Gestational diabetes-related gut microbiome dysbiosis is not influenced by different Asian ethnicities and dietary interventions: a pilot study

Abstract

Gut microbiome dysbiosis contributes to the pathophysiology of both gestational diabetes mellitus (GDM) and its associated adverse outcomes in the woman and offspring. Even though GDM prevalence, complications, and outcomes vary among different ethnic groups, limited information is available about the influence of ethnicity on gut microbiome dysbiosis in pregnancies complicated by GDM. This pilot prospective cohort study examined the impact of ethnicity on gut dysbiosis in GDM among three Asian ethnic groups (Chinese, Malay, Indian) living in Singapore, and investigated the potential modulatory roles of diet and lifestyle modifications on gut microbiome post-GDM diagnosis. Women with GDM (n = 53) and without GDM (n = 16) were recruited. Fecal samples were collected at 24-28- and 36-40-weeks' gestation and analyzed by targeted 16S rRNA gene-based amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) analysis was performed to evaluate differences between groups. Differentially abundant taxa were identified by DeSeq2 based analysis. Functional prediction was performed using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). Among women with GDM, gut microbiome from different ethnicities harbored common microbial features. However, among those without GDM, there was contrasting microbiome composition between ethnic groups. Microbial members such as Collinsella, Blautia, Ruminococcus, Ruminococcus gnavus, Ruminococcus torques, and Eubacterium hallii groups were differentially enriched (p < 0.05) in women with GDM compared to those without. Among women with GDM, no differences in alpha- and beta- diversity were observed when comparing 24-28 weeks' samples with 36-40 weeks' samples, a period covering intense dietary and lifestyle modification, suggesting an inability to modulate gut microbiota through classic GDM management. Women with GDM have a distinct gut microbiome profile which harbours common features across different Asian ethnic groups, consistent with the notion that specific microbes are involved in the pathogenesis of insulin resistance, pro-inflammatory conditions, and other metabolic dysregulation known to be present in GDM.

Figure 1

Microbiome composition of women with and without GDM. (a) α-diversity metrics of the gut microbiome; (b) PCoA-based analysis of the gut microbiome. *p < 0.05; **p < 0.01; ***p < 0.001; ns-non-significant.

Figure 2

Change in bacterial composition between women with and without GDM across the three ethnic groups. (a) bacterial composition at phylum level in women with and without GDM; (b) bacterial composition at phylum level in the different ethnic groups. * p < 0.05; ** p < 0.01; *** p < 0.001; ns-non-significant.

Figure 3

Heatmap based hierarchical clustering based on Bray Curtis dissimilarity matrix and Wald test of bacterial taxa and other parameters. Red dots represent the taxa which are significantly (Wilcoxon test, p < 0.05) abundant in women with GDM, while green dots represent the taxa significantly (Wilcoxon test, p < 0.05) abundant in women without GDM. The heatmap was generated using pheatmap package v1.0.12 .

Figure 4

Volcano plot represent the differentially abundant ASVs (p. adjusted < 0.001) identified from DeSeq2-based analysis between women with and without GDM.

Figure 5

Microbial composition of women with GDM at two time points. (a) α-diversity metrics of the gut microbiome; (b) PCoA-based analysis of the gut microbiome between the two time points of women with GDM; (c) Bacterial composition of major phyla. * p < 0.05; ** p < 0.01; ***p < 0.001; ns-non-significant.

Figure 6

Microbial composition of women with at two time points based on ethnicity groupings. (a) α-diversity metrics of the gut microbiome; (b) PCoA-based analysis of the gut microbiome; (c) Bacterial composition of major genera. *p < 0.05; **p < 0.01; ***p < 0.001; ns-non-significant.

Figure 7

Changes in microbiome composition of women with GDM upon dietary interventions. (a) PCoA-based analysis of the gut microbiome of women with GDM after dietary interventions; (b) Heatmap-based Spearman correlation association between dietary intake and bacterial genera at 36–40 weeks of gestation. *p < 0.05; **p < 0.01; ***p < 0.001; ns-non-significant. Spearman correlation based heatmap was generated using corrplot package v0.92.