Gut Health And Fertility

Microbiota: the microorganisms of a particular site, habitat, or geological period.

Microbiome: the microorganisms in a particular environment (including the body or a part of the body).

Dysbiosis: an imbalance between the types of organism present in a person’s natural microflora.

Prebiotic: a non-digestible food ingredient that promotes the growth of beneficial microorganisms in the intestines. For example, fiber or resistant starch.

Probiotic: live microorganisms that are intended to have health benefits when consumed or applied to the body.

We, humans, are walking microbial hosts. Our microbiota outnumbers our somatic cells by trillions (1). An enriched and balanced diversity of gastrointestinal microbiota is undeniably important. Our gut is responsible for much more than just our digestive health. There are links between the gut and the brain, the immune system and the cardiovascular system, meaning the well-being of our gut and its microbiome can potentially affect many other aspects of our health, including fertility. Dysbiosis may participate in the development several disease conditions, including metabolic disorders such as obesity and diabetes (2). Host-bacterial interaction is also sex-dependent, as studies showed the ability of the microbiota to modulate gonadal sex hormones (3), putting forward the concept that gut microbiota dysbiosis may negatively affect reproductive health.

It is well-known that women of a higher weight are at increased risk of reproductive problems. Overweight and obesity lead to low-grade chronic inflammation and oxidative stress that negatively impact egg quality and endometrial receptivity, as well as have other detrimental effects on health and fertility.

The function and composition of our microbiome are influenced by the food that we eat, as well as other health habits. Excess intake of calories, processed meat, and high levels of sugar and salt, along with little to no fibre, has the potential to affect our gut microbiome negatively. In addition, people with obesity and chronic inflammation have been found to have an imbalance in their gut microbiome in comparison to people without these conditions.

The link between obesogenic diet, gut health and infertility has been shown in a recent study in mice which concluded that a high-fat diet could induce gut microbiome imbalance and ovarian inflammation through changes in gene expression (4)

Host-bacterial interaction is sex and hormone-dependent. Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. A study (3) demonstrated that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity. Transfer of gut microbiota from adult mice males to immature females altered the recipient’s microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production. These effects are dependent on androgen receptor activity. Thus, the commensal microbial community can alter sex hormone levels and regulate autoimmune disease fate in individuals with high genetic risk.

It is already well-known that women with autoimmune diseases have a higher risk of infertility.

Recent studies reported differences in the gut microbiome composition of women with polycystic ovary syndrome (PCOS) as compared with healthy women, raising the important question as to whether microbial imbalance might play a causal role in the pathophysiology of PCOS (5,6).

A recent study, issued in Nature Medicine (7), provides evidence supporting a causal link between gut microbiota dysbiosis in women with PCOS and the appearance of PCOS-associated ovarian and metabolic dysfunctions. The authors found dysbiosis (specifically, a remarkable abundance of a bacteria called B. vulgatus) in the gut microbiota of individuals with PCOS.

To understand the underlying mechanisms by which B. vulgatus contributes to the PCOS pathology, the authors analysed the intestinal immune profile of PCOS patients and mice and found changes in the expression of some molecules that modulate the immune system. Moreover, they treated the mice to reestablish their immune balance, and they could show full recovery of reproductive cycles, ovarian morphology, testosterone levels, and insulin resistance.

The findings of this study inspire several new questions as to the precise nature of the mechanisms underlying the immune therapy mediated recovery of reproductive and metabolic function, which are paramount for the prospective treatments in PCOS.
Along this line, an important finding emerging from the study is that the dysbiosis in the gut is sufficient to drive PCOS-like cardinal defects, including hyperandrogenism.

In conclusion, this study sheds new light on the interplay between gut microbiota and reproductive disorders and suggests that modifying the gut microbiome might be of value for the treatment of PCOS.

Gut microbiome alterations have not only been associated with the polycystic ovarian syndrome. A recent review published in Human Reproduction Update (8) reviews the potential relationship between the microbiome and endometriosis, infertility and chronic pelvic pain.
Although there was no clear consensus on specific microbiota compositions associated with endometriosis, bacterial vaginosis-associated bacteria and Lactobacillus depletion in the cervicovaginal microbiome were associated with endometriosis and infertility in the majority of studies. Furthermore, animal studies support a bidirectional relationship between the gut microbiota and endometriosis onset and progression.

