDM-induced childhood obesity.