Microbiota of the Female Reproductive System

Abstract

The detailed evaluation of the members of the vast communities of microorganisms that inhabit our bodies has started with the microbiome project. Therefore, the microorganism fl ora inside the female reproductive system has been examined in terms of reproductive health, pregnancy and newborn health. New data obtained from the evaluation of microorganisms in the female reproductive system by performing studies from a different perspective will help us to understand the contribution of these microorganisms to health and diseases to provide information on future individual therapies. In this review, the effects of the changes in the microbiome of the female reproductive system on infertility, pregnancy and newborn will be evaluated in terms of their potential effects and applications in clinical practice.

Keywords

• Microbiota,Reproductive System,Vaginal Microbiota,İnfertility,Pregnancy,Newborn

Kadın Üreme Sistemi Mikrobiyotası

Abstract

Mikrobiyom projesi ile vücudumuzdaki büyük mikroorganizma fl orası üyelerinin detaylandırılması yapılmaya başlanmıştır. Bu bağlamda kadın üreme sisteminde yer alan mikroorganizma fl orası da üreme sağlığı, gebelik ve yenidoğan sağlığı yönünden yeniden ele alınmıştır. Kadın üreme sistemindeki mikroorganizmaların farklı bakış açısıyla incelenmesiyle yapılan araştırmalar sayesinde, elde olunan yeni bilgilerin bireylerde sağlık ve hastalık oluşumuna katkıları ve gelecekte buna yönelik yeni tedavi yöntemlerinin planlanması mümkün olabilecektir. Derlemede kadın üreme sistemi mikrobiyomunda saptanan değişimlerin infertilite, gebelik ve yenidoğan yönünden olası potansiyel etkilerinden ve klinik pratiğindeki uygulamalarından bahsedilecektir.

Keywords

• Mikrobiyota,Üreme Sistemi,Vajinal Mikrobiyota,İnfertilite,Gebelik,Yenidoğan

References

1. 1. Grice EA, Kong HH, Conlan S, Deming CB, Davis J, Young AC; NISC Comparative Sequencing Program, Bouffard GG, Blakesley RW, Murray PR, Green ED, Turner ML, Segre JA. Topographical and temporal diversity of the human skin microbiome. Science. 2009;324(5931):1190-2.
2. 2. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial fl ora. Science.2005;308(5728):1635-8.
3. 3. Nasidze I, Li J, Quinque D, Tang K, Stoneking M. Global diversity in the human salivary microbiome. Genome Res. 2009;19(4):636- 43.
4. 4. Oakley BB, Fiedler TL, Marrazzo JM, Fredricks DN. Diversity of Human Vaginal Bacterial Communities and Associations with Clinically Defi ned Bacterial Vaginosis. Applied and Environmental Microbiology. 2008;74(15):4898-4909.
5. 5. Relman DA. The Human Microbiome and the Future Practice of Medicine. JAMA. 2015;314(11):1127-8.
6. 6. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA. 2011;108 Suppl 1:4680-7.
7. 7. Priestley CJ, Jones BM, Dhar J, Goodwin L. What is normal vaginal fl ora? Genitourin Med. 1997;73(1):23-8.
8. 8. Schwebke JR, Richey CM, Weiss2 HL. Correlation of behaviors with microbiological changes in vaginal fl ora. J Infect Dis. 1999;180(5):1632-6.

