The matter of the reproductive microbiome

Sam Schoenmakers, Regine Steegers-Theunissen, Marijke Faas, Sam Schoenmakers, Regine Steegers-Theunissen, Marijke Faas

Abstract

The preconceptional presence of microbiota in the female and male reproductive organs suggests that fertilization is taking place in a nonsterile environment and contributes to reproductive success. The concept of embryonic development in a sterile uterus has also been challenged with recent reports of the existence of a microbiome of the placenta, amniotic fluid and the fetal gut in normal, uncomplicated pregnancies. The maternal origins of the microbiota colonising the fetus and its surroundings are unknown as are the mechanisms of maternal-to-fetal transfer. In this review, we aim to highlight the preconception male and female microbiome, the maternal vaginal and gut microbiome during pregnancy and the fetal microbiome, including their possible roles in reproduction, and maternal and neonatal pregnancy outcome.

Keywords: Microbiome; embryo; maternal–fetal medicine; periconception; placenta; pregnancy.

Figures

Figure 1.
Figure 1.
Overview of the maternal and fetal microbiome during pregnancy, health effects and maternal–fetal microbiome axes.

References

    1. Romero R, Espinoza J, Goncalves LF, et al. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007; 25: 21–39.
    1. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486: 207–214.
    1. Verstraelen H, Vilchez-Vargas R, Desimpel F, et al. Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene. PeerJ 2016; 4: e1602.
    1. Aagaard K, Ma J, Antony KM, et al. The placenta harbors a unique microbiome. Sci Transl Med 2014; 6: 237ra65.
    1. Falony G, Joossens M, Vieira-Silva S, et al. Population-level analysis of gut microbiome variation. Science 2016; 352: 560–564.
    1. Flint HJ, Scott KP, Louis P, et al. The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol 2012; 9: 577–589.
    1. Maranduba CM, De Castro SB, de Souza GT, et al. Intestinal microbiota as modulators of the immune system and neuroimmune system: impact on the host health and homeostasis. J Immunol Res 2015; 2015: 931574.
    1. Knight R, Callewaert C, Marotz C, et al. The microbiome and human biology. Annu Rev Genomics Hum Genet 2017; 18: 65–86.
    1. Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature 2007; 449: 804–810.
    1. Collado MC, Rautava S, Aakko J, et al. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep 2016; 6: 23129.
    1. Hou D, Zhou X, Zhong X, et al. Microbiota of the seminal fluid from healthy and infertile men. Fertil Steril 2013; 100: 1261–1269.
    1. Gosalbes MJ, Llop S, Valles Y, et al. 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: 198–211.
    1. Moissl-Eichinger C, Auerbach AK, Probst AJ, et al. Quo vadis? Microbial profiling revealed strong effects of cleanroom maintenance and routes of contamination in indoor environments. Sci Rep 2015; 5: 9156.
    1. Grahn N, Olofsson M, Ellnebo-Svedlund K, et al. Identification of mixed bacterial DNA contamination in broad-range PCR amplification of 16S rDNA V1 and V3 variable regions by pyrosequencing of cloned amplicons. FEMS Microbiol Lett 2003; 219: 87–91.
    1. Salter SJ, Cox MJ, Turek EM, et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol 2014; 12: 87.
    1. Dasgupta S, Arya S, Choudhary S, et al. Amniotic fluid: source of trophic factors for the developing intestine. World J Gastrointest Pathophysiol 2016; 7: 38–47.
    1. Ardissone AN, de la Cruz DM, Davis-Richardson AG, et al. Meconium microbiome analysis identifies bacteria correlated with premature birth. PLoS One 2014; 9: e90784.
    1. Steegers-Theunissen RP, Twigt J, Pestinger V, et al. The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum Reprod Update 2013; 19: 640–655.
    1. Gohir W, Whelan FJ, Surette MG, et al. Pregnancy-related changes in the maternal gut microbiota are dependent upon the mother's periconceptional diet. Gut Microbes 2015; 6: 310–320.
