Education

What does gut health have to do with hormone balance and infertility?

Jun 08, 2021

What does gut health have to do with hormone balance and infertility?

Gut health and dysbiosis are often overlooked factors among couples with infertility, diminished ovarian reserve, and premature ovarian failure/insufficiency. However, the science is clear that a leaky gut and the microbiome can contribute to infertility, even in people without digestive issues. This article will cover the latest science and what you can do to improve your gut health and maximize your chance of conceiving.

3 ways your gut and gut bacteria affect your hormone balance and fertility

You’re more bacteria than human, as the latest estimate suggests that an average human has ~39 trillion bacteria cells in our body, versus 30 trillion human cells [1]. The gut bacteria have the most diverse microbial composition, which affects all aspects of your health, especially hormonal health and fertility.

1) Metabolizing your hormones

Your gut bacteria work as an endocrine organ. They convert, activate, deactivate, and breakdown of different hormones, including estrogen and thyroid hormones [2, 3]. The combination of bacteria genes that metabolite your estrogen is called the estrobolome. 

Estrobolome - How gut bacteria modulates estrogens

How gut bacteria genes modulate estrogen metabolisms, influencing hormone balance and fertility. Source: Ervin SM et al (2019)

2) Vaginal and uterine microbial environment

How reproductive tract microbiome influences fertility and live birth rates

How reproductive tract microbiome influences fertility and live birth rates. Source: Rizzo et al (2019)

Your reproductive tract also has its own microbiome. Not surprisingly, the microbial compositions influence menstrual cycles, conception, and pregnancy, as they affect the local tissue health and immune responses [4]. 

Scientists are still trying to understand where the uterine microbiome comes from. The most likely explanation is that some white blood cells carry them from the gut to the uterus [5]. Therefore, vaginal and uterine dysbiosis tend to reflect gut dysbiosis. 

3) Immune balance, inflammation, and autoimmunity

About 80% of your immune system is in the gut, so gut health affects your immune balance. A healthy gut barrier is critical for healthy nutrient absorption and keeping the gut content inside the gut. 

A compromised gut barrier, or intestinal permeability, allows bacterial toxins such as lipopolysaccharides (LPS) and incompletely digested food fragments into the bloodstream, causing inflammation. LPS is a toxin found in the cell wall of Gram-negative bacteria, which is harmless inside the gut but toxic in the blood. However, we test for many of these bacteria, including Klebsiella, Actinobacter, and Pseudomonas in stool tests as having high Gram-negative bacteria is a sign of dysbiosis. Having LPS in the blood is linked to chronic low-grade inflammation that contributes to insulin resistance, obesity, diabetes, Alzheimer’s disease, high cholesterol, and more [6]. 

In people with tendencies for autoimmunity, food fragments can trigger autoimmunity based on molecular mimicry, or if the food proteins are sufficiently similar to some of their own tissues [7]. Many of our clients with low AMH and high FSH also have autoimmune issues.

Blood LPS, autoimmunity, and chronic inflammation can interfere with healthy hormone levels and fertility, even though you have no digestive problems. This post and podcast episode covers a list of symptoms that are linked to poor gut health and dysbiosis.

How gut bacteria and gut health affect reproductive conditions

Premenstrual syndrome and premenstrual dysphoric disorder

The composition of the gut microbiome and gut permeability change with the hormonal fluctuations over your menstrual cycle. Antibodies against LPS and certain Gram-negative gut bacteria peak during the late luteal phase, which corresponds to the PMS symptoms severity including both cramps and mood changes [8]. 

Therefore, pre-existing inflammation and poor gut health can result in worsened PMS. 

Endometriosis

Endometriosis is a debilitating condition where cells similar to the endometrial lining grow outside the uterus. Estrogen dominance, progesterone resistance, and chronic inflammation worsen endometriosis [9]. Symptoms of endometriosis may include severe menstrual pain, pelvic pain, excessive and prolonged menstrual bleeding, fertility problems, and recurrent miscarriages.

In a small clinical study with 8 endometriosis patients and 14 healthy controls, those with endometriosis had leakier gut and higher blood LPS levels. The higher LPS levels were associated with worsened pelvic pain [10].

Women with endometriosis are 3.26 times more likely to have irritable bowel syndrome than those without endometriosis [11,12]. Managing SIBO and IBS, such as with a low-FODMAPs diet, alleviated many symptoms of endometriosis [13]. 

The microbiome of women with endometriosis is higher in certain bacteria types, to the point that microbiome profiling might be useful for endometriosis staging [14-16].