9. 9. Mirmonsef P, Hotton AL, Gilbert D, Gioia CJ, Maric D, Hope TJ, Landay AL, Spear GT. Glycogen Levels in Undiluted Genital Fluid and Their Relationship to Vaginal pH, Estrogen, and Progesterone. PLoS One. 2016;11(4):e0153553.
10. 10. Hickey RJ, Zhou X, Settles ML, Erb J, Malone K, Hansmann MA, Shew ML, Van Der Pol B, Fortenberry JD, Forney LJ. Vaginal microbiota of adolescent girls prior to the onset of menarche resemble those of reproductive-age women. MBio. 2015;6(2).
11. 11. Eschenbach DA, Thwin SS, Patton DL, Hooton TM, Stapleton AE, Agnew K, Winter C, Meier A, Stamm WE. Infl uence of the normal menstrual cycle on vaginal tissue, discharge, and microfl ora. Clin Infect Dis. 2000;30(6):901-7.
12. 12. Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause. 2014;21(5):450-8.
13. 13. Borges S, Silva J, Teixeira P. The role of lactobacilli and probiotics in maintaining vaginal health. Arch Gynecol Obstet. 2014;289(3):479- 89.Review.
14. 14. Machado A, Salgueiro D, Harwich M, Jefferson KK, Cerca N. Quantitative analysis of initial adhesion of bacterial vaginosisassociated anaerobes to ME-180 cells. Anaerobe. 2013;23:1-4.
15. 15. Mastromarino P, Brigidi P, Macchia S, Maggi L, Pirovano F, Trinchieri V, Conte U, Matteuzzi D. Characterization and selection of vaginal Lactobacillus strains for the preparation of vaginal tablets. J Appl Microbiol. 2002;93(5):884-93.
16. 16. Boskey ER, Cone RA, Whaley KJ, Moench TR. Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum Reprod.2001;16(9):1809-13.
17. 17. Aroutcheva A, Gariti D, Simon M, Shott S, Faro J, Simoes JA, Gurguis A, Faro S. Defense factors of vaginal lactobacilli. Am J Obstet Gynecol. 2001;185(2):375-9.
18. 18. Machado D, Castro J, Palmeira-de-Oliveira A, Martinez-de-Oliveira J, Cerca N.Bacterial Vaginosis Biofi lms: Challenges to Current Therapies and Emerging Solutions. Front Microbiol. 2016;6:1528.
19. 19. Nelson DB, Hanlon A, Nachamkin I, Haggerty C, Mastrogiannis DS, Liu C,Fredricks DN. Early pregnancy changes in bacterial vaginosis-associated bacteria and preterm delivery. Paediatr Perinat Epidemiol. 2014;28(2):88-96.
20. 20. Kenyon C, Colebunders R, Crucitti T. The global epidemiology of bacterial vaginosis: a systematic review. Am J Obstet Gynecol. 2013 Dec;209(6):505-23.
21. 21. Taylor BD, Darville T, Haggerty CL. Does bacterial vaginosis cause pelvic infl ammatory disease? Sex Transm Dis. 2013 Feb;40(2):117- 22.
22. 22. Beruchashvili M, Gogiashvili L, Datunashvili E, Topuria Z, Tsagareli Z. Morphological peculiarities of endometrium in chronic endometritis associated with bacterial vaginosis. Georgian Med News. 2010;(181):59-63.
23. 23. Cu-Uvin S, Hogan JW, Caliendo AM, Harwell J, Mayer KH, Carpenter CC; HIV Epidemiology Research Study. Association between bacterial vaginosis and expression of human immunodefi ciency virus type 1 RNA in the female genital tract. Clin Infect Dis. 2001;33(6):894-6.
24. 24. Cherpes TL, Melan MA, Kant JA, Cosentino LA, Meyn LA, Hillier SL. Genital tract shedding of herpes simplex virus type 2 in women: effects of hormonal contraception, bacterial vaginosis, and vaginal group B Streptococcus colonization. Clin Infect Dis. 2005;40(10):1422-8.
25. 25. 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.
26. 26. Li J, McCormick J, Bocking A, Reid G. Importance of vaginal microbes in reproductive health. Reprod Sci. 2012;19(3):235-42.
27. 27. Eckert LO, Moore DE, Patton DL, Agnew KJ, Eschenbach DA. Relationship of vaginal bacteria and infl ammation with conception and early pregnancy loss following in-vitro fertilization. Infect Dis Obstet Gynecol. 2003;11(1):11-7.
28. 28. van Oostrum N, De Sutter P, Meys J, Verstraelen H. Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis. Hum Reprod. 2013;28(7):1809-15.
29. 29. Salah RM, Allam AM, Magdy AM, Mohamed ASh. Bacterial vaginosis and infertility: cause or association? Eur J Obstet Gynecol Reprod Biol. 2013;167(1):59-63.
