The Reproductive Microbiome: Profound Implications of New Research

 In Fertility
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SARAH WYLIE, ND and JACLYN CHASSE-SMEATON, ND 

Once upon a time, I attended the birth of a patient in a teaching hospital in Vermont. The baby was born and crying healthfully at her mother’s breast, and it was time for the mother’s uterus to contract after delivering the placenta. Instinctively, forgetting I was in a hospital setting, I reached for the fundus to assess tone and gently remind her to contract. Immediately, the nurse standing opposite me scolded me for touching the patient and insisted, “This is a sterile field.” Because I was tired, I laughed out loud. I had seen feces, urine, amniotic fluid, and blood get dragged across this sterile field only moments earlier. There is very little that is sterile about natural childbirth. 

Many in the field of medicine devoted to childbirth and pediatrics have been working diligently to increase the incidence of vaginal birth over cesarean birth. One of the reasons we cite for promoting vaginal birth is to give the babies the best chance at having a healthy microbiome. We have long been taught that the womb is a sterile environment and that “seeding” of the gut microbiome in a newborn is accomplished primarily in the vaginal vault during delivery.   

New research suggests we were quite wrong. 

Seeding of the Fetal Microbiome 

Since about 2015, the research has been suggesting that the sterile womb hypothesis is incorrect and that the fetal microbiome is actually seeded from the placenta. A 2019 study by Younge et al studied mom/newborn dyads where the infants were born either preterm (prior to 24 weeks) or full term and born by cesarean.1 The study looked at oral and meconium microbiota, both of which are present in all newborns. The study demonstrated “a dynamic, viable mammalian fetal microbiota during in-utero development.”1 This observation that meconium contained its own unique microbiome clearly demonstrated that microbiota were present in the fetal gut, even in utero.   

The placenta, of course, offers the developing fetus the function of lungs, kidneys, liver, immune system, and gastrointestinal tract. This temporary organ – the size of a modest dinner plate – balances blood chemistry, supplies the fetus with nutrition, delivers oxygen and carbon dioxide back and forth, shares antibodies, and now, we realize, also forms the basis for the fetal microbiota.   

The mechanisms for seeding of the placental microbiome are not yet elucidated. However, it has been observed that the microbiota of the placenta most resembles the microbiome of a mother’s oral cavity and is influenced by the maternal periodontal microbiome, certain cytokines (interleukin [IL]-1ß, IL-6, IL-8, tumor necrosis factor [TNF]) and toll-like receptors (TLRs). The maternal oral microbiota is thus mirrored in the placental microbiota, when in turn informs the fetal microbiota.2  

The key driver of the infant microbiome, because it is tied to maternal oral health, is maternal diet in the 3rd trimester of pregnancy.3,4 This is tied primarily to dietary intake of prebiotics in the form of diverse fibers.5 Other factors include antibiotic use, obesity, presence of vaginal infection, and the presence of diabetes including gestational diabetes. 

In fact, the microbiota of an infant born vaginally to a mother with type 2 diabetes is less healthy than the microbiota of an infant born by cesarean to a mother without diabetes.6 The method of delivery – vaginal or cesarean – is less important for microbiome development because the microbiome of infants more or less coalesces around 6 weeks of age regardless of whether the mode of delivery was vaginal or surgical.6  

In the placental microbiome, Escherichia coli are the most prevalent bacterial species. There are limited species present overall. Beyond E coli, additional species include other EscherichiaBacteroidetesActinobacteriaProteobacteria, and Fusobacteria. Also unique to the placenta is the presence of Tenericutes.7  

The implications are that couples intending to have children may be able to greatly improve health outcomes of their children by investing in the health of their own microbiota. Additionally, physicians who encounter patients who experience surgical births can reassure them that the prior hypothesis – ie, that vaginal delivery is essential for colonization of their newborn’s microbiome – is incorrect, and they can provide reassurance and education that this in fact occurs within the womb. 

For women who experience cesarean births, the microbiome of the neonate (other than the gut microbiome) appears to depend on whether the mother labors or does not labor.6 In women who labor and then have a cesarean birth, the neonatal microbiome mirrors mom’s skin and vaginal microbiomes, which is the same outcome as when women deliver vaginally. However, for women who undergo a cesarean without laboring, the neonatal microbiome most resembles mom’s skin. In this study, microbiota also normalized by 6 weeks in all neonates regardless of birth style.6  

This study should instill confidence in practitioners in supporting women in their birthing choices, as well as provide reassurance to women who necessitate cesarean delivery. 

Practice Changes to Implement 

As part of preconception care, consider testing for group B Streptococcus and other dysbiotic microbes prior to conception. The therapies we use to alter the microbiome are more safely and efficiently utilized when a woman is not pregnant, as we lack evidence of safety in pregnancy for several botanicals that may be used as antimicrobials.  

