Oral Presentation Australasian Diabetes in Pregnancy Society Annual Scientific Meeting 2024

Evolution of the microbiome from preconception to trimester 3 in the context of gestational diabetes mellitus (107419)

Lecquia N Chang 1 , Xin-Yi Chua 1 , Naomi Strout 1 , Michelle Fitzmaurice 1 , Emad El-Omar 1
  1. UNSW Microbiome Research Centre, Sydney, NSW, Australia

Background

Gestational diabetes mellitus (GDM) complicates 1 in 6 Australian births1. Although lifestyle modifications and medications are mainstay of GDM management, it cannot be prevented2. Understanding the preconception microbiome may assist in overcoming this shortcoming.

Aim of Research

To characterise the preconception and pregnancy microbiome of women who developed GDM compared with those who did not.

Methods

Our study was conducted as a substudy of the MothersBabies cohort, with pregnancy complications self-reported during virtual visits3. We collected maternal oral and stool samples at each trimester (T1, T2, T3) and used shotgun metagenomic sequencing to characterise the species profile from these samples at each timepoint, for both groups. Our rigorous approach included differential abundance analysis to filter species, and linear discriminant analysis to evaluate effect size, using microbiomeMarker (1.6.0) within R (v4.3.1) to pinpoint biomarkers (p <0.05 considered significant)4,5.

Results

Demographics: total women recruited (n=42); GDM cohort (n= 21, age, 33.19 years ± 3.97, BMI = 27.38 kg/m2 ± 5.55); and healthy controls (n=21, age, 32.81 years ± 3.89, BMI = 26.05 kg/m2 ± 5.33).

At preconception, GDM oral samples exhibited less enriched species compared to controls  (GDM = 2 species, controls = 17 species, p<0.05). Notably, Actinomyces sp000195595 was enriched (p<0.05) and Prevotella jejuni was reduced (p<0.05).

Oral species enrichment was not seen at T1, however, there were more enriched species in the GDM group at T2 (GDM = 14 species, controls = 6 species) and T3 (GDM = 24 species, controls = 20 species, p<0.05). Notably, enriched Phocaeicola vulgatus (T1), Porphyromonas somerae_A (T2) and Veillonella rogosae (T3) (p<0.05).

At preconception, the GDM group stool had higher levels of enriched species at preconception compared to control (GDM = 26 species, controls = 21 species)(p<0.05), including enriched Bacteroides eggerthi (p<0.05) but reduced Bacteroides cellulosilyticus (p<0.05).

GDM stool had less enriched species than controls at T1 (GDM = 14 species, controls = 43 species) and T2 (GDM = 11 species, controls = 35 species)(p<0.05), however, there was no difference at T3 (21 species in GDM and controls)(p<0.05). Remarkably, Phocaeicola dorei was reduced (p<0.05) and Bifidobacterium longum was enriched (p<0.05).

Conclusion  

We found enriched microorganisms in GDM mothers which are associated with inflammation, impaired glucose metabolism and SCFA production6-18. Additionally, our results suggest that the oral and stool maternal microbiome during preconception and pregnancy is distinguishable between women with and without GDM. Future functional analysis is warranted to determine the functional and causative role of the microbiome in GDM.

  1. Health, A.I.o. & Welfare. Diabetes: Australian facts. (AIHW, Canberra, 2023).
  2. Picon-Cesar, M.J., et al. Metformin for gestational diabetes study: metformin vs insulin in gestational diabetes: glycemic control and obstetrical and perinatal outcomes: randomised prospective trial. Am. J. Obstet. Gynecol. 225, 517 e511-517 e517 (2021).
  3. Strout, N., et al. The MothersBabies Study, an Australian Prospective Cohort Study Analysing the Microbiome in the Preconception and Perinatal Period to Determine Risk of Adverse Pregnancy, Postpartum, and Child-Related Health Outcomes: Study Protocol. Int. J. Environ. Res. Public Health. 20 (2023).
  4. Cao, Y., et al. microbiomeMarker: an R/Bioconductor package for microbiome marker identification and visualisation. Bioinform. 38, 4027-4029 (2022).
  5. Team, R.C. R: A language and environment for statistical computing. (R Foundation for Statistical Computing, Vienna, Austria, 2021).
  6. Widyarman, A.S., et al. Diversity of Oral Microbiome of Women From Urban and Rural Areas of Indonesia: A Pilot Study. Front. Oral Health. 2, 738306 (2021).
  7. Sun, X., et al. Alteration of salivary microbiome in periodontitis with or without type-2 diabetes mellitus and metformin treatment. Sci. Rep. 10, 15363 (2020).
  8. Ye, D., et al. Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans. Gut. Microbes. 15, 2154552 (2023).
  9. Liu, Y., et al. Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention. Cell. Metab. 31, 77-91 e75 (2020).
  10. Liu, S., et al. Oral microbial dysbiosis in patients with periodontitis and chronic obstructive pulmonary disease. Front. Cell. Infect. Microbiol. 13, 1121399 (2023).
  11. Camelo-Castillo, A.J., et al. Subgingival microbiota in health compared to periodontitis and the influence of smoking. Front. Microbiol. 6, 119 (2015).
  12. Guilloux, C.-A., Lamoureux, C., Beauruelle, C. & Héry-Arnaud, G. Porphyromonas: A neglected potential key genus in human microbiomes. Anaerobe 68, 102230 (2021).
  13. Mahmoudi, M., Kheder, R.K., Faraj, T.A., Abdulabbas, H.S. & Esmaeili, S.-A. Impacts of Porphyromonas gingivalis periodontitis on rheumatoid arthritis autoimmunity. Int. Immunopharmacol. 118, 109936 (2023).
  14. Lv, L.-J., et al. Deep metagenomic characterisation of gut microbial community and function in preeclampsia. Front. Cell. Infect. Microbiol. 12, 933523 (2022).
  15. Xiao, J.Z., et al. Effects of milk products fermented by Bifidobacterium longum on blood lipids in rats and healthy adult male volunteers. J. Dairy Sci. 86, 2452-2461 (2003).
  16. Shin, H.S., et al. Hypocholesterolemic effect of sonication-killed Bifidobacterium longum isolated from healthy adult Koreans in high cholesterol fed rats. Arch. Pharm. Res. 33, 14251431 (2010).
  17. Furse, S., Fernandez-Twinn, D.S., Chiarugi, D., Koulman, A. & Ozanne, S.E. Lipid metabolism is dysregulated before, during and after pregnancy in a mouse model of gestational diabetes. Int. J. Mol. Sci. 22, 7452 (2021).
  18. Liu, Y., et al. Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention. Cell. Metab. 31, 77-91 e75 (2020).