30. 30. Haahr T, Jensen JS, Thomsen L, Duus L, Rygaard K, Humaidan P. Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients. Hum Reprod. 2016;31(4):795-803.
31. 31. Borgdorff H, Verwijs MC, Wit FW, Tsivtsivadze E, Ndayisaba GF, Verhelst R, Schuren FH, van de Wijgert JH. The impact of hormonal contraception and pregnancy on sexually transmitted infections and on cervicovaginal microbiota in african sex workers. Sex Transm Dis. 2015;42(3):143-52.
32. 32. Dareng EO, Ma B, Famooto AO, Adebamowo SN, Offi ong RA, Olaniyan O, Dakum PS,Wheeler CM, Fadrosh D, Yang H, Gajer P, Brotman RM, Ravel J, Adebamowo CA. Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women. Epidemiol Infect. 2016;144(1):123-37.
33. 33. Mitra A, MacIntyre DA, Lee YS, Smith A, Marchesi JR, Lehne B, Bhatia R, Lyons D, Paraskevaidis E, Li JV, Holmes E, Nicholson JK, Bennett PR, Kyrgiou M.Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci Rep. 2015;5:16865.
34. 34. Mayer BT, Srinivasan S, Fiedler TL, Marrazzo JM, Fredricks DN,Schiffer JT. Rapid and Profound Shifts in the Vaginal Microbiota Following Antibiotic Treatment for Bacterial Vaginosis. J Infect Dis. 2015;212(5):793-802.
35. 35. Vicariotto F, Mogna L, Del Piano M. Effectiveness of the two microorganisms Lactobacillus fermentum LF15 and Lactobacillus plantarum LP01, formulated in slow-release vaginal tablets, in women affected by bacterial vaginosis: a pilot study. J Clin Gastroenterol. 2014;48 Suppl 1:S106-12.
36. 36. Bradshaw CS, Pirotta M, De Guingand D, Hocking JS, Morton AN, Garland SM,Fehler G, Morrow A, Walker S, Vodstrcil LA, Fairley CK. Effi cacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial. PLoS One.2012;7(4):e34540.
37. 37. Falagas M, Betsi GI, Athanasiou S. Probiotics for the treatment of women with bacterial vaginosis. Clin Microbiol Infect. 2007;13(7):657-64. Review.
38. 38. Recine N, Palma E, Domenici L, Giorgini M, Imperiale L, Sassu C, Musella A,Marchetti C, Muzii L, Benedetti Panici P. Restoring vaginal microbiota: biological control of bacterial vaginosis. A prospective case-control study using Lactobacillus rhamnosus BMX 54 as adjuvant treatment against bacterial vaginosis. Arch Gynecol Obstet. 2016;293(1):101-7.
39. 39. Nelson DE, Dong Q, Van der Pol B, Toh E, Fan B, Katz BP, Mi D, Rong R, Weinstock GM, Sodergren E, Fortenberry JD. Bacterial communities of the coronal sulcus and distal urethra of adolescent males. PLoS One. 2012;7(5):e36298.
40. 40. Schwebke JR, Desmond RA. A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis. Clin Infect Dis. 2007;44(2):213-9.
41. 41. Cruciani F, Biagi E, Severgnini M, Consolandi C, Calanni F, Donders G, Brigidi P, Vitali B. Development of a microarray-based tool to characterize vaginal bacterial fl uctuations and application to a novel antibiotic treatment for bacterial vaginosis. Antimicrob Agents Chemother. 2015;59(5):2825-34.
42. 42. Reid G, Brigidi P, Burton JP, Contractor N, Duncan S, Fargier E, Hill C, Lebeer S, Martín R, McBain AJ, Mor G, O'Neill C, Rodríguez JM, Swann J, van Hemert S, Ansell J. Microbes central to human reproduction. Am J Reprod Immunol. 2015;73(1):1-11.
43. 43. Pelzer ES, Allan JA, Waterhouse MA, Ross T, Beagley KW, Knox CL. Microorganisms within human follicular fl uid: effects on IVF. PLoS One.2013;8(3):e59062.
44. 44. Barbonetti A, Cinque B, Vassallo MR, Mineo S, Francavilla S, Cifone MG, Francavilla F. Effect of vaginal probiotic lactobacilli on in vitroinduced sperm lipid peroxidation and its impact on sperm motility and viability. Fertil Steril.2011;95(8):2485-8.
45. 45. Escherich T. The intestinal bacteria of the neonate and breast-fed infant.1885. Rev Infect Dis. 1989;11(2):352-6.
46. 46. Jones HE, Harris KA, Azizia M, Bank L, Carpenter B, Hartley JC, Klein N, Peebles D. Differing prevalence and diversity of bacterial species in fetal membranes from very preterm and term labor. PLoS One. 2009;4(12):e8205.