    1. Pelzer ES, Allan JA, Cunningham K, et al. Microbial colonization of follicular fluid: alterations in cytokine expression and adverse assisted reproduction technology outcomes. Hum Reprod 2011; 26: 1799–1812.
    1. Pelzer ES, Allan JA, Waterhouse MA, et al. Microorganisms within human follicular fluid: effects on IVF. PLoS One 2013; 8: e59062.
    1. Moreno I, Codoner FM, Vilella F, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol 2016; 215: 684–703.
    1. Tachedjian G, Aldunate M, Bradshaw CS, et al. The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol 2017; 168: 782–792.
    1. Weng SL, Chiu CM, Lin FM, et al. Bacterial communities in semen from men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota to semen quality. PLoS One 2014; 9: e110152.
    1. Mandar R, Punab M, Borovkova N, et al. Complementary seminovaginal microbiome in couples. Res Microbiol 2015; 166: 440–447.
    1. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016; 106: 511–519.
    1. Gajer P, Brotman RM, Bai G, et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med 2012; 4: 132ra52.
    1. Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 2011; 108(Suppl 1): 4680–4687.
    1. Zhou X, Brown CJ, Abdo Z, et al. Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women. ISME J 2007; 1: 121–133.
    1. Fettweis JM, Brooks JP, Serrano MG, et al. Differences in vaginal microbiome in African American women versus women of European ancestry. Microbiology 2014; 160: 2272–2282.
    1. Hyman RW, Herndon CN, Jiang H, et al. The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer. J Assist Reprod Genet 2012; 29: 105–115.
    1. Feldt-Rasmussen U, Mathiesen ER. Endocrine disorders in pregnancy: physiological and hormonal aspects of pregnancy. Best Pract Res Clin Endocrinol Metab 2011; 25: 875–884.
    1. Newbern D, Freemark M. Placental hormones and the control of maternal metabolism and fetal growth. Curr Opin Endocrinol Diabetes Obes 2011; 18: 409–416.
    1. Aagaard K, Riehle K, Ma J, et al. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS One 2012; 7: e36466.
    1. DiGiulio DB, Callahan BJ, McMurdie PJ, et al. Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci U S A 2015; 112: 11060–11065.
    1. Hyman RW, Fukushima M, Jiang H, et al. Diversity of the vaginal microbiome correlates with preterm birth. Reprod Sci 2014; 21: 32–40.
    1. Romero R, Hassan SS, Gajer P, et al. The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Microbiome 2014; 2: 18.
    1. Walther-Antonio MR, Jeraldo P, Berg Miller ME, et al. Pregnancy's stronghold on the vaginal microbiome. PLoS One. 2014; 9: e98514.
    1. Stout MJ, Zhou Y, Wylie KM, et al. Early pregnancy vaginal microbiome trends and preterm birth. Am J Obstet Gynecol 2017; 217: 356 e1–356. e18.
    1. Romero R, Hassan SS, Gajer P, 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.
    1. Koren O, Goodrich JK, Cullender TC, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 2012; 150: 470–480.
    1. Collado MC, Isolauri E, Laitinen K, et al. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr 2008; 88: 894–899.
    1. Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol 2017; 17: 469–482.
    1. Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011; 334: 105–108.
    1. Antony KM, Ma J, Mitchell KB, et al. The preterm placental microbiome varies in association with excess maternal gestational weight gain. Am J Obstet Gynecol 2015; 212: 653.e1–616.
    1. Gomez-Arango LF, Barrett HL, McIntyre HD, et al. Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women. Sci Rep 2017; 7: 2860.
    1. Dobreva MP, Pereira PN, Deprest J, et al. On the origin of amniotic stem cells: of mice and men. Int J Dev Biol 2010; 54: 761–777.
    1. Ilancheran S, Moodley Y, Manuelpillai U. Human fetal membranes: a source of stem cells for tissue regeneration and repair? Placenta 2009; 30: 2–10.
    1. Huppertz B, Weiss G, Moser G. Trophoblast invasion and oxygenation of the placenta: measurements versus presumptions. J Reprod Immunol 2014; 101-102: 74–79.