Your diet and daily habits have a crucial impact on your microbiome. So here you have some tips to help the good bugs:

1) Aim to consume enough fibre a day. Fibre is found in whole grains, legumes, vegetables, fruit, nuts and seeds

2) Consume prebiotic foods. Prebiotics are foods that feed our good bacteria and have been shown to result in specific changes in the gut microbiota’s composition and/or activity, conferring a benefit to the person. Many forms of dietary fibre act as prebiotics, such as apples, artichokes, asparagus, bananas, berries, cocoa, chicory, hazelnuts and legumes. Incorporating these fibres in your diet can improve the balance of the gut microbiome.

3) Cook your rice and potatoes beforehand and keep them refrigerated for at least 24 hours before consumption. With the cooling process, the starch becomes resistant to digestion in the small intestine and ferments in the large intestine, nourishing the good bacteria in your bowel.

4) Incorporate probiotic foods in your diet. Probiotic foods, which contain live microorganisms, such as kefir and natural yoghurt, have the potential to populate the gut with beneficial bacteria rebalancing the gut microbiome and promoting diversity.

Probiotics are live bacteria and yeasts, which, when taken and reach our gut alive, have the potential to restore the balance of our gut microbiota by increasing the number of ‘good’ or ‘friendly’ bacteria.

Probiotic supplementation has shown positive effects in some specific microbiome alterations. For example, an altered vaginal microbiome may influence fertility (9). Studies have found that oral probiotic supplementation with two Lactobacillus strains can restore healthy vaginal flora in 82% of women with previous vaginal birth microbiome imbalance.

Even though not all products that claim to be a probiotic may reach the required concentration, neither be alive when they get to the targeted organ/tissue (gut, vagina, etc.). It is also important to consider those different microbiome alterations might require different therapeutic interventions and probiotic supplementation. Therefore, ideally, a specialist should prescribe the supplements to target your specific needs.

Prioritising gut health could positively influence both reproductive and overall health. However, even though this is a matter of growing interest and more data and studies are being published, the precise link between the gut microbiome and fertility remains unclear.
Basing your diet on whole grains, fruit, vegetables, nuts, seeds, and lean protein, favouring unsaturated fats, whilst limiting foods that can promote gut imbalance and inflammation, such as high-fat, high-sugar foods and alcohol is the best route to a healthy gut.

Diet is not the only lifestyle factor that you can modify to improve your gut health. Avoiding toxics (alcohol, tobacco, using self-care products free from endocrine disruptors), doing exercise on a regular basis, respecting your circadian rhythms, having enough good quality sleep, and managing stress also impact your microbiome.

It is also important to consult with a specialist if you suffer digestive symptoms, such as reflux, gas, abdominal distention, heavy digestions, or not regularly going to the bathroom. All those might be signs of a digestive issue that needs to be addressed to receive proper treatment and reestablish your gut health.
This is essential to have better overall health and to improve your chances of success if you are trying to get pregnant naturally or with an assisted reproductive treatment.

Dr Maria Arqué (MD, PhD), Medical Advisor of Redia IVF.

References:
(1) Gill S.R et al. Metagenomic analysis of the human distal gut microbiome.Science. 2006; 312: 1355-1359

(2) Ley R.E. et al. Microbial ecology: human gut microbes associated with obesity.Nature. 2006; 444: 1022-1023

(3) Markle J.G.M.Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013; 339: 1084-1088

(4) Davis JS. Connecting female infertility to obesity, inflammation, and maternal gut dysbiosis [Internet]. Vol. 157, Endocrinology. Endocrine Society; 2016 p. 1725–7.

(5) Lindheim L.Alterations in gut microbiome composition and barrier function are associated with reproductive and metabolic defects in women with polycystic ovary syndrome (PCOS): A pilot study.PLoS ONE. 2017; 12: e0168390

(6) Torres P.J.Gut microbial diversity in women with polycystic ovary syndrome correlates with hyperandrogenism.J. Clin. Endocrinol. Metab. 2018; 103: 1502-1511

(7) Qi X.Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat. Med. 2019; 25: 1225-1233

(8) Mary E Salliss et al. The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain Human Reproduction Update, Volume 28, Issue 1, January-February 2022, Pages 92–131.

(9) Garcia -Velasco et al. What fertility specialists should know about the vaginal microbiome: a review. RBO Online. Volume 35, Issue 1, July 2017, Pages 103-112