47. 47. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65.
48. 48. Jiménez E, Marín ML, Martín R, Odriozola JM, Olivares M, Xaus J, Fernández L, Rodríguez JM. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159(3):187-93.
49. 49. Wassenaar TM, Panigrahi P. Is a foetus developing in a sterile environment? Lett Appl Microbiol. 2014;59(6):572-9.
50. 50. Funkhouser LJ, Bordenstein SR. Mom knows best: the universality of maternal microbial transmission. PLoS Biol. 2013;11(8):e1001631.
51. 51. Perez-Muñoz ME, Arrieta MC, Ramer-Tait AE, Walter J. A critical assessment of the "sterile womb" and "in utero colonization" hypotheses: implications for research on the pioneer infant microbiome. Microbiome. 2017;5(1):48.
52. 52. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015;31(1):69-75.
53. 53. Matamoros S, Gras-Leguen C, Le Vacon F, Potel G, de La Cochetiere MF. Development of intestinal microbiota in infants and its impact on health. Trends Microbiol. 2013;21(4):167-73.
54. 54. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–7.
55. 55. Di Gioia D, Aloisio I, Mazzola G, Biavati B. Bifi dobacteria: their impact on gut microbiota composition and their applications as probiotics in infants. Appl Microbiol Biotechnol. 2014;98(2):563–77.
56. 56. Dominguez-Bello, M.G., Costello, E.K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., Knight, R., 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. U. S. A. 107, 11971–11975.
57. 57. Black M, Bhattacharya S, Philip S, Norman JE, McLernon DJ. Planned Cesarean Delivery at Term and Adverse Outcomes in Childhood Health. JAMA. 2015;314(21):2271–9.
58. 58. Kuhle S, Tong OS, Woolcott CG. Association between caesarean section and childhood obesity: a systematic review and metaanalysis. Obes Rev. 2015;16(4):295–303.
59. 59. Adlercreutz EH, Wingren CJ, Vincente RP, Merlo J, Agardh D. Perinatal risk factors increase the risk of being affected by both type 1 diabetes and coeliac disease. Acta Paediatr. 2015;104(2):178–84.
60. 60. Kuhle S, Tong OS, Woolcott CG. Association between caesarean section and childhood obesity: a systematic review and metaanalysis. Obes Rev. 2015;16(4):295–303.
61. 61. Adlerberth I, Strachan DP, Matricardi PM, Ahrne S, Orfei L, Aberg N, Perkin MR, Tripodi S, Hesselmar B, Saalman R, et al. Gut microbiota and development of atopic eczema in 3 European birth cohorts. J Allergy Clin Immunol. 2007;120(2):343–50.
62. 62. Neu J, Rushing J. Cesarean versus vaginal delivery: long-term infant outcomes and the hygiene hypothesis. Clin Perinatol. 2011;38(2):321–31.
63. 63. Betran AP, Merialdi M, Lauer JA, Bing-Shun W, Thomas J, Van Look P, Wagner M. Rates of caesarean section: analysis of global, regional and national estimates. Paediatr Perinat Epidemiol. 2007;21(2):98– 113.
64. 64. Liu D, Yu J, Li L, Ai Q, Feng J, Song C, Li H. Bacterial community structure associated with elective cesarean section versus vaginal delivery in Chinese newborns. J Pediatr Gastr Nutr. 2015;60(2):240–6.
65. 65. Rutayisire E, Huang K, Liu Y, Tao F. The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the fi rst year of infants' life: a systematic review. BMC Gastroenterol. 2016;16(1):86.
66. 66. Mitsou EK, Kirtzalidou E, Oikonomou I, Liosis G, Kyriacou A. Fecal microfl ora of Greek healthy neonates. Anaerobe. 2008;14(2):94– 101.
67. 67. Gronlund MM, Lehtonen OP, Eerola E, Kero P. Fecal microfl ora in healthy infants born by different methods of delivery: permanent changes in intestinal fl ora after cesarean delivery. J Pediatr Gastroenterol Nutr. 1999; 28(1):19–25.
68. 68. Bezirtzoglou E. The intestinal microfl ora during the fi rst weeks of life. Anaerobe. 1997;3(2–3):173–7.
69. 69. Nagpal R, Tsuji H, Takahashi T, Kawashima K, Nagata S, Nomoto K, Yamashiro Y. Sensitive Quantitative Analysis of the Meconium Bacterial Microbiota in Healthy Term Infants Born Vaginally or by Cesarean Section. Front Microbiol. 2016;7:1997.
