Introduction: Outside pregnancy the gut microbiome is thought to play a role in the pathogenesis of Type 2 diabetes mellitus (T2DM) with depletions in short-chain fatty acid (SCFA) producing bacteria and increases in intestinal permeability and inflammation. However, in pregnancy, only one study examining the relationship between pre-existing T2DM and the gut microbiome exists. As pregnancy is a time of significant hormonal and metabolic change, we aimed to examine the composition and functionality of the gut microbiome of pregnant women with pre-existing T2DM.
Methods: Stool from 9 women with pre-existing Type 2 diabetes mellitus and 26 normoglycaemic controls between 24- and 31-weeks’ gestation was collected. The profile of the gut microbiome was assessed from shotgun metagenomic sequence data. Community composition was assessed using MetaPhlAn 4.0.6 and functional analysis was conducted with HUMAnN 3.6. Analysis was conducted with GraphPad Prism 9.0.2. and RStudio packages ‘phyloseq’, ‘MixOmics’, ‘vegan’, ‘ANCOM-BC’ and ‘Maaslin2’.
Results: T2DM women had lower Shannon indices (p = 0.0058) with decreased evenness (p = 0.0228) and richness (p = 0.0155) of the gut microbiota. Beta diversity was also significantly different (R2 = 0.043, p = 0.018). No significant differences were detected using Maaslin2 at any taxonomy level after correction for multiple comparisons. However, ANCOM-BC identified multiple differentially abundant taxa such as depletions in Candidatus Avimonas narfia SGB14941 (q = 0.045) in T2DM women. Several functional pathways were differentially abundant including PWY-8190 which produces SCFA acetate and butanoate and was enriched in T2DM (Maaslin2: q = 0.0017, ANCOM-BC: q = 0.0012) and PWY-5747 (ANCOM-BC: q = 0.036), which describes the degradation of SCFA propionate.
Conclusion: The gut microbiome of women with pre-existing T2DM in pregnancy significantly differs from normoglycaemic women with changes in two SCFA pathways. As a next step, we will assess the SCFA concentration in serum and stool.