Probiotics in the Prevention of Gestational Diabetes Mellitus (GDM)

  • Luisa F. Gomez Arango
  • Helen L. Barrett
  • Leonie K. Callaway
  • H. David McIntyre
  • Marloes Dekker NitertEmail author
Part of the Nutrition and Health book series (NH)


The microbiome, the composite of bacteria present on the human body, has a critical role in the regulation of metabolism, immune function, and behavior. In pregnancy, the gut microbiota is altered, becoming less diverse as pregnancy progresses. The oral, vaginal, and placental microbiotas may also be affected by pregnancy. These changes may contribute to maternal physiological changes in pregnancy. Outside pregnancy, obesity, and diabetes are associated with changes to the composition of the gut microbiota. Whether or not obesity and diabetes compound pregnancy-associated changes to the microbiome is unclear. Manipulation of the gut microbiota by probiotic supplementation may be a strategy to prevent the development of gestational diabetes mellitus. In this chapter, the pregnancy-associated changes to the microbiome and the effects of probiotic supplementation on the prevention of gestational diabetes mellitus will be discussed.


Gestational diabetes mellitus Microbiome Metabolism Pregnancy Probiotics Prebiotics Pregnancy complications 



Gestational diabetes mellitus


Homeostatic model assessment of beta cell function


Homeostatic model assessment of insulin resistance


High sensitivity C-reactive protein


Short chain fatty acids


Very low-density lipoprotein


  1. 1.
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. bioRxiv. 2016.Google Scholar
  3. 3.
    Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859–904.CrossRefPubMedGoogle Scholar
  5. 5.
    Fujimura KE, Slusher NA, Cabana MD, Lynch SV. Role of the gut microbiota in defining human health. Expert Review of Anti-infective Therapy. 2010;8(4):435–54.Google Scholar
  6. 6.
    Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y, Li H, et al. The maternal microbiota drives early postnatal innate immune development. Science. 2016;351(6279):1296–302.CrossRefPubMedGoogle Scholar
  7. 7.
    Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008;88(4):894–9.PubMedGoogle Scholar
  8. 8.
    Koren O, Goodrich Julia K, Cullender Tyler C, Spor A, Laitinen K, Kling Bäckhed H, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150(3):470–80.Google Scholar
  9. 9.
    Jost T, Lacroix C, Braegger C, Chassard C. Stability of the maternal gut microbiota during late pregnancy and early lactation. Curr Microbiol. 2014;68(4):419–27.CrossRefPubMedGoogle Scholar
  10. 10.
    Mukhopadhya I, Hansen R, El-Omar EM, Hold GL. IBD-what role do Proteobacteria play? Nat Rev Gastroenterol Hepatol. 2012;9(4):219–30.CrossRefPubMedGoogle Scholar
  11. 11.
    Avershina E, Storrø O, Øien T, Johnsen R, Pope P, Rudi K. Major faecal microbiota shifts in composition and diversity with age in a geographically restricted cohort of mothers and their children. FEMS Microbiol Ecol. 2014;87(1):280–90.CrossRefPubMedGoogle Scholar
  12. 12.
    Gohir W, Ratcliffe EM, Sloboda DM. Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk. Pediatr Res. 2015;77(1–2):196–204.CrossRefPubMedGoogle Scholar
  13. 13.
    Santacruz A, Collado MC, Garcia-Valdes L, Segura MT, Martin-Lagos JA, Anjos T, et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr. 2010;104(1):83–92.Google Scholar
  14. 14.
    Nadal I, Santacruz A, Marcos A, Warnberg J, Garagorri JM, Moreno LA, et al. Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obes (Lond). 2009;33(7):758–67.CrossRefGoogle Scholar
  15. 15.
    Priyadarshini M, Thomas A, Reisetter AC, Scholtens DM, Wolever TM, Josefson JL, et al. Maternal short-chain fatty acids are associated with metabolic parameters in mothers and newborns. Transl Res. 2014;164(2):153–7.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Voltolini C, Battersby S, Etherington SL, Petraglia F, Norman JE, Jabbour HN. A novel antiinflammatory role for the short-chain fatty acids in human labor. Endocrinology. 2012;153(1):395–403.CrossRefPubMedGoogle Scholar
  17. 17.
    Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE. 2010;5(2):e9085.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913–6.e7.Google Scholar
  19. 19.
    Fugmann M, Breier M, Rottenkolber M, Banning F, Ferrari U, Sacco V, et al. The stool microbiota of insulin resistant women with recent gestational diabetes, a high risk group for type 2 diabetes. Sci Rep. 2015;5:13212.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Aagaard K, Riehle K, Ma J, Segata N, Mistretta T-A, Coarfa C, et al. A Metagenomic Approach to Characterization of the Vaginal Microbiome Signature in Pregnancy. PLoS ONE. 2012;7(6):e36466.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    DiGiulio DB, Callahan BJ, McMurdie PJ, Costello EK, Lyell DJ, Robaczewska A, et al. Temporal and spatial variation of the human microbiota during pregnancy. 2015;112(35):11060–5.Google Scholar