70. 70. Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6(11):e280.
71. 71. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, van den Brandt PA, Stobberingh EE. Factors infl uencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006;118(2):511–21.
72. 72. Stokholm J, Schjørring S, Pedersen L, Bischoff AL, Følsgaard N, Carson CG, Chawes BL, Bønnelykke K, Mølgaard A, Krogfelt KA, Bisgaard H. Prevalence and predictors of antibiotic administration during pregnancy and birth. PLoS One.2013;8(12):e82932.
73. 73. Cho I, Yamanishi S, Cox L, Methé BA, Zavadil J, Li K, Gao Z, Mahana D, Raju K, Teitler I, Li H, Alekseyenko AV, Blaser MJ. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488(7413):621-6.
74. 74. Azad MB, Konya T, Persaud RR, Guttman DS, Chari RS, Field CJ, Sears MR, Mandhane PJ, Turvey SE, Subbarao P, Becker AB, Scott JA, Kozyrskyj AL; CHILD Study Investigators. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the fi rst year of life: a prospective cohort study. BJOG. 2016;123(6):983-93.
75. 75. Mueller NT, Whyatt R, Hoepner L, Oberfi eld S, Dominguez-Bello MG, Widen EM, Hassoun A, Perera F, Rundle A. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. Int J Obes (Lond). 2015;39(4):665-70.
76. 76. Stensballe LG, Simonsen J, Jensen SM, Bønnelykke K, Bisgaard H. Use of antibiotics during pregnancy increases the risk of asthma in early childhood. J Pediatr 2013;162:832–838.e3.
77. 77. Virta L, Auvinen A, Helenius H, Huovinen P, Kolho KL. Association of repeated exposure to antibiotics with the development of pediatric Crohn’s disease–a nationwide, register-based fi nnish case-control study. Am J Epidemiol 2012;175:775–84.
78. 78. Perez PF, Dore J, Leclerc M, Levenez F, Benyacoub J, Serrant P, Segura- Roggero I, Schiffrin EJ, Donnet-Hughes A. Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics. 2007; 119(3):e724–732.
79. 79. Jeurink PV, van Bergenhenegouwen J, Jiménez E, Knippels LM, Fernández L,Garssen J, Knol J, Rodríguez JM, Martín R. Human milk: a source of more life than we imagine. Benef Microbes. 2013;4(1):17-30.
80. 80. Goulet O. Potential role of the intestinal microbiota in programming health and disease. Nutr Rev. 2015;73 Suppl 1:32–40.
81. 81. Underwood MA, German JB, Lebrilla CB, Mills DA. Bifi dobacterium longum subspecies infantis: champion colonizer of the infant gut. Pediatr Res. 2015; 77(1–2):229–35.
82. 82. Fallani M, Young D, Scott J, Norin E, Amarri S, Adam R, Aguilera M, Khanna S, Gil A, Edwards CA, Doré J; Other Members of the INFABIO Team. Intestinal microbiota of 6-week-old infants across Europe: geographic infl uence beyond delivery mode, breast-feeding, and antibiotics. J Pediatr Gastroenterol Nutr.2010;51(1):77-84.
83. 83. Bezirtzoglou E, Tsiotsias A, Welling GW. Microbiota profi le in feces of breast and formula-fed newborns by using fl uorescence in situ hybridization (FISH). Anaerobe. 2011;17(6):478–82.
84. 84. Penders J, Vink C, Driessen C, London N, Thijs C, Stobberingh EE. Quantifi cation of Bifi dobacterium spp., Escherichia coli and Clostridium diffi cile in faecal samples of breast-fed and formula-fed infants by real-time PCR. Fems Microbiol Lett. 2005;243(1):141–7.
85. 85. Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr 2012; 96:544–51.
86. 86. 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;72:77–85.
87. 87. Laitinen K, Collado MC, Isolauri E. Early nutritional environment: focus on health effects of microbiota and probiotics. Benef Microbes 2010;1:383–90.
88. 88. Bai DL, Wu KM, Tarrant M. Association between intrapartum interventions and breastfeeding duration. J Midwifery Womens Health. 2013;58(1):25–32.
89. 89. Martin R, Langa S, Reviriego C, Jiminez E, Marin ML, Xaus J, Fernandez L,Rodriguez JM. Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr. 2003;143(6):754–8.