Microbiome alterations in women with gestational diabetes mellitus (literature review)

Background. Gestational Diabetes Mellitus (GDM) is a common disorder that is getting a special attention recently due to the unwanted outcomes that it leaves on the health of both the women and their offspring. New approaches are being applied in order to develop strategies that prevent GDM and its consequences on the metabolic and physiological state. One of the factors that have been thought to be involved in the pathology behind this disorder is the microbiome.

Objective: to determine the current evidence regarding the association of the maternal microbiota composition with gestational diabetes mellitus and to discuss the possibility of the management of GDM using the microbiome.

Material and methods. An extensive literature review was conducted using the MEDLINE database (PubMed) using keywords and filter: randomized controlled trial, meta-analysis, systematic review.

Research results. This review summarizes the main data on the influence of microbiota composition and diversity on the occurrence and development of GDM. Although there were some inconsistencies among the results, a pattern of significant changes in the gut, oral, and vaginal microbiome of women with GDM was observed. It was found that the composition and diversity of gut microbiota were significantly associated with the occurrence and development of GDM. Specifically, the abundance of certain gut bacteria is associated with anincreased risk of GDM, while other changes in the microbiome may beassociated with improved insulin sensitivity. In addition, alterations in the gutmicrobiota may affect blood glucose control through a variety of mechanisms, including the production of short-chain fatty acids, activation of inflammatory pathways, and metabolism of the B vitamin group.

Conclusion. We concluded a clear existing correlation between GDM and the microbial communities, where specific patterns of alterations in the microbiome was observed in the gut, oral and vaginal tracts of the pregnant women. These findings, although having some limitations, are promising and encouraging to develop strategies that target the human microbiome in order to develop novel therapeutic plans to treat or prevent GDM using next generation probiotics and parabiotics. Future studies should assess the outcomes and the efficacy of such therapeutic methods.

1. Hasain Z., Mokhtar N.M., Kamaruddin N.A., et al. Gut Microbiota and Gestational Diabetes Mellitus: A Review of Host-Gut Microbiota Interactions and Their Therapeutic Potential. Front Cell Infect Microbiol. 2020; 10:188. DOI: https://doi.org/10.3389/fcimb.2020.00188

2. Wang H., Li N., Chivese T., et al. IDF Diabetes Atlas: Estimation of Global and Regional Gestational Diabetes Mellitus Prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group’s Criteria. Diabetes Res Clin Pract. 2022; 183:109050. DOI: https://doi.org/10.1016/j.diabres.2021.109050

3. Clinical guidelines Gestational diabetes mellitus. Project. 2024. (In Russ). https://raeorg.ru/system/files/documents/pdf/cr_gmd_24.pdf

4. Burumkulova F.F., Petrukhin V.A. Gestational diabetes mellitus: yesterday, today, tomorrow: review. Therapeutic Archive. 2014; 86(10): 109-115. (In Russ).

5. Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med. 2008; 358(19): 1991-2002. DOI: https://doi.org/10.1056/nejmoa0707943

6. Chaplin A.V., Rebrikov D.V., Boldyreva M.N. The human microbiome. Bull Russ State Med Univ. 2017; (2):5-13. (In Russ).

7. Zinina T.A., Tiselko A.V., Yarmolinskaya M.I. The role of intestinal microbiota in the development of complications in pregnant women with gestational diabetes. J Obstet Womens Dis. 2020; 69(4): 41-50. (In Russ).

8. Yao Y., Cai X., Chen C., et al. The Role of Microbiomes in Pregnant Women and Offspring: Research Progress of Recent Years. Front Pharmacol. 2020; 11:643. DOI: https://doi.org/10.3389/fphar.2020.00643

9. Saad M.J., Santos A., Prada P.O. Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance. Physiology. 2016; 31(4): 283-293. DOI: https://doi. org/10.1152/physiol.00041.2015

10. Taddei C.R., Cortez R.V., Mattar R., Torloni M.R., Daher S. Microbiome in normal and pathological pregnancies: A literature overview. Am J Reprod Immunol. 2018; 80(2):e12993. DOI: https://doi.org/10.1111/aji.12993

11. Onopriychuk A.R., Kapustin R.V., Arzhanova O.N. The role of gut microbiota in the development of gestational diabetes mellitus. Akush Ginekol (Sofiia). 2020; 3_2020:18-24. (In Russ).

