Are gut health and fertility connected?

The particular composition of your gut microbiome, made up of the trillions of microorganisms (also called microbes) living in your gut, affects your health from head to toe. Scientists have known for quite some time that an unhealthy gut can lead to gastrointestinal (GI) disorders, such as irritable bowel disease (IBD). In recent years, research has also connected gut functioning to a wide variety of other disorders: obesity, diabetes, cardiovascular diseases, certain cancers, and even some neurological disorders. Less studied, but now on the rise, is the connection between gut health and fertility (and a broad range of other reproductive disorders).

In fact, this research has extended beyond the gut microbiome to other, smaller, but still vitally important microbiomes: the uterine and vaginal microbiomes. While new findings are emerging daily, and much more work is needed to determine mechanisms and the relative merits of various therapeutic interventions, it is becoming increasingly clear that dietary and other lifestyle strategies could improve the overall health of all three of these microbiomes, promising to help reduce the incidence of infertility.  

What is infertility?

The World Health Organization defines infertility as a disease of the reproductive system characterized by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. This disorder affects 48.5 million couples worldwide, with important psychological implications for the couples and related negative impacts on the quality of their lives.

What causes infertility

• In the male reproductive system, infertility is most commonly caused by problems in the ejection of semen, absence or low levels of sperm, or abnormal shape (morphology) and movement (motility) of the sperm. It has been estimated that the male partner accounts for the infertility 40% of the time.
  
• In the female reproductive system, infertility may be caused by a range of abnormalities of the ovaries, uterus, fallopian tubes, and the endocrine system, among others. It has been estimated that 40% of the time, it is one of these abnormalities in the female that is causing the infertility.
  
• Approximately 20% of infertility cases involve abnormalities in both the man and the woman.
  
• Infertility can be primary or secondary. Primary infertility is when a pregnancy has never been achieved by a person, and secondary infertility is when at least one prior pregnancy has been achieved.

However, “causation” for infertility is a lot more complicated, and inexact, than the above, simple description and bulk data indicates. The factors behind many of the abnormalities are often a complex blend of congenital, hormonal, morphological and immunological issues. Furthermore, a significant percentage of couples never find out why they can’t conceive; this is called unexplained infertility (UI).

What is unexplained infertility?

Leading sources estimate that unexplained infertility (UI) accounts for as much as 30% of infertility cases. Add to that another disturbing fact: the diagnosis of UI is subjective and often misdiagnosed for endometriosis, tubal infertility, premature ovarian aging and immune infertility. 

As our report will discuss, microbiome health, including gut health, probably impacts most cases of infertility, whether the direct cause of the infertility has been identified or not. In fact, certain researchers believe our best hope of addressing infertility, and in particular the large UI incidence, is by better understanding gut and microbiome health, its complex relationship with reproductive functioning, and how both can be mutually enhanced.

Risks for infertility

The list of factors that can increase an individual’s risk for infertility also provides a window into the “causes behind the causes” of this disorder. Certain infertility risk factors (such as age) are quite general, while other risk factors are more akin to direct causes. Just looking at females, Cleveland Clinic lists these infertility risk factors:

• Age
• Hormone issue that prevents ovulation
• Abnormal menstrual cycle
• Obesity
• Being underweight
• Having a low body-fat content from extreme exercise
• Endometriosis
• Structural problems (problems with the fallopian tubes, uterus or ovaries)
• Uterine fibroids
• Cysts
• Tumors
• Autoimmune disorders (lupus, rheumatoid arthritis, Hashimoto’s disease, thyroid gland conditions)
• Sexually transmitted infections (STIs)
• Polycystic Ovary Syndrome (PCOS)
• Primary Ovarian Insufficiency (POI)
• Excessive substance use (heavy drinking)
• Smoking
• DES syndrome (DES is a medication that was given to women to prevent complications in pregnancy like premature birth or miscarriage. However, this medication has caused infertility in some of the children of mothers who took DES.)
• A past ectopic (tubal) pregnancy

What’s not on this list? An unhealthy gut. But what we’ll learn in the next section is that gut health — or more broadly speaking, microbiome health — is increasingly being considered a risk factor for infertility and a whole host of other reproductive disorders.