  22. 22.
    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(1):4.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C, Husslein P. Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol. 2003;189(1):139–47.CrossRefPubMedGoogle Scholar
  24. 24.
    Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, et al. The human oral microbiome. J Bacteriol. 2010;192(19):5002–17.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Wade WG. The oral microbiome in health and disease. Pharmacol Res. 2013;69(1):137–43.CrossRefPubMedGoogle Scholar
  26. 26.
    Solt I. The human microbiome and the great obstetrical syndromes: a new frontier in maternal-fetal medicine. Best Pract Res Clin Obstet Gynaecol. 2014.Google Scholar
  27. 27.
    Konopka T, Paradowska-Stolarz A. Periodontitis and risk of preterm birth and low birthweight–a meta-analysis. Ginekol Pol. 2012;83(6):446–53.PubMedGoogle Scholar
  28. 28.
    Boggess KA, Lieff S, Murtha AP, Moss K, Beck J, Offenbacher S. Maternal periodontal disease is associated with an increased risk for preeclampsia. Obstet Gynecol. 2003;101(2):227–31.PubMedGoogle Scholar
  29. 29.
    Koren O, Spor A, Felin J, Fak F, Stombaugh J, Tremaroli V, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A. 2011;15(108 Suppl 1):4592–8.CrossRefGoogle Scholar
  30. 30.
    Shillitoe E, Weinstock R, Kim T, Simon H, Planer J, Noonan S, et al. The oral microflora in obesity and type-2 diabetes. J Oral Microbiol. 2012;4.Google Scholar
  31. 31.
    Satokari R, Gronroos T, Laitinen K, Salminen S, Isolauri E. Bifidobacterium and Lactobacillus DNA in the human placenta. Lett Appl Microbiol. 2009;48(1):8–12.CrossRefPubMedGoogle Scholar
  32. 32.
    Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Science translational medicine. 2014 May 21;6(237):237ra65.Google Scholar
  33. 33.
    Prince AL, Ma J, Kannan PS, Alvarez M, Gisslen T, Harris RA, et al. The placental microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis. Am J Obstet Gynecol. 2016.Google Scholar
  34. 34.
    Antony KM, Ma J, Mitchell KB, Racusin DA, Versalovic J, Aagaard K. The preterm placental microbiome varies in association with excess maternal gestational weight gain. Am J Obstet Gynecol. 2015;212(5):653.e1–16.Google Scholar
  35. 35.
    Zheng J, Xiao X, Zhang Q, Mao L, Yu M, Xu J. The placental microbiome varies in association with low birth weight in full-term neonates. Nutrients. 2015;7(8):6924–37.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Sisti G, Kanninen TT, Witkin SS. Maternal immunity and pregnancy outcome: focus on preconception and autophagy. Genes Immun. 2016;17(1):1–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Schultz M, Gottl C, Young RJ, Iwen P, Vanderhoof JA. Administration of oral probiotic bacteria to pregnant women causes temporary infantile colonization. J Pediatr Gastroenterol Nutr. 2004;38(3):293–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971–5.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Prince AL, Antony KM, Ma J, Aagaard KM. The microbiome and development: a mother’s perspective. Semin Reprod Med. 2014;32(1):14–22.CrossRefPubMedGoogle Scholar
  40. 40.
    Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. 2016;22(3):250–3.Google Scholar
  41. 41.
    Madan JC, Farzan SF, Hibberd PL, Karagas MR. Normal neonatal microbiome variation in relation to environmental factors, infection and allergy. Curr Opin Pediatr. 2012;24(6):753–9.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Thompson AL. Developmental origins of obesity: early feeding environments, infant growth, and the intestinal microbiome. Am J Hum Biol. 2012;24(3):350–60.Google Scholar
  43. 43.
    Luoto R, Kalliomaki M, Laitinen K, Delzenne NM, Cani PD, Salminen S, et al. Initial dietary and microbiological environments deviate in normal-weight compared to overweight children at 10 years of age. J Pediatr Gastroenterol Nutr. 2011;52(1):90–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Collado MC, Laitinen K, Salminen S, Isolauri E. Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr Res. 2012;72(1):77–85.CrossRefPubMedGoogle Scholar
  45. 45.
    Hu J, Nomura Y, Bashir A, Fernandez-Hernandez H, Itzkowitz S, Pei Z, et al. Diversified microbiota of meconium is affected by maternal diabetes status. PLoS ONE. 2013;8(11):e78257.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Gosalbes MJ, Llop S, Valles Y, Moya A, Ballester F, Francino MP. Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants. Clin Exp Allergy. 2013;43(2):198–211.CrossRefPubMedGoogle Scholar
  47. 47.
