Ms Sophie Leech1, Dr Emily Dorey2, Dr Thomas Mullins2, A/Prof Helen Barrett3,4, A/Prof. Marloes Dekker Nitert1
1School of Chemistry and Molecular Biosciences,The University Of Queensland, St Lucia, Australia, 2Mater Research Institute – The University of Queensland, South Brisbane, Australia, 3Obstetric Medicine, Royal Hospital for Women, Randwick, Australia, 4Faculty of Medicine, The University of New South Wales, Sydney, Australia
Biography:
A/Prof Marloes Dekker Nitert is a teaching and research academic at the School of Chemistry and Molecular Biosciences at the University of Queensland. She leads a research group focused on understanding how the gut microbiome contributes to health and disease in pregnancy.
Abstract:
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 compare the composition and functionality of the gut microbiome of pregnant women with and without 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-BC2’ and ‘Maaslin2’.
Results: The gut microbiota in women with T2DM had lower alpha diversity (decreased Shannon index (p=0.006); evenness (p=0.02) and richness (p=0.02)). Beta diversity was also significantly different (R2=0.04, p=0.02). At the taxonomy level, depletions in Dysosmobacter BX15 (q=0.008) and unidentified Firmicutes species GGB9758 SGB15368 were identified in women with T2DM. Another species of the same genus Dysosmobacter welbionis reportedly prevents diet-induced obesity and insulin resistance in mice (1) and increased with metformin use in people with obesity and diabetes (2). Several functional pathways were differentially abundant in women with T2DM including enrichment of PWY-8190, which produces the SCFA acetate and butanoate from L-glutamate in a reductive Stickland reaction (Maaslin2: q=0.002).
Conclusion: The gut microbiome of women with pre-existing T2DM in pregnancy significantly differs from normoglycaemic women with changes in taxonomic and functional profiles. As a next step, we will assess the SCFA concentration in serum and stool.
Keywords
Gut microbiome, type 2 diabetes, pregnancy
References
1. Le Roy T, Moens de Hase E, Van Hul M, Paquot A, Pelicaen R, Régnier M, et al. <em>Dysosmobacter welbionis</em> is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice. Gut. 2022;71(3):534.
2. Moens de Hase E, Neyrinck AM, Rodriguez J, Cnop M, Paquot N, Thissen J-P, et al. Impact of metformin and Dysosmobacter welbionis on diet-induced obesity and diabetes: from clinical observation to preclinical intervention. Diabetologia. 2024;67(2):333-45.