The Microbiome & Fertility

Are you thinking of having a baby in the next couple of months? Then start prepping your biome!

Most microbiome research is currently limited to the intestines (also known as the gut microbiome), which hosts the most diverse and abundant microbial community in the body (Bäckhed et al., 2012).

But we also harbour this microbial universe in other areas of our bodies such as the mouth, seminal fluid (if you are a man) and vagina. The state of our biome in all these areas is correlated to fertility, the success of conception, the health and maintenance of future pregnancies, pregnancy outcome, and eventually the health of the baby (Mysorekar & Cao, 2014).

How is that possible?

Well, for about a century, it has been assumed that the foetus is sterile and that microbes only colonise the new-born during birth (depending on the delivery mode) (Rodríguez et al., 2015).

But recent studies have shown that microbes actually colonise the amniotic fluid, the umbilical blood cord, and the placenta, suggesting that there is a maternal microbial colonisation of the foetus during pregnancy and before birth (Korpela et al., 2020; D’argenio, 2018).

The currently accepted theory of how this is happening originates from microbes travelling from the oral cavity, the gut, and the vagina to colonise the growing foetus and play a role in the baby’s physiological development.

As a consequence, a mother’s biome and early life factors in the first 2-3 years of life will have an influence on the baby’s microbiota development and composition (Mueller et al., 2015) . The state of the baby’s biome, in turn, impacts its future health.

In pregnancy, there is dramatic hormonal, metabolic, and immunologic shifts that occurs to support the growing baby. These shifts can alter an expectant’s mother own bacterial composition (Nuriel-Ohayon et al., 2016).

If the current microbiome (before pregnancy) is unbalanced or altered due to pre-existing physical or mental disruptions such as anxiety, eating disorders, unhealthy diet, or frequent antibiotic treatments, pregnancy will not only transfer these microbes to the baby, determining its first microbial makeup, but it will enhance a mother’s current biome’s imbalance. These alterations may even persist for as long as one year after delivery (DiGiulio et al., 2015).

That is why it is crucial to tackle any unhealthy imbalances of the microbiota in all areas of the body before getting pregnant, whether the cause is physical or emotional .

One of the ways to maximise fertility and implantation success, as well as the duration of pregnancy and the trajectory of foetal growth, is keeping the reproductive tract healthy and balanced.

The Uterine & Vaginal Microbiome

The “normal” microbiome of the vagina in non-pregnant healthy women is individual, changes drastically over a woman’s menstrual and lifecycle, and is ethnic related.

But predominantly it includes a variety of Lactobacillus species, which promotes a healthy and supportive environment for the embryo through the production of lactic acid and hydrogen peroxide (Sirota et al., 2014).

However, when the vaginal colony becomes unbalanced, acidity decreases. This creates an unfavourable environment, affecting sperm's transition and motility through the vaginal canal and promoting the growth of pathogenic bacteria. This disturbance can cause bacterial vaginosis— common symptoms include unusual discharge with a strong fishy smell, particularly after sex. 50% of women with vaginosis may display no obvious symptoms.

Several factors may affect the vaginal ecosystem, such as smoking, abnormal menstruation, stress, diet, the number of sexual partners, and obesity. Two of the most direct ways to upset the vaginal microbiome may be douching and the use of spermicides.

It may not seem significant, but vaginosis increases the risk of preterm birth, pelvic inflammatory disease, and contracting secondary infections from herpes to HIV (Petrova et al., 2015). These adverse conditions not only affect the person who has them but the baby too, in the case of a pregnant woman.

Even without these complications, the microbial shifts in vaginosis can cause low-grade inflammation that can hinder conception and cause infertility.

Recent research from the National Institutes of Health Human Microbiome Project found that in pregnant women, the vaginal microbiome before 24 weeks of gestation could provide a marker for a potential risk of premature birth. Women with particular vaginal microbiomes were more likely to experience spontaneous premature births at fewer than 37 weeks of pregnancy. One characteristic of these microbiomes was a lower abundance of Lactobacillus crispatus and an increase in Sneathia amnii, BVAB1, and a Saccharibacteria bacterium known as TM7-H1. Notably, these strains of microbes were also associated with low levels of vitamin D, suggesting a link between premature birth risk and vitamin D deficiency (Fettweis et al., 2019).

But the reproductive tract of a woman is not the only one relevant for conception and pregnancy.

The Testes & Seminal Fluid’s Microbiome

The male reproductive system harbors its own microbiome in the testes and the seminal fluid. Compared to its female counterpart, the microbiota of the male genital tract has not been studied extensively.

But previous research has found that the immune system, and subsequently infections, play a crucial role in the dynamics and changes in semen microbiota composition.

HIV infection, for example, was associated with decreased semen microbiome diversity and richness (Liu et al., 2014), while men with prostatitis often had infectious polymicrobial colonies in their semen in addition to a reduction in the relative abundance of the health-supporting microbe lactobacilli (Mändar et al., 2017).