    1. Jauniaux E, Watson AL, Hempstock J, et al. Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol 2000; 157: 2111–2122.
    1. Brosens I, Pijnenborg R, Vercruysse L, et al. The “Great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol 2011; 204: 193–201.
    1. Roberts JM. Pathophysiology of ischemic placental disease. Semin Perinatol 2014; 38: 139–145.
    1. Steegers EA, von Dadelszen P, Duvekot JJ, et al. Pre-eclampsia. Lancet 2010; 376: 631–644.
    1. Stout MJ, Conlon B, Landeau M, 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.e1–227.
    1. Parnell LA, Briggs CM, Cao B, et al. Microbial communities in placentas from term normal pregnancy exhibit spatially variable profiles. Sci Rep 2017; 7: 11200.
    1. Aagaard KM, Lahon A, Suter MA, et al. Primary human placental trophoblasts are permissive for Zika virus (ZIKV) replication. Sci Rep 2017; 7: 41389.
    1. Cao B, Mysorekar IU. Intracellular bacteria in placental basal plate localize to extravillous trophoblasts. Placenta 2014; 35: 139–142.
    1. Miner JJ, Cao B, Govero J, et al. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell 2016; 165: 1081–1091.
    1. Robbins JR, Skrzypczynska KM, Zeldovich VB, et al. Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes. PLoS Pathog 2010; 6: e1000732.
    1. Lauder AP, Roche AM, Sherrill-Mix S, et al. Comparison of placenta samples with contamination controls does not provide evidence for a distinct placenta microbiota. Microbiome 2016; 4: 29.
    1. McElrath TF, Hecht JL, Dammann O, et al. Pregnancy disorders that lead to delivery before the 28th week of gestation: an epidemiologic approach to classification. Am J Epidemiol 2008; 168: 980–989 00.
    1. Leviton A, Allred EN, Kuban KC, et al. Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. The ELGAN study. Pediatr Res 2010; 67: 95–101.
    1. Steel JH, Malatos S, Kennea N, et al. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res 2005; 57: 404–411.
    1. Jimenez E, Fernandez L, Marin ML, et al. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol 2005; 51: 270–274.
    1. Rodriguez N, Fernandez C, Zamora Y, et al. Detection of Ureaplasma urealyticum and Ureaplasma parvum in amniotic fluid: association with pregnancy outcomes. J Matern Fetal Neonatal Med 2011; 24: 47–50.
    1. Urushiyama D, Suda W, Ohnishi E, et al. Microbiome profile of the amniotic fluid as a predictive biomarker of perinatal outcome. Sci Rep 2017; 7: 12171.
    1. Greenough A. Factors adversely affecting lung growth. Paediatr Respir Rev 2000; 1: 314–320.
    1. Brace RA. Physiology of amniotic fluid volume regulation. Clin Obstet Gynecol 1997; 40: 280–289.
    1. Underwood MA, Gilbert WM, Sherman MP. Amniotic fluid: not just fetal urine anymore. J Perinatol 2005; 25: 341–348.
    1. Goldenberg RL, Culhane JF, Iams JD, et al. Epidemiology and causes of preterm birth. Lancet 2008; 371: 75–84.
    1. Thaler I, Manor D, Itskovitz J, et al. Changes in uterine blood flow during human pregnancy. Am J Obstet Gynecol 1990; 162: 121–125.
    1. Assali NS, Rauramo L, Peltonen T. Measurement of uterine blood flow and uterine metabolism. VIII. Uterine and fetal blood flow and oxygen consumption in early human pregnancy. Am J Obstet Gynecol 1960; 79: 86–98.
    1. Jimenez E, Marin ML, Martin R, et al. Is meconium from healthy newborns actually sterile? Res Microbiol 2008; 159: 187–193.
    1. Perez PF, Dore J, Leclerc M, et al. Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics 2007; 119: e724–e732.
    1. Donnet-Hughes A, Perez PF, Dore J, et al. Potential role of the intestinal microbiota of the mother in neonatal immune education. Proc Nutr Soc 2010; 69: 407–415.
    1. Uhlig HH, Powrie F. Dendritic cells and the intestinal bacterial flora: a role for localized mucosal immune responses. J Clin Invest 2003; 112: 648–651.
    1. Cobb CM, Kelly PJ, Williams KB, et al. The oral microbiome and adverse pregnancy outcomes. Int J Womens Health 2017; 9: 551–559.
    1. Pannu HK, Oliphant M. The subperitoneal space and peritoneal cavity: basic concepts. Abdom Imaging 2015; 40: 2710–2722.
