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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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