Neonatal Med.  2023 Nov;30(4):89-95. 10.5385/nm.2023.30.4.89.

Clinical Applications of the Microbiome in Obstetrics

• Pyeon SY
• Kang DY
• Kim SY
• Choi SW
• Hwang MY
• Lee YJ

• KMID: 2548298
• DOI: http://doi.org/10.5385/nm.2023.30.4.89

Abstract

Human microbiome refers to the genetic material of approximately 10¹³ microorganisms present in the human body. These microbiomes interact significantly with the physiological, metabolic, and immune systems, particularly during pregnancy. Microbiome dysbiosis in pregnant women and their fetuses is associated with obstetric complications and poor neonatal outcomes. Oral and gut microbiomes can influence the placenta, uterus, and fetus via hematogenous translocation. Through ascending translocation, vaginal microbiota can directly affect the uterine environment. Current research focuses on the presence of the placental microbiome, which is characterized by low biomass. However, more well-controlled studies are required to specifically address the contamination issues. Use of antibiotics during pregnancy and the mode of delivery, specifically cesarean section, have been linked to the establishment of the neonatal gut microbiome. Probiotic supplementation may be beneficial during pregnancy, particularly for women receiving antibiotic treatment.

Keyword

Microbiota; Obstetrics; Complication; Placenta; Probiotics

Reference

1. O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006; 7:688–93.

2. Grice EA, Segre JA. The human microbiome: our second genome. Annu Rev Genomics Hum Genet. 2012; 13:151–70.

3. Walker RW, Clemente JC, Peter I, Loos RJF. The prenatal gut microbiome: are we colonized with bacteria in utero? Pediatr Obes. 2017; 12 Suppl 1:3–17.

4. Collado MC, Rautava S, Aakko J, Isolauri E, Salminen S. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep. 2016; 6:23129.

5. Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW, Nikita L, et al. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014; 2:4.

6. Campisciano G, Zanotta N, Licastro D, De Seta F, Comar M. In vivo microbiome and associated immune markers: new insights into the pathogenesis of vaginal dysbiosis. Sci Rep. 2018; 8:2307.

7. Balan P, Chong YS, Umashankar S, Swarup S, Loke WM, Lopez V, et al. Keystone species in pregnancy gingivitis: a snapshot of oral microbiome during pregnancy and postpartum period. Front Microbiol. 2018; 9:2360.

8. Daalderop LA, Wieland BV, Tomsin K, Reyes L, Kramer BW, Vanterpool SF, et al. Periodontal disease and pregnancy outcomes: overview of systematic reviews. JDR Clin Trans Res. 2018; 3:10–27.

9. Ye C, Katagiri S, Miyasaka N, Bharti P, Kobayashi H, Takeuchi Y, et al. The anti-phospholipid antibody-dependent and independent effects of periodontopathic bacteria on threatened preterm labor and preterm birth. Arch Gynecol Obstet. 2013; 288:65–72.

10. Parthiban PS, Mahendra J, Logaranjani A, Shanmugam S, Balakrishnan A, Junaid M, et al. Association between specific periodontal pathogens, Toll-like receptor-4, and nuclear factor-κB expression in placental tissues of pre-eclamptic women with periodontitis. J Investig Clin Dent. 2018; 9:e12265.

11. Wang J, Zheng J, Shi W, Du N, Xu X, Zhang Y, et al. Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus. Gut. 2018; 67:1614–25.

12. Cobb CM, Kelly PJ, Williams KB, Babbar S, Angolkar M, Derman RJ. The oral microbiome and adverse pregnancy outcomes. Int J Womens Health. 2017; 9:551–9.

13. Edwards SM, Cunningham SA, Dunlop AL, Corwin EJ. The maternal gut microbiome during pregnancy. MCN Am J Matern Child Nurs. 2017; 42:310–7.

14. Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K, Backhed HK, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012; 150:470–80.

15. Nuriel-Ohayon M, Neuman H, Ziv O, Belogolovski A, Barsheshet Y, Bloch N, et al. Progesterone increases Bifidobacterium relative abundance during late pregnancy. Cell Rep. 2019; 27:730–6.