Gut microbiome health

As we mentioned at the outset, your microbiota — consisting of millions of bacteria, viruses, fungi, and yeast — play a multitude of roles that affect your health, including extracting nutrients and energy from food, influencing how well your immune system works, and protecting you against bad bacteria, viruses and more. Most, but not all, of such microbiota reside in your gut.

Generally speaking, medical providers define “gut health” as the absence of characteristics such as gastrointestinal (GI) symptoms (e.g., diarrhea and bloating) and disease (e.g., diabetes and IBD). However, scientific researchers increasingly recognize that a gut, even absent outward symptoms of discomfort or disease, could contain abnormal flora that might result in colonization of pathogenic bacteria that eventually lead to a wide variety of other disorders. “Dysbiosis” refers to the imbalance of harmful microbes and has been linked to cancer and other diseases.

Gut health and fertility 

Scores of recent research papers suggest a potential connection between certain gut bacteria and female reproductive tract disorders, such as bacterial vaginosis (BV), cervical and endometrial cancer, polycystic ovary syndrome (PCOS), postmenopausal syndrome, endometriosis, endometritis, and uterine fibroids (UFs). Furthermore, emerging evidence indicates that the composition of the gut microbiome affects fertility — both in females and in males, in part by modulating circulating concentrations of sex hormones such as estrogens, testosterone, progesterone, and corticosteroids. An imbalance in male gut microbiota that leads to dysbiosis has been associated with reduced testosterone concentrations and the increased inflammation and oxidative stress seen in male factor infertility.

The functioning of the gut is so intertwined with the reproductive organs that one 2021 review author called the gut a full-fledged endocrine organ because its microbiota has various effects on the intestinal milieu that influence distant organs and pathways, including the reproductive endocrine system throughout a woman’s lifetime — interacting not only with sex hormones, but also with insulin and other hormones.

Beyond the gut: vaginal and uterine microbiomes

It’s not just the gut’s microbiota that are involved in fertility. Thanks in part to work started in the U.S. in 2007 on “The Human Microbiome Project” (not to be confused with the 2001 publication of the human genome sequence, known as The Human Genome Project), scientists now appreciate that the female reproductive tract (comprising the vulva, vagina, cervix, endometrium, fallopian tubes, and ovaries) harbors its own, unique microbiome that accounts for approximately 9% of the body’s total microbial population. Accordingly, it’s not just “gut health” we should be talking about — but, rather, “microbiome health.” 

While much research has been done on the gut microbiome generally, investigation into its direct and indirect impacts upon the two female reproductive tract microbiomes is in its relative infancy. Work on describing the vaginal microbiota is well underway, but the uterine microbiota is virtually underexplored to date; this fact is illustrated well by remembering that just a decade ago, the uterus, fallopian tubes, and ovaries were thought to be “a sterile niche” — instead of what it’s now considered: a microbiome — i.e,. a breeding ground of microorganisms.

What’s an unhealthy microbiome? 

The science behind why and how one (or all) of these microbiomes becomes unhealthy is complex, and many of the mechanisms involved are not yet well understood. 

Dysbiosis

We know from data on women with recurrent pregnancy loss (i.e., miscarriages), of which 30% have no known cause, that these women have a higher prevalence of undiagnosed gut disorders, especially abnormal gut permeability. As a 2021 review paper noted, “imbalances in the gut microbiota composition” can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer. This imbalance of harmful microbes is known as dysbiosis, which is characterized by “lower microbial diversity” in the gut that impairs the gut’s job of regulating estrogens (through secretion of β-glucuronidase, an enzyme). That impairment then results in a reduction of circulating estrogens, which may contribute to reproductive disorders (such as endometrial hyperplasia, endometriosis, polycystic ovary syndrome — and infertility) as well as to obesity, metabolic syndrome, cancer, cardiovascular disease (CVD) and cognitive function. 

Further complicating the processes, this relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease has been found to be bi-directional.