12. Moumne O., Hampe M.E., Montoya-Williams D., et al. Implications of the vaginal microbiome and potential restorative strategies on maternal health: a narrative review. J Perinat Med. 2021; 49(4):402-411. DOI: https://doi.org/10.1515/jpm-2020-0367

13. Jang H., Patoine A., Wu T.T., Castillo D.A., Xiao J. Oral microflora and pregnancy: a systematic review and meta-analysis. Sci Rep. 2021; 11(1):16870. DOI: https://doi.org/10.1038/s41598-021-96495-1

14. Dabke K., Hendrick G., Devkota S. The gut microbiome and metabolic syndrome. J Clin Invest. 2019; 129(10):4050- 4057. DOI: https://doi.org/10.1172/jci129194

15. Chen X., Devaraj S. Gut Microbiome in Obesity, Metabolic Syndrome, and Diabetes. Curr Diab Rep. 2018; 18(12):129. DOI: https://doi.org/10.1007/s11892-018-1104-3

16. Qin J., Li Y., Cai Z., et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012; 490(7418):55-60. DOI: https://doi.org/10.1038/nature11450

17. Kunasegaran T., Balasubramaniam V.R., Arasoo V.J., Palanisamy U.D., Ramadas A. The Modulation of Gut Microbiota Composition in the Pathophysiology ofGestational Diabetes Mellitus: A Systematic Review. Biology. 2021;10(10):1027. DOI: https://doi.org/10.3390/biology10101027

18. Neuman H., Koren O. The Pregnancy Microbiome. In: Isolauri E, Sherman PM, Walker WA, eds. Nestlé Nutrition Institute Workshop Series. Vol 88. S. Karger AG; 2017:1-10. DOI: https://doi.org/10.1159/000455207

19. Ma S., Wang Y., Ji X., et al. Relationship between gut microbiota and the pathogenesis of gestational diabetes mellitus: a systematic review. Front Cell Infect Microbiol. 2024; 14:1364545. DOI: https://doi.org/10.3389/fcimb.2024.1364545

20. Farhat S., Hemmatabadi M., Ejtahed H.S., Shirzad N., Larijani B. Microbiome alterations in women with gestational diabetes mellitus and their offspring: A systematic review. Front Endocrinol. 2022; 13:1060488. DOI: https://doi.org/10.3389/fendo.2022.1060488

21. De Siena M., Laterza L., Matteo M.V., et al. Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy. Microorganisms. 2021; 9(3):473. DOI: https://doi.org/10.3390/microorganisms9030473

22. Yudina Y.V., Korsunsky A.A., Aminova A.I., Abdullaeva G.D., Prodeus A.P. Gut microbiota as a separate body system. Dokazatelnaya Gastroenterol. 2019;8 (4-5):36. (In Russ).

23. Egshatyan L., Kashtanova D., Popenko A., et al. Gut microbiota and diet in patients with different glucose tolerance. Endocr Connect. 2016;5(1):1-9. DOI: https://doi.org/10.1530/ec-15-0094

24. Le Chatelier E., Nielsen T., Qin J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013; 500(7464):541-546. DOI: https://doi.org/10.1038/nature12506

25. Rivière A., Selak M., Lantin D., Leroy F., De Vuyst L. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut. Front Microbiol. 2016; 7. DOI: https://doi.org/10.3389/fmicb.2016.00979

26. Ottosson F., Brunkwall L., Ericson U., et al. Connection Between BMI-Related Plasma Metabolite Profile and Gut Microbiota. J Clin Endocrinol Metab. 2018; 103(4):1491- 1501. DOI: https://doi.org/10.1210/jc.2017-02114