16. Beghetti I, Barone M, Turroni S, Biagi E, Sansavini A, Brigidi P, et al. Early-life gut microbiota and neurodevelopment in preterm infants: any role for Bifidobacterium? Eur J Pediatr. 2022; 181:1773–7.

17. 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.

18. Pinto Y, Frishman S, Turjeman S, Eshel A, Nuriel-Ohayon M, Shrossel O, et al. Gestational diabetes is driven by microbiotainduced inflammation months before diagnosis. Gut. 2023; 72:918–28.

19. Chen X, Li P, Liu M, Zheng H, He Y, Chen MX, et al. Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation. Gut. 2020; 69:513–22.

20. Doyle RM, Harris K, Kamiza S, Harjunmaa U, Ashorn U, Nkhoma M, et al. Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes. PLoS One. 2017; 12:e0180167.

21. Dunlop AL, Mulle JG, Ferranti EP, Edwards S, Dunn AB, Corwin EJ. Maternal microbiome and pregnancy outcomes that impact infant health: a review. Adv Neonatal Care. 2015; 15:377–85.

22. Brown RG, Al-Memar M, Marchesi JR, Lee YS, Smith A, Chan D, et al. Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes. Transl Res. 2019; 207:30–43.

23. Tabatabaei N, Eren AM, Barreiro LB, Yotova V, Dumaine A, Allard C, et al. Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study. BJOG. 2019; 126:349–58.

24. Vitale SG, Ferrari F, Ciebiera M, Zgliczynska M, Rapisarda AM, Vecchio GM, et al. The role of genital tract microbiome in fertility: a systematic review. Int J Mol Sci. 2021; 23:180.

25. Aagaard K, Riehle K, Ma J, Segata N, Mistretta TA, Coarfa C, et al. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS One. 2012; 7:e36466.

26. Gudnadottir U, Debelius JW, Du J, Hugerth LW, Danielsson H, Schuppe-Koistinen I, et al. The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis. Sci Rep. 2022; 12:7926.

27. Chang DH, Shin J, Rhee MS, Park KR, Cho BK, Lee SK, et al. Vaginal microbiota profiles of native Korean women and associations with high-risk pregnancy. J Microbiol Biotechnol. 2020; 30:248–58.

28. Yan C, Hong F, Xin G, Duan S, Deng X, Xu Y. Alterations in the vaginal microbiota of patients with preterm premature rupture of membranes. Front Cell Infect Microbiol. 2022; 12:858732.

29. Dos Anjos Borges LG, Pastuschek J, Heimann Y, Dawczynski K; PEONS study group, Schleubner E, et al. Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis. BMC Med. 2023; 21:92.

30. Stout MJ, Conlon B, Landeau M, Lee I, Bower C, Zhao Q, et al. Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations. Am J Obstet Gynecol. 2013; 208:226.e1–7.

31. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014; 6:237. ra65.

32. Parnell LA, Briggs CM, Cao B, Delannoy-Bruno O, Schrieffer AE, Mysorekar IU. Microbial communities in placentas from term normal pregnancy exhibit spatially variable profiles. Sci Rep. 2017; 7:11200.

33. Panzer JJ, Romero R, Greenberg JM, Winters AD, Galaz J, Gomez-Lopez N, et al. Is there a placental microbiota?: a critical review and re-analysis of published placental microbiota datasets. BMC Microbiol. 2023; 23:76.

34. Selma-Royo M, Calvo Lerma J, Cortes-Macias E, Collado MC. Human milk microbiome: from actual knowledge to future perspective. Semin Perinatol. 2021; 45:151450.

35. Edwards CA, Van Loo-Bouwman CA, Van Diepen JA, Schoemaker MH, Ozanne SE, Venema K, et al. A systematic review of breast milk microbiota composition and the evidence for transfer to and colonisation of the infant gut. Benef Microbes. 2022; 13:365–81.

36. Azad MB, Konya T, Persaud RR, Guttman DS, Chari RS, Field CJ, et al. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG. 2016; 123:983–93.

