Abstract
Increasing evidence has suggested that maternal gestational diabetes mellitus (GDM) can influence the neonatal gut microbiota. However, the initial microbial colonization of neonates is still unclear. The discrepancy in results between studies may be due to many other prenatal characteristics. This study aimed to investigate whether perinatal characteristics affect the association between maternal GDM status and early neonatal gut microbiota. This nested case-control study was based on a cohort of mothers and children (2016YFC1000304). Meconium samples were collected from neonates of mothers with (n = 114) and without GDM (n = 133) within 24 h after birth, and then assessed via 16S rRNA gene amplicon sequencing. Differences in the diversity and composition of the neonatal gut microbiota were compared according to maternal GDM status and other perinatal characteristics. The gut microbiota of neonates born to mothers with GDM presented lower alpha diversity with the Chao1 index (P = 0.0235). Principal coordinate analysis revealed that the meconium samples were clustered by maternal GDM status only with unweighted UniFrac distances (R(2) = 0.011, P = 0.003). In other groups, such as maternal age ≥ 35 years old and maternal prepregnancy BMI ≥ 24 kg/m(2), meconium was not clustered by maternal GDM status. Linear discriminant analysis revealed that 81 taxa were significantly different between the GDM group and the control group. Based on delivery mode, there were 226 representative taxa in the control group, whereas in the GDM group, there were no representative taxa. In addition, based on neonatal sex, there were 79 representative taxa in the GDM group and seven in the control group. Other perinatal characteristics, such as maternal prepregnancy BMI, age, gestational weight gain, and birth weight also influenced the differential taxa of the neonatal gut microbiota between the two groups. In our cohort, newborns from mothers with GDM and without GDM had similar composition but different abundances of the gut microbiota. Maternal prepregnancy BMI, age, gestational weight gain, and neonatal delivery mode, sex, and birth weight had different influences on the diversity and differential taxa of the neonatal gut microbiota. The results of this study suggest that when studying the association between GDM and neonatal gut microbiota, it is necessary to consider the concomitant perinatal characteristics. IMPORTANCE: This study uses 16S rRNA gene amplicon sequencing to analyze 247 meconium samples with or without maternal gestational diabetes mellitus (GDM) and make a multi-group comparison. We found that newborns from mothers with GDM and normoglycemic mothers had similar compositions but different abundances of the gut microbiota. Other than the maternal diabetes status, maternal body mass index, age, gestational weight gain, and neonatal delivery mode, gender and birth weight all contribute to neonatal gut microbiota. Compared with former related studies, our sample size was larger, and meconium was collected within 24 h after birth to avoid the influence of the living environment, feeding methods, mother's lifestyle, or diet. The results of this study will provide some information on the association between maternal GDM and neonatal gut microbiota colonization in early life and highlight the influence of non-negligible concomitant perinatal characteristics.