Chronic inflammation

At the risk of oversimplifying the science, essentially what scientists are determining is that dysbiosis, especially in the gut microbiome, contributes to inflammatory reactions in the body. While acute inflammation is typically normal (i.e., a healthy response to short-term stress or injury), chronic low-grade inflammation — associated with an unhealthy gut — promotes a wide range of disorders and disease states, including infertility. 

Chronic inflammation can damage the lining of your gut and/or lead to elevated levels of inflammation in your circulation, causing damage in other microbiomes (e.g., in the vagina, to developing eggs and sperm). Dysbiosis-induced chronic inflammation also disturbs your entire immune system, a phenomenon known as iso-immunization. One researcher categorizes those cases of infertility that relate to iso-immunization as immune fertility, or “the failure of natural tolerance leading to local and/or systemic immune response…[that] may induce high levels of anti-seminal/sperm antibodies.”

Reproductive dysbiosis and inflammation

A clinical review paper published in late 2022 canvassed recent studies of the gut, vaginal, and uterine microbiomes and summarized the patterns in bacterial composition that have been identified and how they change across individuals’ lives. The authors describe what microbiota quantities look like in healthy and diseased states, and what different patterns appear within the upper reproductive tract (fallopian tubes, ovaries, and uterus, including the endocervix) and the lower tract (the ectocervix and vagina). Even within these microbiomes, there are “microbiomes within microbiomes” [our phrasing], such as the “endometrial microbiome,” which plays a critical role in the reproductive process in premenopausal women. 

While there are too many types of microbiota, patterns (healthy and unhealthy), and interconnections to detail in this report, here are a few of the interesting findings that have been investigated by researchers:

• A 2020 review paper describes how, in particular, Lactobacilli have been reported as the most represented bacteria in the vaginal microbiome, along with Prevotella, Bifidobacterium, Gardnerella, Atopobium, Megasphaera, Sneathia, and Anaerococcus. These bacteria have been implicated in different phases of reproduction from gamete formation, fertilization, pregnancy establishment and maintenance, and in the microbial colonization of the fetus and/or of the newborn. 

• This same review also highlighted studies that have reported a positive correlation between the presence of specific bacteria in the uterus and the onset of pelvic inflammatory disease, an inflammation of the upper genital tract that can lead to infertility. 

• Other studies have investigated bacteria specifically associated with endometriosis. Interestingly, a 2017 paper found that the reproductive tract microbiome of women affected by endometriosis was different from that of women with infertility due to other causes. If confirmed in other studies, this suggests that microbiota-specific alterations may lead to a better stratification of infertile women, and also to the development of different therapeutic strategies.
  
  
• A 2021 review of 28 human and 6 animal studies concluded that “bacterial vaginosis-associated bacteria and Lactobacillus depletion in the cervicovaginal microbiome were associated with endometriosis and [our emphasis] infertility in the majority (23/28) of studies.” Their view of the wider implication:

There is evidence that a dysbiotic gut or genital microbiota is associated with multiple gynecologic conditions, with mounting data supporting an association between the microbiome and endometriosis and infertility. These microbiomes likely play a role in the gut-brain axis, which further supports a putative association with the spectrum of symptoms associated with endometriosis, including infertility and CPP.

How to prevent infertility

While medical provider groups are wise in cautioning that most forms of infertility cannot be predicted or prevented, the risk factors that may contribute to infertility can, in some cases, be controlled to help prevent this condition. For example, lifestyle modifications, such as reducing alcohol consumption and quitting smoking, may be beneficial to one’s fertility, as is maintaining a healthy weight and developing good exercise habits. And, as we’ll discuss below, modifying your diet can have a significant impact on your fertility, a field that scientists are eagerly exploring.

Environmental factors are also under investigation, including the impact of pesticides and other endocrine disruptors, which seem to exert a profound impact on reproductive health. 

Certain physiological conditions that represent infertility risk factors might be mitigated by pharmacological interventions, which is clearly not within the confines of this report to detail. If you are considering starting a family, by all means have that discussion with your medical provider, early, to discuss and evaluate any risk factors you may have, and what can be done to mitigate them.