37. Kim S, Oh JW, Yun JW. Narrative review on the trend of childbirth in South Korea and feasible intervention to reduce cesarean section rate. J Korean Soc Matern Child Health. 2023; 27:1–13.

38. Liu Y, Qin S, Song Y, Feng Y, Lv N, Xue Y, et al. The perturbation of infant gut microbiota caused by cesarean delivery is partially restored by exclusive breastfeeding. Front Microbiol. 2019; 10:598.

39. Mueller NT, Dominguez-Bello MG, Appel LJ, Hourigan SK. ‘Vaginal seeding’ after a caesarean section provides benefits to newborn children: FOR: does exposing caesarean-delivered newborns to the vaginal microbiome affect their chronic disease risk?: the critical need for trials of ‘vaginal seeding’ during caesarean section. BJOG. 2020; 127:301.

40. Butler EM, Chiavaroli V, Derraik JG, Grigg CP, Wilson BC, Walker N, et al. Maternal bacteria to correct abnormal gut microbiota in babies born by C-section. Medicine (Baltimore). 2020; 99:e21315.

41. Limaye MA, Ratner AJ. ‘Vaginal seeding’ after a caesarean section provides benefits to newborn children: AGAINST: vaginal microbiome transfer: a medical procedure with clear risks and uncertain benefits. BJOG. 2020; 127:302.

42. Wilson BC, Butler EM, Grigg CP, Derraik JG, Chiavaroli V, Walker N, et al. Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: a pilot randomised placebo-controlled trial. EBioMedicine. 2021; 69:103443.

43. Navarro-Tapia E, Sebastiani G, Sailer S, Toledano LA, Serra-Delgado M, Garcia-Algar O, et al. Probiotic supplementation during the perinatal and infant period: effects on gut dysbiosis and disease. Nutrients. 2020; 12:2243.

44. Martin-Pelaez S, Cano-Ibanez N, Pinto-Gallardo M, Amezcua-Prieto C. The impact of probiotics, prebiotics, and synbiotics during pregnancy or lactation on the intestinal microbiota of children born by cesarean section: a systematic review. Nutrients. 2022; 14:341.

45. Homayouni A, Bagheri N, Mohammad-Alizadeh-Charandabi S, Kashani N, Mobaraki-Asl N, Mirghafurvand M, et al. Prevention of gestational diabetes mellitus (GDM) and probiotics: mechanism of action: a review. Curr Diabetes Rev. 2020; 16:538–45.

46. Taylor BL, Woodfall GE, Sheedy KE, O’Riley ML, Rainbow KA, Bramwell EL, et al. Effect of probiotics on metabolic outcomes in pregnant women with gestational diabetes: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2017; 9:461.

47. Movaghar R, Farshbaf-Khalili A, Hajizade K, MirzaRezaei ME, Shahnazi M. The effect of probiotics or synbiotics on the hypertensive disorders of pregnant women with gestational diabetes: a systematic review and meta-analysis. J Caring Sci. 2022; 11:94–104.

48. Mahdizade Ari M, Teymouri S, Fazlalian T, Asadollahi P, Afifirad R, Sabaghan M, et al. The effect of probiotics on gestational diabetes and its complications in pregnant mother and newborn: a systematic review and meta-analysis during 2010-2020. J Clin Lab Anal. 2022; 36:e24326.

49. Davidson SJ, Barrett HL, Price SA, Callaway LK, Dekker Nitert M. Probiotics for preventing gestational diabetes. Cochrane Database Syst Rev. 2021; 4:CD009951.

50. Yang S, Reid G, Challis JR, Kim SO, Gloor GB, Bocking AD. Is there a role for probiotics in the prevention of preterm birth? Front Immunol. 2015; 6:62.

51. Jarde A, Lewis-Mikhael AM, Moayyedi P, Stearns JC, Collins SM, Beyene J, et al. Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2018; 18:14.

52. Elias J, Bozzo P, Einarson A. Are probiotics safe for use during pregnancy and lactation? Can Fam Physician. 2011; 57:299–301.