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Does Polycystic Ovary Syndrome Start with Your Gut Bacteria?

Polycystic ovary syndrome (PCOS) is a common hormonal disorder affecting 4-10% of menstruating women (1, 2, 3).

At the heart of the syndrome is the abnormally high production of androgens (male sex hormones) by the ovaries.

High androgen production creates a characteristic clustering of symptoms that define PCOS, which include (4):

  • Excess facial and body hair growth
  • New or worsening acne
  • Irregular menstruation or lack of menstruation
  • Anovulation
  • Infertility
  • Development of multiple small fluid-filled cysts on both ovaries

In addition to serious reproductive symptoms, the syndrome is associated with a high risk of developing life-threatening chronic metabolic conditions, including insulin resistance, type 2 diabetes, high blood pressure and cardiovascular disease (3, 4).

Despite nearly a century of research (5), scientists have struggled to understand the mechanisms that lead to PCOS (3, 4).

What causes the ovaries to start making too many androgens?

How are changes in reproductive function linked to chronic diseases like diabetes or cardiovascular disease?

We simply didn’t know.

But the latest research indicates that we might finally be on the brink of identifying at least one of the root causes of PCOS.

It seems so counterintuitive that one can almost understand why it’s taken a hundred years to discover: PCOS might actually start in your gut (4).  

As crazy as that sounds, the evidence that PCOS is caused by poor gut health is fast becoming overwhelming.

Let’s look at what the research shows us, and how it implicates gut health in the development of PCOS.

PCOS AND LOW-GRADE INFLAMMATION

Research now shows that PCOS is consistently coupled with low-grade inflammation (4).

The most recent meta-analysis combining the data from over 30 studies found that women with PCOS have, on average, around double the level of key inflammatory markers in their blood compared to women without PCOS (6).

Why is this so important? Two reasons:

  1. It instantly implicated a role for gut health in PCOS
  2. It explained the link between PCOS and the risk for chronic metabolic diseases.

Around the same time, PCOS was linked to low-grade inflammation, there was a flood of new data coming in linking low-grade inflammation to poor gut health and poor gut health to chronic metabolic diseases (7, 8, 9).

The core concept that came out of the studies examining the connections between inflammation, gut health and metabolic disease is the idea that unhealthy bacteria in the gut can cause “leaky gut”, which then allows the passage of immune-stimulating molecules into the bloodstream (10).

Normally, your gut microbiota and your intestinal wall work together perfectly to form a solid barrier between you and the outside world, letting only tiny nutrient molecules into your blood.

When your gut bacteria become imbalanced, however, the walls of your intestine become “leaky”, allowing big molecules that should be kept out to get into your body. Since they don’t belong in your bloodstream, these molecules activate your immune system, causing chronic, systemic inflammation (4, 10, 11).

This chronic inflammation then leads to metabolic disease by inducing insulin resistance (12, 13). Insulin resistance is a condition where the cells of your body don’t respond to the insulin in your blood (14).

Loss of insulin signaling to your cells sets off a chain reaction that ultimately results in hyperglycemia (too much sugar in your blood), hyperinsulinemia (too much insulin in your blood) and hyperlipidemia (too much fat in your blood) (15, 16). All of these are symptoms of metabolic disease.

So, in one fell swoop, discovering that PCOS involved inflammation provided an explanation for why women with PCOS were more likely to experience insulin resistance, diabetes, high blood pressure and cardiovascular disease and suggested that PCOS might involve gut health.

PCOS, LPS AND AGEs

So what are the molecules that pass into your bloodstream when you have imbalanced gut bacteria and leaky gut?

One of the main offenders is a group of molecules called lipopolysaccharides (LPS). As I’ve mentioned before, LPS are molecules that come from Gram-negative bacteria and they have been strongly implicated in inducing the inflammation associated with leaky gut syndrome. Study after study has shown that elevated LPS can lead to chronic inflammation and the development of a wide variety of chronic diseases, from diabetes and heart disease to autoimmune diseases and cancer (17).

To determine if LPS might also play a role in the inflammation seen in PCOS, researchers compared the blood of women who had been diagnosed with PCOS to that of women who had not.  Consistent with the previous research, the women with PCOS were indeed found to have significantly higher levels of LPS-markers in their bloodstreams (18), suggesting that, as with so many other diseases, a leaky gut and elevated LPS may be involved in the development of PCOS.

Interestingly, while examining the women’s blood, scientists noticed that LPS weren’t the only molecules significantly different between the two groups. The blood of women with PCOS also contained abnormally high levels of a class of compounds called advanced glycation end products (AGEs)  (19, 20).  