    Griffin C. Probiotics in obstetrics and gynaecology. Aust N Z J Obstet Gynaecol. 2015;55(3):201–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Kankainen M, Paulin L, Tynkkynen S, von Ossowski I, Reunanen J, Partanen P, et al. Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human-mucus binding protein. Proc Natl Acad Sci. 2009;106(40):17193–8.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Lahti L, Salonen A, Kekkonen RA, Salojarvi J, Jalanka-Tuovinen J, Palva A, et al. Associations between the human intestinal microbiota, Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data. PeerJ. 2013;1:e32.Google Scholar
  50. 50.
    Palaria A, Johnson-Kanda I, O’Sullivan DJ. Effect of a synbiotic yogurt on levels of fecal bifidobacteria, clostridia, and enterobacteria. Appl Environ Microbiol. 2012;78(4):933–40.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    McNulty NP, Yatsunenko T, Hsiao A, Faith JJ, Muegge BD, Goodman AL, et al. The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins. Sci Trans Med. 2011;3(106):106ra-ra.Google Scholar
  52. 52.
    Barrett Helen L, Dekker Nitert M, Conwell Louise S, Callaway Leonie K. Probiotics for preventing gestational diabetes. Cochrane Database of Systematic Reviews [serial on the Internet]. 2012;(7): Available from:
  53. 53.
    Stone LP, Stone PM, Rydbom EA, Stone LA, Stone TE, Wilkens LE, et al. Customized nutritional enhancement for pregnant women appears to lower incidence of certain common maternal and neonatal complications: an observational study. Glob Adv Health Med. 2014;3(6):50–5.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Rogozinska E, Chamillard M, Hitman GA, Khan KS, Thangaratinam S. Nutritional manipulation for the primary prevention of gestational diabetes mellitus: a meta-analysis of randomised studies. PLoS ONE. 2015;10(2):e0115526.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Laitinen K, Poussa T, Isolauri E. Probiotics and dietary counselling contribute to glucose regulation during and after pregnancy: a randomised controlled trial. Br J Nutr. 2009;101(11):1679–87.CrossRefPubMedGoogle Scholar
  56. 56.
    Nitert MD, Barrett HL, Foxcroft K, Tremellen A, Wilkinson S, Lingwood B, et al. SPRING: an RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women. BMC Pregnancy Childbirth. 2013;13:50.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Asemi Z, Samimi M, Tabassi Z, Naghibi Rad M, Rahimi Foroushani A, Khorammian H, et al. Effect of daily consumption of probiotic yoghurt on insulin resistance in pregnant women: a randomized controlled trial. Eur J Clin Nutr. 2013;67(1):71–4.CrossRefPubMedGoogle Scholar
  58. 58.
    Lindsay KL, Kennelly M, Culliton M, Smith T, Maguire OC, Shanahan F, et al. Probiotics in obese pregnancy do not reduce maternal fasting glucose: a double-blind, placebo-controlled, randomized trial (Probiotics in Pregnancy Study). Am J Clin Nutr. 2014;99(6):1432–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Lindsay KL, Brennan L, Kennelly MA, Maguire OC, Smith T, Curran S, et al. Impact of probiotics in women with gestational diabetes mellitus on metabolic health: a randomized controlled trial. Am J Obstet Gynecol. 2015;212(4):496.e1–11.Google Scholar
  60. 60.
    Dolatkhah N, Hajifaraji M, Abbasalizadeh F, Aghamohammadzadeh N, Mehrabi Y. Mesgari Abbasi M. Is there a value for probiotic supplements in gestational diabetes mellitus? A randomized clinical trial. J Health Popul Nutr. 2015;33(1):25.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Vitali B, Ndagijimana M, Cruciani F, Carnevali P, Candela M, Guerzoni EM, et al. Impact of a synbiotic food on the gut microbial ecology and metabolic profiles. BMC Microbiol. 2010;10(1):1–13.Google Scholar
  62. 62.
    Taghizadeh M, Asemi Z. Effects of synbiotic food consumption on glycemic status and serum hs-CRP in pregnant women: a randomized controlled clinical trial. Hormones. 2014;13(3):398–406.Google Scholar
  63. 63.
    Taghizadeh M, Hashemi T, Shakeri H, Abedi F, Sabihi SS, Alizadeh SA, et al. Synbiotic food consumption reduces levels of triacylglycerols and VLDL, but not cholesterol, LDL, or HDL in plasma from pregnant women. Lipids. 2014;49(2):155–61.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Luisa F. Gomez Arango
    • 1
  • Helen L. Barrett
    • 1
  • Leonie K. Callaway
    • 2
  • H. David McIntyre
    • 3
  • Marloes Dekker Nitert
    • 1
    Email author
  1. 1.School of Medicine, The UQ Centre for Clinical ResearchThe University of QueenslandHerstonAustralia
  2. 2.Faculty of Medicine, School of Medicine, RBWH Clinical School, The UQ Centre for Clinical ResearchThe University of QueenslandHerstonAustralia
  3. 3.School of Medicine, Mater Clinical SchoolThe University of QueenslandSouth BrisbaneAustralia

Personalised recommendations