    1. Emani R, Alam C, Pekkala S, et al. Peritoneal cavity is a route for gut-derived microbial signals to promote autoimmunity in non-obese diabetic mice. Scand J Immunol 2015; 81: 102–109.
    1. Kim MJ, Romero R, Gervasi MT, et al. Widespread microbial invasion of the chorioamniotic membranes is a consequence and not a cause of intra-amniotic infection. Lab Invest 2009; 89: 924–936.
    1. DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med 2012; 17: 2–11.
    1. Romero R, Quintero R, Oyarzun E, et al. Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes. Am J Obstet Gynecol 1988; 159: 661–666.
    1. Andrews WW, Goldenberg RL, Hauth JC, et al. Endometrial microbial colonization and plasma cell endometritis after spontaneous or indicated preterm versus term delivery. Am J Obstet Gynecol 2005; 193: 739–745.
    1. Biasucci G, Rubini M, Riboni S, et al. Mode of delivery affects the bacterial community in the newborn gut. Early Hum Dev 2010; 86: 13–15.
    1. Dominguez-Bello MG, Costello EK, Contreras M, 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: 11971–11975.
    1. Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, et al. The maternal microbiota drives early postnatal innate immune development. Science 2016; 351: 1296–1302.
    1. Wen L, Ley RE, Volchkov PY, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008; 455: 1109–1113.
    1. Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med 2016; 8: 39.
    1. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 2003; 361: 512–519.
    1. Stensballe LG, Simonsen J, Jensen SM, et al. Use of antibiotics during pregnancy increases the risk of asthma in early childhood. J Pediatr 2013; 162: 832–838.e3.
    1. Mueller NT, Whyatt R, Hoepner L, et al. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. Int J Obes 2015; 39: 665–670.
    1. Barker DJ. The fetal and infant origins of adult disease. BMJ 1990; 301: 1111.
    1. Racicot K, Cardenas I, Wunsche V, et al. Viral infection of the pregnant cervix predisposes to ascending bacterial infection. J Immunol 2013; 191: 934–941.
    1. Del Chierico F, Vernocchi P, Dallapiccola B and Putignani L. Mediterranean diet and health: food effects on gut microbiota and disease control. Int J Mol Sci 2014; 15: 11678–11699.
    1. Bartosch S, Fite A, Macfarlane GT and McMurdo ME. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol 2004; 70: 3575–3581.
    1. Santacruz A, Collado MC, Garcia-Valdes L, et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr 2010; 104: 83–92.
    1. Mueller NT, Shin H, Pizoni A, et al. Birth mode-dependent association between pre-pregnancy maternal weight status and the neonatal intestinal microbiome. Sci Rep 2016; 6: 23133.
    1. Blaut M. Gut microbiota and energy balance: role in obesity. Proc Nutr Soc 2015; 74: 227–234.
    1. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature 2009; 457: 480–484.
    1. Hu J, Nomura Y, Bashir A, et al. Diversified microbiota of meconium is affected by maternal diabetes status. PLoS One 2013; 8: e78257.
    1. Rautava S, Collado MC, Salminen S and Isolauri E. Probiotics modulate host-microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebo-controlled trial. Neonatology 2012; 102: 178–184.
    1. Vitali B, Cruciani F, Baldassarre ME, et al. Dietary supplementation with probiotics during late pregnancy: outcome on vaginal microbiota and cytokine secretion. BMC Microbiol 2012; 12: 236.
    1. Bassols J, Serino M, Carreras-Badosa G, et al. Gestational diabetes is associated with changes in placental microbiota and microbiome. Pediatr Res 2016; 80: 777–784.
    1. Prince AL, Ma J, Kannan PS, et al. The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis. Am J Obstet Gynecol 2016; 214: 627 e1–e16.
    1. Fujiwara N, Tsuruda K, Iwamoto Y, et al. Significant increase of oral bacteria in the early pregnancy period in Japanese women. J Investig Clin Dent 2017; 8.

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