Lowering your risk of infertility: The focus upon gut health

In light of the growing body of evidence connecting an unhealthy gut to reproductive disorders, including infertility, scientists and physicians are trying to evaluate the ways in which individuals might be able to improve their gut health generally and in ways specific to helping reduce infertility risk. 

Step #1: Diagnose an unhealthy gut, and assess your overall health

Especially if you have outward symptoms of a gut imbalance or disorder, such as severe and continual constipation or prolonged diarrhea, determining the type and extent of the problem is an important first step to knowing how best to improve the health of your gut and to lower risks of complications (such as infertility) that can ensue. Talk with you medical provider, who may order one or more of the following tests:

• Comprehensive stool analysis
• Food sensitivity testing
• Screening for celiac disease
• Different physical tests can be used to search for abnormalities in the gut. These include a colonoscopy, a CT scan, or an upper endoscopy.

Regarding this third test, for celiac disease (CD), the importance of making this diagnosis is especially pertinent to fertility, as undiagnosed celiac disease (CD) has a well-documented, potentially negative impact on female reproduction due to gynecological and obstetric disorders (e.g., delayed menarche, early menopause, amenorrhea) and/or adverse pregnancy outcomes (e.g., recurrent pregnancy loss, intrauterine growth restriction, low birth weight, and preterm deliveries). A 2016 meta-analysis determined that women with infertility had 3.5 times higher odds of having CD; similarly, women with unexplained infertility had 6 times higher odds of having CD. And yet, up until the time of that publication, the data on association between CD and infertility was considered contradictory, and there were no recommendations for the screening of female patients with infertility for CD.

Step #2: Treat your gut 

Treating an unhealthy gut involves a wide range of therapies, depending on the type of gut disorder(s) that a physician might be able to pinpoint. However, we’re not in the business of dispensing medical advice. 

On the other hand, working to maintain a healthy gut is in everyone’s best interest, and seems particularly pertinent to fertility. As mentioned previously, a list of lifestyle modifications can benefit the gut, and also reproductive health — including lower alcohol and caffeine consumption, and curtailment of smoking. 

What is the gut health/fertility lifestyle factor receiving the most attention in scientific circles?: Diet and nutrition, for reasons we’ll delve into in the next section. 

Step #3: Improve gut health (and fertility) through diet/nutrition

Scientists increasingly believe in the possibility of modulating gut microbiota composition through various approaches, including dietary alterations. Such dietary changes can affect both gut and reproductive health simultaneously.  

However, here’s a big disclaimer, courtesy of a 2022 review paper aptly entitled “Personalized Nutrition in the Management of Female Infertility.”  

Whereas the literature on the correlation between diet and fertility is steadily increasing, and the evidence that a strong link between unhealthy dietary habits and infertility is undeniable, there are no official guidelines on the nutritional management of patients seeking a pregnancy. Likewise, IVF is not routinely combined with a nutritional counseling program. Indeed, no specific dietary patterns for improving reproductive chances have yet been identified.

The authors go on to explain that this diet-evidence-health gap is due in large part to the daunting challenges of nutritional research: (i) conflicting results reported from different studies; (ii) limited sample size; (iii) heterogeneity of populations under study; (iv) different confounding factors interfering with the correlation diet-reproductive outcomes; (v) self-reporting in the methods adopted for dietary assessment, such as food frequency questionnaires (FFQs). Clinical studies tend to use a “one size fits all” principle in analyzing stratified nutrition intervention, an approach mostly intended to limit/avoid deficiencies rather than to improve health. However, every individual has their own genome, proteome, metabolome, microbiome, and exposome, namely the totality of exposure over the lifetime, all of which affects their genetics, epigenetics, immune system, and the way dietary components are absorbed, metabolized, and utilized. Thus, “it is utopian, if not impossible, to determine a dietary pattern that fits all patients in relation to the treatment of infertility or any other disease.”