Although microbe communities in men differed among studies, the most represented species were Prevotella, Staphylococcus, and Lactobacillus. These correlated with semen health in terms of motility and morphology, as well as fertility (Baud et al., 2019).

For example, the presence of Prevotella species has been associated with low-quality semen, while Lactobacillus predominance was associated with healthier semen (Mändar et al., 2015; Weng et al., 2014).

The best ways to optimise the microbiome of both parents are:

• Improving the diet. By eating more fermented and cultured foods that will introduce probiotics (good bacteria) to the biome of aspiring parents. Fermented foods will not only “reseed” the gut with health promoting microorganisms, but are outstanding sources of essential nutrients such as B vitamins and K2.

  They can also increase the bioavailability of minerals, and help you with detoxification. I would recommend adding a small amount of diverse fermented foods by using them as a condiments with daily meals, thus optimising the microbial diversity.

  There is also a need to provide nourishment for the existing beneficial microbes, by having fibre daily: it can serve as a prebiotic, providing good food for your probiotics.

  Like fermented foods, not all fibres behave the same way: there is a wide variation in their chemical compositions and their physicochemical properties. Therefore I recommend a diverse range of fibre sources of 25-35 g/ day to provide the most health benefits and support a more diverse microbiota composition.

• Supplementing with probiotics. Probiotic supplements can provide a boost to probiotic foods.

  Studies have shown that probiotic supplementation can reduce a baby’s risk of certain non-communicable diseases during pregnancy (Reid, 2016). But it seems wise to supplement before pregnancy, considering the key foetal developmental milestones that happen in the womb in the early weeks.

  When it comes to vaginal microbiome, Oral Lactobacillus rhamnosus and Lactobacillus fermentum supplementation have been shown to restore healthy vaginal flora in up to 82% of women with previous vaginal dysbiosis (García-Velasco et al., 2017) as well as reducing the risk of infection, subsequent inflammation, and immune dysfunction. This can be beneficial to fertility and conception.

  For men, research has found that supplementing with Lactobacillus brevis, Lactobacillus plantarum, and Lactobacillus salivarius preserved sperm motility and viability in vitro and supplementing with Lactobacillus reuteri may contribute to having more youthful testosterone levels which can translate into better overall sperm quality (Poutahidis et al., 2014; Barbonetti et al., 2013).

  Remember to look for quality brands with at least 10 billion (and preferably up to 100 billion) CFUs (colony forming units), and store the supplements as directed on the package.
  

• Avoiding antibiotics unless absolutely necessary. It can take up to two years for the microbiome to re-establish after just one course of antibiotics, and some strains will never recover (Jernberg et al., 2010).

  If a course of antibiotics have to be taken, eating cultured foods or taking a quality probiotic at the same time can help! But take them at least a few hours apart.
  

• Practicing good oral hygiene. Maternal oral health has a significant influence on pregnancy and childbirth because the mother's oral bacteria is transmitted to the new-born infant.

  Research now indicates that the uterus, placenta, and amniotic fluid are the baby's first source of microbes, and some research suggests that the microbiome of the placenta more closely resembles the microbiome of the mouth than that of the gut or vagina (Aagaard et al., 2014).

  This suggests that bacteria may pass from the oral cavity of the mother through the bloodstream to the placenta, explaining the many observations of maternal periodontal disease (chronic infections of the gums and the bone that supports the teeth) being correlated to increased risks of pregnancy complications such as preterm birth, preeclampsia, and delivery of a small-for-gestational age infant (Mysorekar & Cao, 2014; Prince et al., 2014).

  More good reason, then, to improve oral health care before your pregnancy whenever possible!

  One study has found that orally administered probiotic strains can also help! Lactobacillus reuteri can affect oral health by reducing the occurrence of both plaque and bleeding from the gums after 8 weeks (Iniesta et al., 2012).
  

• Practicing better birth control. It is important to be aware of any potential side effects your birth control method may have on the vaginal microbiota.

  One study showed that there was an increase of bacterial vaginosis in women with the copper IUD (Achilles et al., 2018).

  Spermicides can also have a negative effect on the vaginal microbiome, so contact the GP for any concerns.

References+

Aagaard, K., Ma, J., Antony, K. M., Ganu, R., Petrosino, J., & Versalovic, J. (2014). The placenta harbors a unique microbiome. Science Translational Medicine.

Achilles, S. L., Austin, M. N., Meyn, L. A., Mhlanga, F., Chirenje, Z. M., & Hillier, S. L. (2018). Impact of contraceptive initiation on vaginal microbiota. American Journal of Obstetrics and Gynecology.

Bäckhed, F., Fraser, C. M., Ringel, Y., Sanders, M. E., Sartor, R. B., Sherman, P. M., … Finlay, B. B. (2012). Defining a healthy human gut microbiome: Current concepts, future directions, and clinical applications. Cell Host and Microbe.

