Diversified Microbiota of Meconium Is Affected by Maternal Diabetes Status

Jianzhong Hu,Holly Loudon,Joanne Stone,Steven Itzkowitz,Heriberto Fernandez-Hernandez,Zhiheng Pei,Yoko Nomura,Ali Bashir,Inga Peter,Herman Tse

doi:10.1371/journal.pone.0078257

Abstract

ObjectivesThis study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status.MethodsThe first intestinal discharge (meconium) was collected from 23 newborns stratified by maternal diabetes status: 4 mothers had pre-gestational type 2 diabetes mellitus (DM) including one mother with dizygotic twins, 5 developed gestational diabetes mellitus (GDM) and 13 had no diabetes. The meconium microbiome was profiled using multi-barcode 16S rRNA sequencing followed by taxonomic assignment and diversity analysis.ResultsAll meconium samples were not sterile and contained diversified microbiota. Compared with adult feces, the meconium showed a lower species diversity, higher sample-to-sample variation, and enrichment of Proteobacteria and reduction of Bacteroidetes. Among the meconium samples, the taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the DM group showing higher alpha-diversity than that of no-diabetes or GDM groups. No global difference was found between babies delivered vaginally versus via Cesarean-section. Regression analysis showed that the most robust predictor for the meconium microbiota composition was the maternal diabetes status that preceded pregnancy. Specifically, Bacteroidetes (phyla) and Parabacteriodes (genus) were enriched in the meconium in the DM group compared to the no-diabetes group.ConclusionsOur study provides evidence that meconium contains diversified microbiota and is not affected by the mode of delivery. It also suggests that the meconium microbiome of infants born to mothers with DM is enriched for the same bacterial taxa as those reported in the fecal microbiome of adult DM patients.

Highlights

Prenatal diabetes, which includes both pre-gestational Type 1 and Type 2 diabetes, and gestational diabetes that develops during pregnancy have been associated with an increased risk of obstetric and neonatal complications [1,2,3]
Five of the babies were born to mothers with established diabetes mellitus (DM), 5 to mothers with gestational diabetes mellitus (GDM), and 13 to mothers with subclinical diabetes (n = 4) or no diabetes (n = 9)
No significant difference was observed for TOS, BW and length among DM, GDM, and nodiabetes groups (p-value .0.1 by t-test)

Summary

Introduction

Prenatal diabetes, which includes both pre-gestational Type 1 and Type 2 diabetes, and gestational diabetes that develops during pregnancy have been associated with an increased risk of obstetric and neonatal complications [1,2,3]. Both pre-gestational and gestational diabetes have been associated with major birth defects [4] and congenital anomalies of the offspring [5,6]. Human microbiome studies have demonstrated dynamic changes in bacterial composition in the gut during pregnancy and childhood development [9,10,11]. Studies in mice have demonstrated the transmission of labeled bacterial strains from a mother to fetus during pregnancy [25]

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