27. Fugmann M., Breier M., Rottenkolber M., et al. The stool microbiota of insulin resistant women with recent gestational diabetes, a high risk group for type 2 diabetes. Sci Rep. 2015; 5(1):13212. DOI: https://doi.org/10.1038/srep13212

28. Koren O., Goodrich J.K., Cullender T.C., et al. Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy. Cell. 2012; 150(3):470-480. DOI: https://doi.org/10.1016/j.cell.2012.07.008

29. Cobb C., Kelly P., Williams K., Babbar S., Angolkar M., Derman R. The oral microbiome and adverse pregnancy outcomes. Int J Womens Health. 2017; Volume 9:551-559. DOI: https://doi.org/10.2147/ijwh.s142730

30. Zarco M., Vess T., Ginsburg G. The oral microbiome in health and disease and the potential impact on personalized dental medicine. Oral Dis. 2012; 18(2):109-120. DOI: https://doi.org/10.1111/j.1601-0825.2011.01851.x

31. Gao L., Xu T., Huang G., Jiang S., Gu Y., Chen F. Oral microbiomes: more and more importance in oral cavity and whole body. Protein Cell. 2018; 9(5):488-500. DOI: https://doi.org/10.1007/s13238-018-0548-1

32. He Z., Wu J., Xiao B., Xiao S., Li H., Wu K. The Initial Oral Microbiota of Neonates Among Subjects With Gestational Diabetes Mellitus. Front Pediatr. 2019;7:513. DOI: https://doi.org/10.3389/fped.2019.00513

33. Shipitsyna EV. Placental Microbiome: a Paradigm Shift or Flaw in the Methodology? Ann Russ Acad Med Sci. 2021; 76(5):436-448. (In Russ).

34. Bassols J., Serino M., Carreras-Badosa G., et al. Gestational diabetes is associated with changes in placental microbiota and microbiome. Pediatr Res. 2016; 80(6):777-784. DOI: https://doi.org/10.1038/pr.2016.155

35. Tang N., Luo Z.C., Zhang L., et al. The Association Between Gestational Diabetes and Microbiota in Placenta and Cord Blood. Front Endocrinol. 2020; 11:550319. DOI: https://doi.org/10.3389/fendo.2020.550319

36. Stinson L.F., Payne M.S., Keelan J.A. Planting the seed: Origins, composition, and postnatal health significance of the fetal gastrointestinal microbiota. Crit Rev Microbiol. 2017; 43(3):352-369. DOI: https://doi.org/10.1080/1040841x.2016.1211088

37. Olomu I.N., Pena-Cortes L.C., Long R.A., et al. Elimination of “kitome” and “splashome” contamination results in lack of detection of a unique placental microbiome. BMC Microbiol. 2020; 20(1):157. DOI: https://doi.org/10.1186/s12866-020-01839-y

38. Palleja A., Mikkelsen K.H., Forslund S.K., et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat Microbiol. 2018; 3(11):1255-1265. DOI: https://doi.org/10.1038/s41564-018-0257-9

39. Medici Dualib P., Ogassavara J., Mattar R., Mariko Koga Da Silva E., Atala Dib S, De Almeida Pititto B. Gut microbiota and gestational Diabetes Mellitus: A systematic review. Diabetes Res Clin Pract. 2021; 180:109078. DOI: https://doi.org/10.1016/j.diabres.2021.109078

40. Rold L.S., Bundgaard-Nielsen C., Niemann HolmJacobsen J., et al. Characteristics of the gut microbiome in women with gestational diabetes mellitus: A systematic review. Chong CW, ed. PLOS ONE. 2022; 17(1):e0262618. DOI: https://doi.org/10.1371/journal.pone.0262618

41. Han M.M., Sun J.F., Su X.H., et al. Probiotics improve glucose and lipid metabolism in pregnant women: a meta-analysis. Ann Transl Med. 2019; 7(5):99-99. DOI: https://doi.org/10.21037/atm.2019.01.61.