AGEs are large, complex molecules made by cross-reactions between sugars and proteins that are formed when plant or animal tissues are heated to high temperatures, such as when deep frying, broiling or roasting food (21, 22). Though naturally found in many foods, AGEs are too large to move easily through a healthy gut wall, and their levels are usually fairly low in the body (19, 20).

Intrigued by finding high levels of these molecules in the blood of women with PCOS, researchers decided to take a closer look at AGEs and their potential effects on the body. Their investigations found that, just like LPS, AGEs were able to activate the immune system and trigger inflammation in the body (11).

But that wasn’t all. AGEs were also shown to be able to promote inflammation a second way; they trigger the production of proinflammatory hormones, like tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), from the cells outside the immune system. Scientists discovered that the cells of some organs in your body have a receptor on their surfaces called RAGE (receptor for advanced glycation end products) that, when bound by AGEs, promote inflammation (11).

And here is where scientists knew they were really on to something with AGEs and PCOS. While exploring how RAGE works in the body, researchers found that this receptor is abnormally concentrated in — you guessed it — the ovaries (23). Activation of RAGE in the ovaries was then shown to induce ovarian inflammation and prevent ovarian cells from responding to female sex hormones, particularly luteinizing hormone (LH), properly (21, 24). Since LH is responsible for allowing follicles to mature and ovulation to occur (25), blocking LH signaling by AGEs could directly cause the anovulation and menstrual irregularities seen in PCOS.  

INFLAMMATION TO ANDROGENS

The final piece of the puzzle linking gut health to PCOS fell into place with the realization that chronic inflammation caused by LPS and AGEs can directly lead to elevated androgen levels in the body (4, 26, 27).

As we discussed above, inflammation leads to hyperinsulinemia. Excess insulin has now been shown to be able to drive the ovaries to produce excess androgens. It appears that a special group of ovarian cells, called theca cells, respond to increased insulin by releasing more and more androgens into the blood (26, 27).

Healing PCOS from the Gut

With the final link between insulin and androgen levels, we now have a comprehensive, logical mechanism to explain how PCOS and all its symptoms develop (4). And, as unexpected as it is, it looks like it all starts with dysbiosis, a leaky gut, and the influx of LPS and AGEs into the bloodstream.

Perhaps the most exciting aspect of discovering the causative role of poor gut health in PCOS is the possibility of improving gut health as a potential cure!  

Since this theory is so new, there hasn’t been a ton of research examining the possibility of treating PCOS by balancing the microbiome. But the results of few that have been done suggest that the strategy is promising.

For example, one study placed 23 women with PCOS on a diet containing various amounts of AGEs. The researchers were able to demonstrate that a decreased intake of AGEs leads to lower levels of AGEs, insulin, inflammatory markers and testosterone in the women’s blood (28).

Another study looked at more directly dysbiosis and PCOS. Here, the researchers conducted a double-blind placebo-controlled study with 40 women diagnosed with PCOS. Half the women were given probiotics of healthy gut bacteria that can help heal dysbiosis, while the other half received a placebo. After 2 months, the women taking the probiotics had lower insulin levels than the women taking the placebo (29).

Together, these studies suggest that improving the health of your gut to decrease LPS and AGE absorption may prove a simple and effective way to minimize your symptoms or potentially even cure your PCOS.

So, what steps can you take if you want to improve your gut health and decrease your absorption of AGEs and LPS?

Some useful dietary and lifestyle changes you may consider implementing include:

  • Avoiding AGE-rich foods, such as roasted peanuts, fried or roasted meats or canned foods that have been sterilized by high heat (30).
  • Eating a diet low in refined sugars and fats, as both of sugar and fat can induce dysbiosis and a leaky gut (31, 32); as I discussed in a previous article, the type of fat makes a difference, but I’d still recommend a moderate fat intake for those with metabolic issues and PCOS.
  • Eating a diet rich in fiber; fiber can help prevent or reverse dysbiosis (33) and prebiotic intake can also decrease LPS levels in the blood (34).
  • Exercising regularly, which has been shown to promote the growth of healthy bacteria in your gut (35).
  • Taking a probiotic to help keep your bacterial balance healthy (29, 36).

While these diet and lifestyle changes are a great start to addressing your gut health and associated PCOS, it may also be a good idea to see a practitioner about more in-depth and personalized ways to help you deal with this condition.

Having PCOS is a good sign that you likely have significant dysbiosis. A practitioner would be able to test your microbiota and determine how you should best deal with your microbial imbalance.

If you’d like to dive right into a more comprehensive, systematic approach to addressing microbial imbalances like SIBO or dysbiosis (including testing), check out my 2-month online course Build Your Biome.