Consider laboratory profiles to evaluate the microbiome of a woman’s oral cavity and/or vaginal vault. As discussed, a woman’s oral health becomes very important in pregnancy, given its prominent correlation with the placental microbiome. However, the vaginal microbiome also has a significant impact on the health of a pregnancy, including fertility and risk of miscarriage. Data demonstrate that vaginal microflora can also influence the placental microbiome.8,9 While these panels are offered in Europe, the panels currently available in the United States are not as comprehensive. However, there may be cases where they are still beneficial. 

The preconception period is the time to ensure proper oral and periodontal health. Dental work and periodontal cleanings should be conducted prior to, and not during, pregnancy. Preterm birth and low birth weight are associated with maternal periodontal disease, and levels of microbes in the mouth during pregnancy are naturally higher, particularly in early pregnancy.10,11 It is hypothesized that invasive bacteria in the mouth can cross into the blood stream and into the placenta. 

Additional methods for optimizing the oral microbiome in the mother include smoking cessation; brushing and flossing twice daily; avoiding alcohol-based, antiseptic mouthwashes; using gargles containing apple cider vinegar, salt, and essential oils such as thyme, tea tree, or lavender; oral probiotics; and increasing fiber and vegetables in the diet. 

The unique signature of each human comprises 100 trillion symbiotic microbes. Stated another way, there are more microbes in and on your body than there are stars in the Milky Way. Similar to the environmental devastation that humans have created on earth, the modern microbiome has suffered from the modern lifestyle. It is estimated by the Alimentary Pharmabiotic Centre in Ireland that 90% of health conditions can be linked to the health of the microbiome.12  

A rapidly expanding body of research has been identifying the importance of unique microbiomes in different parts of the body. Considering this new research highlighting the significance of the oral maternal microbiome in the seeding of the fetal microbiome, there is more reason than ever for women to attend to their oral health. 

References:

  1. Younge N, McCann JR, Ballard J, et al. Fetal exposure to the maternal microbiota in humans and mice. JCI Insight. 2019;4(19):e127806.   
  1. Prince AL, Antony KM, Chu DM, Aagaard KM. The microbiome, parturition, and timing of birth: more questions than answers. Reprod Immunol. 2014;104-105:12-19.  
  1. Chu DM, Antony KM, Ma J, et al. The early infant gut microbiome varies in association with a maternal high-fat diet. Genome Med. 2016;8(1):77.  
  1. Hu J, Nomura Y, Bashir A, et al. Diversified microbiota of meconium is affected by maternal diabetes status. PLoS One. 2013;8(11):e78257. 
  1. Pelzer E, Gomez-Arango LF, Barrett HL, Nitert MD. Review: Maternal health and the placental microbiome. Placenta. 2017;54:30-37.  
  1. Chu DM, Ma J, Prince AL, et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med. 2017;23(3):314-326. 
  1. Aagaard K, Ma J, Antony KM, et al. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65. 
  1. Onderdonk AB, Hecht JL, McElrath TF, et al. Colonization of second-trimester placenta parenchyma. Am J Obstet Gynecol. 2008;199(1):52.e1-52.e10. 
  1. Onderdonk AB, Delaney ML, DuBois AM, et al. Detection of bacteria in placental tissues obtained from extremely low gestational age neonates. Am J Obstet Gynecol. 2008;198(1):110.e1-e7. 
  1. Madianos PN, Bobetsis YA, Offenbacher S. Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms. Clin Periodontol. 2013;40 Suppl 14:S170-S180. 
  1. Fujiwara N, Tsuruda K, Iwamoto Y, et al. Significant increase of oral bacteria in the early pregnancy period in Japanese women. Investig Clin Dent. 2017;8(1). doi: 10.1111/jicd.12189.  
  1. APC, Microbiome Ireland. University College Cork, Ireland. Press Releases. Available at: https://apc.ucc.ie/news-events/press-releases/. Accessed November 2, 2020. 

Sarah Wylie, ND is a naturopathic physician with extra special training in fertility, childbirth, and mothering. She casts a bridge between the distinct arenas of ancient and modern philosophies. Dr Wylie is a functional medicine doctor, utilizing lab testing to offer a novel and specific approach to enhancing fertility. She has had a busy practice in women’s health physical medicine and is known locally in the Green Mountains of Vermont as “the Uterus Whisperer”.   

Jaclyn Chasse-Smeaton, ND, is a licensed naturopathic physician focused on infertility, reproductive, and genitourinary health. Her practice, Perfect Fertility, has helped thousands of couples grow their families, and her passion to share this knowledge has led her to teach integrative fertility care to thousands of doctors. Dr Smeaton also works as VP of Medical Education for Emerson Ecologics, the largest provider of vitamins and supplements into the medical community. Dr Smeaton is the past-president of the AANP, and has served on the boards of several organizations, including the Integrative Health Policy Consortium, the American Herbal Products Association, and many others.  

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