Diversified microbiota of meconium is affected by maternal diabetes status

Abstract

Objectives: This study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status.

Methods: The 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.

Results: All 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.

Conclusions: Our 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.

Figure 1. Comparison of the microbiota communities of neonate meconium to adult stool samples.

A. Classification of the microbiota at the Phylum level. Samples BM62-BM140 are neonate meconium and 7 samples are from healthy adults. The total reads for each sample are normalized to 2000. Neonate meconium samples are grouped by maternal clinical status: Healthy, subclinical, GDM (gestational diabetes) and DM (type 2 diabetes). B. Average taxa abundances between the neonate meconium and adult stool samples. HC group combined healthy and subclinical samples. C. Alpha rare plot shows the average microbiota diversity of the neonate meconium grouped by maternal status (HC, GDM and DM) and adult stool samples.

Figure 2. Comparison of the OTUs at the Phylum and Family level between healthy adult stool samples and the meconium samples from neonates born to mothers with no diabetes.

The meconium samples included both HC and subclinical groups. Only OTUs shown significance (p values <0.05 by WMW-test and adjusted by BH method) between the two groups are presented.

Figure 3. Comparison of meconium microbiota from neonates born to HC (healthy), DM (type 2 diabetes) and GDM (gestational diabetes) mothers using nMDS ordination.

The unweighted UniFrac distance matrices generated from QIIME were visualized in nMDS plot. Lines connect individual communities to the centroid values for each group. The ellipses were drawn to represent the class standard errors.

Figure 4. List of OTUs that showed significant difference between neonates from mothers with different diabetes states.

HC(healthy) group was combined with both healthy and subclinical groups. *unadjusted p-value from WMW-test between HC and DM(type 2 diabetes) group; **unadjusted p-value from WMW-test between HC and GDM(gestational diabetes) group.