If you have PCOS, does this information change how you think about this condition? Let me know in the comments below!

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The Role of Gut Bacteria in Fertility and Estrogen Dominance

I’ve talked before about the importance of optimizing your gut health before getting pregnant in order to promote a healthy pregnancy for both you and your baby.

But what about getting pregnant in the first place… Can your gut bacteria play a role in your hormone balance and fertility?

The science suggests that it very well might!

To understand why let’s take a closer look at infertility and one of its common causes: estrogen imbalance.

INFERTILITY & ESTROGEN DOMINANCE

When you hear the term “infertility,” you likely think of a person or a couple that cannot and will never be able to have children. In the medical world, however, infertility does not refer to a permanent state at all.

A diagnosis of infertility simply means that you have not been able to get pregnant after a year of normal, unprotected sex (1).

It’s actually a diagnosis that is far more common than you might realize. According to recent statistics, between 7% and 15.5% of American women experience infertility in any given year, and the majority of women (51.8%) meet the criteria for infertility at least once during their menstruating years (2).

While there are many reasons a couple might have difficulty getting pregnant, among the most common are hormone imbalances (3, 4). And abnormally high levels of one specific sex hormone is frequently implicated in infertility in both men and women: estrogen (5, 6, 7, 8).

Let’s look at each of these individually.

ELEVATED ESTROGEN AND FEMALE INFERTILITY

Most women need little reminder that our fertility depends on a highly-coordinated 28ish-day cycle in our hormone levels. Most of us also know that one of the key players in this hormonal dance is estrogen.

Estrogen has two very important jobs in the female menstrual cycle. First, it triggers a spike in the levels of a hormone called luteinizing hormone (LH) from the pituitary gland in the brain. This spike in LH levels is what triggers the ovary to release a mature egg into the fallopian tube, where it can be fertilized (9).

After a successful ovulation, though, estrogen works together with yet another hormone called progesterone to prevent a second ovulation from occurring. Estrogen and progesterone do this by acting on the pituitary gland in the brain to make sure no more LH is made until the following cycle (or, if pregnancy occurred, until after birth). At the beginning of the next cycle (menstruation), estrogen and progesterone levels dip down, signaling to the brain that it is safe to produce another spike of LH (9).  

Constant high levels of estrogen, without a significant dip signaling the start of a new cycle, can trick your brain into thinking you’ve already ovulated, and prevent you from ovulating again (9). This is actually the logic behind hormonal birth control (the pill).

As you might imagine, this can play a significant role in infertility.

ELEVATED ESTROGEN AND MALE INFERTILITY

While we often think of estrogen as a female hormone, men also have healthy baseline levels of estrogen that are required for sexual and reproductive functions.

At moderate levels, estrogen promotes (and is necessary for) a healthy libido and the production of sperm in men. At elevated levels, however, estrogen can have the opposite effects (6).

Too much estrogen in men decreases their libido. This is because, as in women, estrogen in men acts on the pituitary gland in the brain to decrease the production of LH. In men, this hormone stimulates the testes to produce testosterone. Without enough LH, there is a drop in testosterone, and low testosterone lowers male libido (6).

Elevated levels of estrogen also decrease the production of sperm by the testes. This is due to the estrogen-induced decrease in LH and testosterone levels, both of which directly stimulate the testes to produce mature sperm (6).

ESTROGEN & YOUR GUT BACTERIA

Clearly, a buildup of estrogen is not optimal for you, or your partner’s, fertility. But what’s any of this have to do with your gut bacteria?

A lot, believe it or not! There are multiple mechanisms which link your gut bacteria to your estrogen levels.

GUT BACTERIA AND ESTROGEN REABSORPTION

Your gut bacteria are actually an integral part of the normal regulation mechanisms your body uses to keep estrogen levels normal.   

See, every day your liver pulls estrogen out of your blood and binds it to a sugar-metabolite called glucuronic acid. This sugar-estrogen complex is then mixed with your bile, which is dumped into your digestive tract to help with digestion (10, 11, 12).

Now, this sugar-estrogen complex is bigger than estrogen by itself and it can’t be absorbed through the intestinal wall very well. Because of this, much of the estrogen gets stuck in the intestines and is eliminated from your body via bowel movements (10, 11, 12).

And this is where your gut bacteria come in. They have special enzymes that are able to cut estrogen free from the sugar, called β-glucuronidases. The freed estrogen molecule can then be easily absorbed and re-enter your bloodstream (10, 11, 12).

This is a natural part of the process and the liver binds more estrogen to bile acids than needed with the knowledge that some of it will be coming back, thanks to your gut bacteria.