That being said, we’ve assembled a list of nutrition and dietary recommendations, along with some emerging ones, that have achieved the support of leading medical groups and scientists. These recommendations are aimed at improving gut health generally and fertility specifically:

1. Manage your weight management to reduce BMI and obesity risks: The impact of overweight and obesity on reproduction and fertility is of huge significance, mainly due to endocrine mechanisms that interfere with both ovarian and endometrial functions via altered inflammatory responses. As detailed in the aforementioned 2022 review paper, the most compelling clinical research to date points to adoption of diets akin to the Mediterranean diet, with low saturated fats, limited carbohydrates and high protein levels to maintain or lose weight. For overweight and obese individuals, a similar dietary approach, but also including dietary caloric restriction (CR) without severe nutritional deprivation, has been shown to exert an anti-inflammatory effect. 

2. Up your consumption of PUFAs and MUFAs: Mediterranean diets also tend to be rich in omega-3 polyunsaturated fatty acids (PUFAs), as found in fatty fish (such as salmon), and monounsaturated fatty acids (MUFAs), as found in olive oil — both of which are associated not only with weight management and improved overall health, but also with enhanced fertility.

3. Consume a high-fiber diet: Fiber foods, especially prebiotics — and within that group, especially “microbiota accessible carbohydrates” (or MACs) — have been shown to promote gut diversity, resulting in increased quantities of short-chain fatty acids (SFCAs), metabolites which play a vital role in the maintenance of gut, metabolic, cardiovascular, immune, and cognitive health. Butyrate is a SFCA of keen interest for its association with fertility, as it seems to dampen processes that compromise egg and sperm quality and the progression of a healthy pregnancy.

4. Consume adequate amounts of B vitamins and choline: The water-soluble B vitamins, folic acid and folate, are also known as vitamin B9. The two terms are often used interchangeably, although the first refers to the synthetic molecule introduced in supplements or fortified foods, while the second is the form naturally present in some foods, including green and leafy vegetables, sprouts, some fruits, legumes, seeds, and offal. Folates are essential for the synthesis of DNA and proteins, and they have been studied extensively for their role in early embryonic development and other reproductive processes. Furthermore, folate deficiency is directly related to increased levels of inflammatory markers such as IL-β, IL-6, and TNF-α. A correct intake of folate also reduces the risk of obesity in genetically predisposed individuals, as well as reduces the risk of altered glucose metabolism and hypertension. Therefore, adequate amounts of B vitamins, mainly from foods rich in folate and vitamin B12, are essential. 

Choline, sometimes referred to as vitamin J, is an amine that acts as a coenzyme in numerous metabolic reactions, and it is involved in the formation of cell membranes and other important processes related to reproduction. Natural dietary sources of choline are in both water-soluble and lipid-soluble forms, with high concentrations in milk, liver, egg yolk, meat, and wheat germ. 

5. Get enough vitamin D: This important micronutrient has been shown to aid in the prevention and treatment of uterine fibroids leading to infertility. However, regarding modulation of women’s fertility from other causes, research findings are conflicting, and no clear cause-effect relationship has yet been established. Altered vitamin D concentrations could be a sign of defective intestinal homeostasis, rather than an issue relating directly to fertility. In either case, though, maintaining adequate vitamin D levels is generally recommended — through adequate exposure to sunlight; from consumption of salmon, mushrooms, sardines, eggs; and, when necessary, via supplementation.

6. Manage your blood glucose levels via nutrition (or other means recommended by your medical team): An unbalanced intake of macronutrients such as carbohydrates can promote both inflammation and oxidative stress leading to high blood glucose levels and ultimately to conditions such as obesity, metabolic syndrome, diabetes, leaky gut syndrome, and Alzheimer’s disease. A large body of evidence supports the role of carbohydrates in fertility, as well, leading to the conclusion that “dietary adjustments to reduce insulin secretion represent an intriguing non-pharmacological perspective to counteract infertility.” Appropriate dietary interventions for the management of blood glucose include reduced intake of simple sugars, especially from sweet drinks, sweets, and fruit juice, in favor of complex, low-glycemic-index carbohydrates (e.g., whole grain or ancient grains rich in dietary fiber). 

