Diversified gut microbiota in newborns of mothers with gestational diabetes mellitus

Abstract

Gestational diabetes mellitus (GDM), a high-risk pregnancy complication of great effect on the perinatal health of women and newborns, may cause changes of gut microbiota in mothers and further affect gut microbiota in newborns. This study aimed to investigate the potential effect of mother GDM on newborns' gut microbiota. Meconium DNA was extracted from a total of 34 full-term and C-sectioned newborns, in which 20 newborns had mothers diagnosed with GDM, while 14 had unaffected mothers. Sequencing and bioinformatics analysis of 16S rRNA indicated that the gut microbiota of GDM newborns showed differences compared to control newborns. The taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the GDM group showing lower alpha-diversity than that of control group. The phyla of Proteobacteria and Actinobacteria in GDM newborns increased, while that of Bacteroidetes significantly reduced (P<0.05). Moreover, several unique gut microbiota in phylum of Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Chloroflexi, Acidobacteria, and Planctomycetes found in control newborns were absent in GDM ones. At genus level, the relative abundance of Prevotella and Lactobacillus significantly decreased (P<0.05) in GDM newborns. Correlation analysis indicated that maternal fasting glucose levels were positively correlated with the relative abundance of phylum Actinobacteria and genus Acinetobacter, while negatively correlated with that of phylum Bacteroidetes and genus Prevotella. However, bacteria in GDM grade A2 (GDM_A2) newborns did not show any statistical variation compared to those from control newborns, which might be attributed to the additional intervention by insulin. The results of this study have important implications for understanding the potential effects of GDM on the gut microbiota of newborns and thus possibly their metabolism at later stages in their lives.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Altered biodiversity of gut microbiota in the GDM groups in comparison with control group.

The groups of control (n=14), GDM_A1 (n=15), GDM_A2 (n=5) and GDM_Total (n=A1+A2=20) were described in the Methods. (A, B) The ecological diversity of gut microbiota in the control and GDM groups was measured by Shannon index and Simpson index. (C, D) The alpha-diversity, richness of gut microbiota, was determined by Chao1 index and Observed species index.

Fig 2. The beta-diversity of the microbial communities in the control and GDM groups.

(A) Principal Coordinates Analysis (PCoA) plot based on weighted UniFrac distance. Each dot represents one sample from each group. (B) Beta-diversity index difference based on weighted UniFrac. The P-values were calculated using Wilcoxon test. Statistical significance is displayed as * P < 0.05 and ** P < 0.01.

Fig 3. The major gut bacterial phyla and genus in the control and GDM groups.

(A) Bacterial phylum levels of each sample in the groups of control, GDM_A1 and GDM_A2 respectively. (B) Bacterial phylum average levels of each group. (C) Bacterial genus levels of each sample in the groups of control, GDM_A1 and GDM_A2 respectively. (D) Bacterial genus average levels of each group.

Fig 4. Comparison of gut microbiota of relative abundance at the bacterial phylum levels between GDM groups and control group.

The P-values were calculated using Mann-Whitney test, and significance was compared against the control group. *P < 0.05. **P < 0.01.

Fig 5. Comparison of gut microbiota of relative abundance at the bacterial genus levels between GDM groups and control group.

The P-values were calculated using Mann-Whitney test, and significance was compared against the control group. *P < 0.05.

Fig 6. Comparison of the amount of unique gut microbiota at different bacterial taxonomic levels between GDM and control group in the main phyla.

(A) Phylum level. (B) Genus level.

Fig 7. Correlations between maternal fasting glucose and gut microbiota in meconium samples of newborns.

Spearman’s rank correlation coefficients and P-values for the correlations are shown. (A) Positive correlation between maternal fasting glucose and phylum Actinobacteria (ρ=0.445, P=0.011). (B) Negative correlation between maternal fasting glucose and phylum Bacteroidetes (ρ=-0.414, P=0.018). (C) Positive correlation between maternal fasting glucose and genus Acinetobacter (ρ=0.406, P=0.021). (D) Negative correlation between maternal fasting glucose and genus Prevotella (ρ=-0.393, P=0.026).