This balance can be upset, however, if you have abnormal numbers, types or ratios of bacteria in your intestines (called dysbiosis) (13).

This is because some gut bacteria have β-glucuronidases that free estrogen better than others (14). With an unhealthy mix of gut bacteria, your microbiota can free too much estrogen, allowing much greater levels of estrogen to be reabsorbed back into your body than normal and pushing estrogen levels in your blood up (13).

GUT BACTERIA AND ESTROGEN FROM FOOD

In addition to the role the gut microbiota play in balancing the levels of estrogen you make yourself (called endogenous estrogen), they also regulate how much estrogen and estrogen metabolites you absorb from food sources (called exogenous estrogen).

Some gut microbes have enzymes that enable them to breakdown phytoestrogens (from plants) and polycyclic aromatic hydrocarbons (from barbequed or fried meats) into estrogens (15, 16). These estrogens can then be absorbed through the intestinal wall, raising your blood levels.

In fact, studies show that in men and postmenopausal women, the number one source of estrogen for their whole bodies is intestinal absorption from their food (17). And dysbiosis is associated with higher levels of estrogen in these populations, presumably at least partially through increasing the breakdown of dietary molecules such as phytoestrogens and polycyclic aromatic hydrocarbons (13).

INDIRECT WAYS GUT BACTERIA AFFECT ESTROGEN LEVELS

In addition to the direct ways dysbiosis links your gut health to higher estrogen levels, there are also several indirect links.

For example, an abnormal balance of gut bacteria has been strongly linked to constipation (18, 19), inflammation (20) and obesity (21), all of which may be able to further drive up estrogen levels in your blood (8, 22, 23).

IMPROVING YOUR ESTROGEN BALANCE WITH BETTER GUT HEALTH

So, what does this mean for you if you are planning to get pregnant? What can you do to optimize your estrogen levels and boost your fertility?

Research shows that one of the most beneficial things you can do to optimize your estrogen levels is increase your fiber intake.

A high fiber diet is associated with improved microbial health and decreased risk of dysbiosis (24). In fact, increasing the amount of fiber in your diet for just 2 weeks is enough to significantly improve the composition of your gut bacteria (25).  

Additionally, fiber may be able to directly bind the estrogen-sugar complex in the digestive tract, helping eliminate it from the body. In a study examining estrogen (re)absorption in women, there was a direct and significant relationship between a woman’s fiber intake, the size of her stool, and the amount of estrogen she was able to flush from her body (26).

How you choose to increase your fiber intake is up to you, but boosting your fiber intake by increasing the amount of fiber-rich foods in your diet, rather than through adding fiber supplements, may give you more bang for your buck.

This is because the dietary source of fiber — plants — are also rich in polyphenols (27, 28, 29). As I outline here, polyphenols can help boost the health of your gut bacteria, so plant-based fiber-rich foods treat your dysbiosis to a one-two punch.

While fiber (and fiber-polyphenol-rich plants) is the most well established dietary tool to prevent dysbiosis and lower blood estrogen levels, other dietary and lifestyle changes may also be helpful. These include:

  • Exercising regularly (30)
  • Drinking enough water to stay properly hydrated, preventing constipation (31)
  • Taking a probiotic, which contains healthy gut bacteria that can help repopulate your gut with healthy microbes (32)
  • Avoiding broiled, fried and barbequed meats that are likely to contain high levels of polycyclic hydrocarbons (33)

However, if you have a lot of digestive symptoms like constipation, diarrhea, bloating, or gas, you may need help beyond these simple dietary and lifestyle changes.

This is because digestive symptoms can indicate that you have severe dysbiosis, or conditions like SIBO or parasites that need a more in-depth approach, including antimicrobials (or antibiotics) and other supplements.

That said, you can have imbalanced gut bacteria without any symptoms at all, so if you want to maximize your chances of getting pregnant or prevent estrogen dominance, it’s a good idea to test even if you don’t have digestive symptoms.

There are multiple tests to determine the health of your gut microbiota that can give you more precise information regarding your gut health. This can provide you with a roadmap to optimizing your digestive health and, in turn, your fertility.

If testing indicates you have dysbiosis, SIBO, or any other type of imbalanced gut flora, you’ll want to clear out that bad bacteria and balance your biome. If you need more help with that, check out my 8-week online program, Build Your Biome.

For women who have ever struggled with infertility, did you experience that taking care of your gut health through diet and lifestyle changes made a difference in your ability to get pregnant?

For women who are thinking about starting a family in the near future, do you think you will consider your gut health more now, before you start trying? Tell me in the comments below!