Barbonetti, A., Vassallo, M. R. C., Cinque, B., Filipponi, S., Mastromarino, P., Cifone, M. G., … Francavilla, F. (2013). Soluble products of Escherichia coli induce mitochondrial dysfunction-related sperm membrane lipid peroxidation which is prevented by lactobacilli. PLoS ONE.

Baud, D., Pattaroni, C., Vulliemoz, N., Castella, V., Marsland, B. J., & Stojanov, M. (2019). Sperm microbiota and its impact on semen parameters. Frontiers in Microbiology.

D’argenio, V. (2018). The prenatal microbiome: A new player for human health. High-Throughput.

DiGiulio, D. B., Callahan, B. J., McMurdie, P. J., Costello, E. K., Lyell, D. J., Robaczewska, A., … Relman, D. A. (2015). Temporal and spatial variation of the human microbiota during pregnancy. Proceedings of the National Academy of Sciences of the United States of America.

Fettweis, J. M., Serrano, M. G., Brooks, J. P., Edwards, D. J., Girerd, P. H., Parikh, H. I., … Buck, G. A. (2019). The vaginal microbiome and preterm birth. Nature Medicine.

García-Velasco, J. A., Menabrito, M., & Catalán, I. B. (2017). What fertility specialists should know about the vaginal microbiome: a review. Reproductive BioMedicine Online.

Iniesta, M., Herrera, D., Montero, E., Zurbriggen, M., Matos, A. R., Marín, M. J., … Sanz, M. (2012). Probiotic effects of orally administered Lactobacillus reuteri-containing tablets on the subgingival and salivary microbiota in patients with gingivitis. A randomizised clinical trial. Journal of Clinical Periodontology.

Jernberg, C., Löfmark, S., Edlund, C., & Jansson, J. K. (2010). Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology.

Korpela, K., Renko, M., Paalanne, N., Vänni, P., Salo, J., Tejesvi, M., Koivusaari, P., Pokka, T., Kaukola, T., Pirttilä, A.M., et al. (2020). Microbiome of the first stool after birth and infantile colic. Pediatric Research.

Liu, C. M., Osborne, B. J. W., Hungate, B. A., Shahabi, K., Huibner, S., Lester, R., … Kaul, R. (2014). The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection.

Mändar, R., Punab, M., Borovkova, N., Lapp, E., Kiiker, R., Korrovits, P., … Truu, J. (2015). Complementary seminovaginal microbiome in couples. Research in Microbiology.

Mändar, R., Punab, M., Korrovits, P., Türk, S., Ausmees, K., Lapp, E., … Truu, J. (2017). Seminal microbiome in men with and without prostatitis

Mueller, N. T., Bakacs, E., Combellick, J., Grigoryan, Z., & Dominguez-Bello, M. G. (2015). The infant microbiome development: Mom matters. Trends in Molecular Medicine.

Mysorekar, I. U., & Cao, B. (2014). Microbiome in parturition and preterm birth. Seminars in Reproductive Medicine.

Nuriel-Ohayon, M., Neuman, H., & Koren, O. (2016). Microbial changes during pregnancy, birth, and infancy. Frontiers in Microbiology.

Petrova, M. I., Lievens, E., Malik, S., Imholz, N., & Lebeer, S. (2015). Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Frontiers in Physiology.

Poutahidis, T., Springer, A., Levkovich, T., Qi, P., Varian, B.J., Lakritz, J.R., Ibrahim, Y.M., Chatzigiagkos, A., Alm, E.J., and Erdman, S.E. (2014). Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging mice. PLoS ONE 9.

Prince, A. L., Antony, K. M., Chu, D. M., & Aagaard, K. M. (2014). The microbiome, parturition, and timing of birth: More questions than answers. Journal of Reproductive Immunology.

Rodríguez, J. M., Murphy, K., Stanton, C., Ross, R. P., Kober, O. I., Juge, N., … Collado, M. C. (2015). The composition of the gut microbiota throughout life, with an emphasis on early life. Microbial Ecology in Health & Disease.

Sirota, I., Zarek, S. M., & Segars, J. H. (2014). Potential influence of the microbiome on infertility and assisted reproductive technology. Seminars in Reproductive Medicine.

Weng, S. L., Chiu, C. M., Lin, F. M., Huang, W. C., Liang, C., Yang, T., … Huang, H. Da. (2014). Bacterial communities in semen from men of infertile couples: Metagenomic sequencing reveals relationships of seminal microbiota to semen quality. PLoS ONE

DR NAUF ALBENDAR

My name is Dr Nauf AlBendar and I am the founder of The Womb Effect. As a medical scientist with a BSc in Molecular Genetics and Genomics, an MSc in Nutrition & Food Science and a PHD in clinical medicine, I have developed a deep appreciation and understanding for the developmental origins of health and disease.