PCOS

PCOS is associated with reduced bacteria diversity and some dysbiosis [17,18]. The number of different bacteria species of their gut microbiome is inversely correlated with their insulin resistance [17]. 

PCOS patients have more bacterial genes that disrupt tight junctions and increase metabolites that tend to irritate the gut, including acetaldehyde, hydrogen sulfide, and ammonia. Their gut bacteria also produce more LPS, break down the protective mucus in the gut more readily, and create more oxidative stress [18]. 

Undeniably, the gut microbiome strongly contributes to pathology and comorbidities of PCOS. In a rat model of PCOS, implanting the stool microbiome from healthy rats improved their menstrual cycles and ovarian morphology [19]. While we still don’t know if fecal microbiota transplant can cure PCOS in humans, it is definitely beneficial to improve the gut health and microbiome in PCOS. 

Thyroid conditions

Gut and gut microbiota health help with the absorption of all micronutrients that are important for thyroid function, including iodine, selenium, iron, zinc, and vitamin D. In addition, immune imbalances and leaky gut may trigger autoimmune thyroid diseases in susceptible people [20]. 

Infertility and Diminished Ovarian Reserve

Women with premature ovarian insufficiency have dysbiosis that correlates with low estrogen and AMH, and high FSH [21]. In an animal model, elevated LPS is associated with uterine impairment, embryonic resorption, ovarian dysfunction, and delayed follicle growth [22]. 

Healthy mitochondria are critical for oocyte quality, oocyte maturation, embryonic development, and pregnancy [23]. In addition, throughout reproductive aging, the mitochondria will start triggering apoptosis (cellular suicide), which eliminates low-quality oocytes and follicles. If enough apoptosis occurs, this can lead to premature ovarian failure and diminished ovarian reserve [24]. LPS and inflammation from leaky gut can increase reactive oxygen species that may interfere with the ovarian mitochondria function. 

Clinical studies have also found that certain patterns of reproductive tract microbiome influence fertility treatment outcomes. Disordered reproductive tract microbiomes have also been associated with IVF failure [25]. Whereas, the presence of Lactobacillus crispatus, a species associated with healthy vaginal flora, was associated with IUI success among couples with idiopathic infertility.

How to heal the gut for optimal hormone balance and fertility

As you can see, studies have shown that poor gut health, intestinal permeability, and dysbiosis contribute to many reproductive disorders and fertility problems. Conventional medical doctors are unlikely to diagnose and treat these issues. Currently, it is beyond their realm to address the gut. However, the good news is, you can improve your gut health and microbiome naturally. 

You need a comprehensive and targeted lifestyle program that addresses the root causes because gut and microbiome health are so intricate with all systems in the body. There is no one pill that you can take to fix all of them, and probiotic supplements alone rarely improve the microbiome and repair the gut lining enough to boost fertility. At FabFertile, we have been able to help hundreds of clients do so with the FabFertile method, which includes the 4R approach.

  1. Remove the root causes, which may differ from client to client. These may include:
    • Unhealthy diets with excessive bad fat and sugar
    • Foods that irritate the gut and cause inflammation, such as gluten and dairy
    • Mental-emotional stressors
    • Gut infections
    • Toxins and heavy metals 
  2. Replace the insufficient stomach acids and digestive enzymes to optimize digestion
  3. Reinoculate with the right bacteria strains that promote healthy gut microbiomes, along with feeding them with the right foods
  4. Repair the gut lining with the right supplement support with gut-nourishing nutrients such as the amino acid glutamine

Many of our clients with DOR and POI have been able to get pregnant after healing their guts and restoring healthy microbiomes. To learn more about how you can improve your chance of conceiving, book a free consultation here

References:

  1. Abbott A. Scientists bust myth that our bodies have more bacteria than human cells. Nature. 2016 [cited 4 Jun 2021]. doi:10.1038/nature.2016.19136
  2. Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe. 2011;10: 324–335.
  3. Kunc M, Gabrych A, Witkowski JM. Microbiome impact on metabolism and function of sex, thyroid, growth and parathyroid hormones. Acta Biochim Pol. 2016;63: 189–201.
  4. Bardos J, Fiorentino D, Longman RE, Paidas M. Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota. Front Immunol. 2019;10: 2823.
  5. Donnet-Hughes A, Perez PF, Doré J, Leclerc M, Levenez F, Benyacoub J, et al. Potential role of the intestinal microbiota of the mother in neonatal immune education. Proc Nutr Soc. 2010;69: 407–415.
  6. André P, Laugerette F, Féart C. Metabolic Endotoxemia: A Potential Underlying Mechanism of the Relationship between Dietary Fat Intake and Risk for Cognitive Impairments in Humans? Nutrients. 2019;11. doi:10.3390/nu11081887
  7. Vojdani A. Molecular mimicry as a mechanism for food immune reactivities and autoimmunity. Altern Ther Health Med. 2015;21 Suppl 1: 34–45.
  8. Roomruangwong C, Carvalho AF, Geffard M, Maes M. The menstrual cycle may not be limited to the endometrium but also may impact gut permeability. Acta Neuropsychiatr. 2019;31: 294–304.
  9. Patel BG, Rudnicki M, Yu J, Shu Y, Taylor RN. Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet Gynecol Scand. 2017;96: 623–632.
  10. Viganó D, Zara F, Pinto S, Loddo E, Casula L, Soru MB, et al. How is small bowel permeability in endometriosis patients? a case control pilot study. Gynecol Endocrinol. 2020;36: 1010–1014.
  11. Chiaffarino F, Cipriani S, Ricci E, Mauri PA, Esposito G, Barretta M, et al. Endometriosis and irritable bowel syndrome: a systematic review and meta-analysis. Arch Gynecol Obstet. 2021;303: 17–25.
  12. Schomacker ML, Hansen KE, Ramlau-Hansen CH, Forman A. Is endometriosis associated with irritable bowel syndrome? A cross-sectional study. Eur J Obstet Gynecol Reprod Biol. 2018;231: 65–69.
  13. Moore JS, Gibson PR, Perry RE, Burgell RE. Endometriosis in patients with irritable bowel syndrome: Specific symptomatic and demographic profile, and response to the low FODMAP diet. Aust N Z J Obstet Gynaecol. 2017;57: 201–205.
  14. Leonardi M, Hicks C, El-Assaad F, El-Omar E, Condous G. Endometriosis and the microbiome: a systematic review. BJOG. 2020;127: 239–249.
  15. D’Alterio MN, Giuliani C, Scicchitano F, Laganà AS, Oltolina NM, Sorrentino F, et al. Possible role of microbiome in the pathogenesis of endometriosis. Minerva Obstet Gynecol. 2021;73: 193–214.
  16. Perrotta AR, Borrelli GM, Martins CO, Kallas EG, Sanabani SS, Griffith LG, et al. The Vaginal Microbiome as a Tool to Predict rASRM Stage of Disease in Endometriosis: a Pilot Study. Reprod Sci. 2020;27: 1064–1073.
  17. Liang Z, Di N, Li L, Yang D. Gut microbiota plays a role in the development of polycystic ovary syndrome and its metabolic disorders. Fertil Steril. 2018;110: e124–e125.
  18. Chu W, Han Q, Xu J, Wang J, Sun Y, Li W, et al. Metagenomic analysis identified microbiome alterations and pathological association between intestinal microbiota and polycystic ovary syndrome. Fertil Steril. 2020;113: 1286–1298.e4.
  19. Guo Y, Qi Y, Yang X, Zhao L, Wen S, Liu Y, et al. Association between Polycystic Ovary Syndrome and Gut Microbiota. PLoS One. 2016;11: e0153196.
  20. Knezevic J, Starchl C, Tmava Berisha A, Amrein K. Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function? Nutrients. 2020;12. doi:10.3390/nu12061769
  21. Wu J, Zhuo Y, Liu Y, Chen Y, Ning Y, Yao J. Association between Premature Ovarian Insufficiency and Gut Microbiota. 2020 [cited 4 Jun 2021]. doi:10.21203/rs.3.rs-54121/v1
  22. Zhao S, Pang Y, Zhao X, Du W, Hao H, Zhu H. Detrimental effects of lipopolysaccharides on maturation of bovine oocytes. Asian-australas J Anim Sci. 2019;32: 1112–1121.
  23. Lin L-T, Tsui K-H. The Relationships Between Serum DHEA-S and AMH Levels in Infertile Women: A Retrospective Cross-Sectional Study. J Clin Med Res. 2021;10. doi:10.3390/jcm10061211
  24. Wang L-Y, Wang D-H, Zou X-Y, Xu C-M. Mitochondrial functions on oocytes and preimplantation embryos. J Zhejiang Univ Sci B. 2009;10: 483–492.
  25. Kong Y, Liu Z, Shang Q, Gao Y, Li X, Zheng C, et al. The Disordered Vaginal Microbiota Is a Potential Indicator for a Higher Failure of in vitro Fertilization. Front Med. 2020;7: 217.