7. Consume foods high in antioxidants: Increasing evidence suggests that many nutrients and non-nutrient foods and components such as phytochemicals modulate inflammation both acutely and in the long term, and that an adequate intake of certain antioxidants is associated with shorter time to pregnancy. Several foods exert both antioxidant and anti-inflammatory activities, such as whole grains, plant foods, herbs, and spices. Furthermore, both anti-inflammatory and antioxidant properties have been associated with the intake of omega-3 fatty acids, olive oil, garlic, fermented milk, and oilseeds. Some other important bioactive compounds exerting a strong protective antioxidant effect are curcumin and capsaicin. However, research in this area is ongoing.

8. Consume multi-strain probiotics (e.g., Bifidobacterium and Lactobacillus, normally found in fermented foods such as yogurt and kefir): Especially when combined with prebiotics and synbiotics, probiotics can contribute to the healthy composition of the gut microbiota and, thus, improve infertility-related and pregnancy-related disorders.

9. Dairy avoidance?: To reduce the immune-inflammatory response, the leaky gut diet also suggests a diet free of milk and dairy products. However, we put a question-mark here, as research results in this area as it relates to fertility are conflicting, and currently there is no indication to remove all dairy products from the diet of an infertile patient. Part of the discrepancies reported in the literature could depend on lactose digestion and absorption, which are highly variable across individuals. While lactose-intolerant individuals should certainly avoid lactose dairy products, due to the uncomfortable gastrointestinal symptoms that can result, since this is not an allergy, a completely lactose-free diet is not required if symptoms are mild. (Some forms of lactose maldigestion also improve following a targeted use of probiotics such as Lactobacillus spp.)

If the above dietary recommendations seem very similar to ones suggested for reducing your risk of metabolic syndrome, diabetes, obesity and cardiovascular disorders… they are — which is hardly a coincidence. Scientists have discovered that there is a strong relationship between infertility and common chronic noncommunicable diseases (NCDs). Infertile women are, in fact, more subject to premature mortality due to cancer (i.e., digestive organs, genito-urinary organs, and lymphatic and hematopoietic tissue) and non-malignant diseases of the gastrointestinal system. Therefore, nutritional support in infertile patients is even more important due to its potential long-term protective effect.

A note on IVF procedures and gut/microbiome health

Without detailing all of the medical interventions designed to address infertility, clearly IVF techniques, part of a group of “assisted reproductive technologies (ART),” are among the most effective means to treat infertility today. However, despite significant and constant advances in ART, success rates have only marginally increased across the decades.

As a 2020 paper detailed, gut, vaginal and uterine dysbiosis can negatively impact IVF pregnancy rates, suggesting that therapies which attempt to modulate those microbiomes — e.g., increase Lactobacilli and decrease anaerobe microbes — may improve IVF outcomes. The study authors suggest that probiotics may be useful in these patients; indeed, several oral and vaginal probiotics containing Lactobacillus spp. are available on the market. However, the efficacy of these treatments, alone or coupled with antibiotics, is still under investigation. Prescribed antibiotics alone have also been studied, but with controversial results.

Key takeaways

A carefully balanced diet can help you maintain or improve the health of your gut microbiome, with wide-ranging health impacts — including upon fertility and other reproductive functions. Diet is not the only factor involved, but its impact appears significant, even though much more research remains to be done to understand mechanisms, causality, and the relative merits of various nutritional and other therapies. At present, the science is pointing to a diet high in fiber, omega-3 MUFAs and PUFAs, vitamins and minerals (particularly B vitamins and vitamin D), probiotics, and antioxidants; and a diet low in saturated fats and high-glycemic carbohydrates (such as found in processed foods and foods high in added sugars).

It’s not always easy to obtain fresh, whole food sources in all these important categories. Dietary supplements can help, including Eden’s daily synbiotic supplement — a 3-in-1 superblend of prebiotics, probiotics, and polyphenols, formulated to give your good gut microbes everything they need to thrive.