Endometriosis: The Gut & Vaginal Microbiome as Drivers

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I have been holding off writing an article on endometriosis and bacterial infections for quite some time now. Recently there has been some high level science pointing to what some researchers have suspected for quite some time. The implication that a dysbiotic microbiome – infections and/or overgrowths of microbes that co-inhabit our body – may be one of the drivers of endometriosis. This is big news.

Today we will outline the research connection bacterial infections and endometriosis and describe some tools that can be used to get to the bottom of whether bacterial infections or overgrowths are playing a role in your endometriosis. 

But first let’s cover what endometriosis actually is and some commonly seen symptoms. 

What is Endometriosis Exactly? 

Let me start by saying that there are many unanswered questions surrounding endometriosis. 

There was a recent paper published trying to come to some consensus on the classification of endometriosis. It is considered an inflammatory disease whereby endometrial-like tissue form lesions outside of the uterus. It is multifactorial, with different women presenting with different manifestations of the disease. 

The problem with endometriosis diagnosis is that it is hard. Some leaders in the field consider laparoscopy to be the gold standard for diagnosis. 

‘Some argue that without laparoscopy there can be no diagnosis, thus no classification’

Yup, you read right. Without surgery to assess the pelvic region a proper diagnosis cannot be made.

There are a number of different attempts to try and predict endometriosis in patients using formalised classifications including

  • The revised American Society for Reproductive Medicine (r-ASRM) classification
  • The Enzian classification for deep endometriosis
  • The endometriosis fertility index (EFI)  
  • The American Association of Gynecological Laparoscopists (AAGL) classification  

Imaging (MRI and ultrasound) technology keeps coming up short. A review done in 2016 of 49 different studies, including 4807 patients, concluded that imaging is not quite ready for prime time when it comes to endometriosis diagnosis. The authors noted that imaging can come in handy and does pick up certain forms of endometriosis but that surgery is still the most accurate.

There are a number of different types of endometriosis, characterised by the form it takes. The image below outlines the different forms including deep infiltrating endometriosis (DIE), ovarian endometriotic cyst (EC) also known as endometriomas, or chocolate cysts, and superficial endometriosis.

Image taken from: The Origin and Pathogenesis of Endometriosis

Symptoms of Endometriosis

Endometriosis affects approximately 10% of women at reproductive age. Of those affected by endometriosis up to 50% of them suffer from chronic pelvic pain and/or infertility.  Pain and infertility are the two most common symptoms of endometriosis (3).

Other symptoms may depend on where the endometriosis lesions occur.

In the bladder symptoms may include

  • Painful or difficult urination
  • Blood in the urine

Endometriosis in the ovaries may result in pelvic pain and endometriosis in the vagina may result in pain during or after intercourse and painful periods (4).

Image taken from: Endometriosis: clinical features, MR imaging findings and pathologic correlation

Theories on Root Causes of Endometriosis 

There are a number of risk factors associated with endometriosis including an increased risk in women with Asian ethnicity, excessive oestrogen exposure and a low body mass index (3).

The disease is associated with a whole range of other female reproductive disorders – Are there root cause drivers implicating all of these diseases?

Image taken from: The Origin and Pathogenesis of Endometriosis

But what are the root causes of endometriosis? 

Well the long and short of it is that we still don’t know. Most theories are pretty darn weak. We still have much to learn. That said, there are strong suspicions, backed by at least some scientific evidence which we will cover here. 

Theory on Endometriosis #1. Retrograde Menstruation 

Retrograde menstruation appears to be the best current theory on the development of endometriosis but isn’t without it’s issues.

The retrograde flow of menses transports fragments of cells from the endometrium back through the fallopian tubes and into the peritoneal cavity. Here they implant into tissues and begin to form the characteristic lesions (5).

Theory on Endometriosis #2. Endometrial Stem Cell Recruitment 

This theory on endometriosis involves the recruitment of stem cells from the bone marrow or the endometrium. These cells, in concert with hormones and other factors, leads to the implantation, inflammation and the formation of new blood vessels that support the growth of the lesions (3).  

Theory on Endometriosis #3. Bacterial Contamination 

There is quite a number of studies connecting bacterial infections or overgrowths to endometriosis.

But how can bacterial infections lead to endometriosis

First off it is important to cover lipopolysaccharide. Also known as LPS or endotoxin, this substance is found on the cell walls of gram negative bacteria. It is potently immunogenic – promotes a strong immune response (6).

Image taken from: Lipopolysaccharide modification in Gram-negative bacteria during chronic infection

LPS was found to be 4-6 times higher in the menstrual fluid of patients with endometriosis. When they looked at the peritoneal fluid of endometriosis patients they found that LPS peaked during menstruation (7). 

One study found that LPS was significantly higher in the menstrual fluid and peritoneal fluid of women with endometriosis compared to controls. The authors found that a combination of LPS and estradiol, also found to be elevated in endometriosis patients (but only in the peritoneal fluid this time and not the menstrual fluid) had an additive effect on the endometrial lesions and pelvic inflammation (8).

It is important to note that we will never be completely free from endotoxins. 

They are found in the cell walls of many bacteria that are found in a healthy gut  microbiome. What we are looking to do when we focus on microbiome restoration is to reduce the more pro-inflammatory bacteria and increase the anti-inflammatory members. 

Microbes are Everywhere…even in the uterus!

For awhile now researchers have been exploring the connection between dysbiosis – an imbalance in the microbiota – and endometriosis. 

As we have previously covered, endometriosis is characterised by inflammation as seen by 

  • Elevated levels of immune mediators
  • Reduced T regulatory cells in the periphery and the endometrium 
  • Increased T regulatory cells in the ectopic endometrial tissue

As such, endometriosis is seen as a disease with autoimmune-like and chronic inflammatory patterns (9).

Previously, as with many different organ sites, we thought that both the uterus and the cervix was sterile. 

How wrong we were. Both the cervix and the uterus has its own associated collection of bacteria (10, 11).

Not only were we wrong, but we are now starting to tease out just how important these microbiome sites are for female reproductive health. It can influence rates of preterm birth and neonatal mortality and resistance or susceptibility to sexually transmitted infections (12). 

Connecting Microbes to Endometriosis

As I mentioned at the start of this article, I have been holding off writing about the connection between bacterial infections and overgrowths and endometriosis for some time. While the science provided above has been available for some time, I wanted to read some high level evidence before coming to any conclusions.

A recent systematic review, published in 2019, provided some additional support for the bacterial contamination theory on endometriosis. The review explored the studies connecting different areas of the body, their associated microbial communities and endometriosis.

The review concluded that ‘The microbiome may be involved in the pathogenesis of endometriosis’. Many of the studies found an increase in bacteria found in the Proteobacteria phylum. These bacteria, all gram-negative, are very pro-inflammatory trigger the immune system if they are overrepresented. 

Furthermore, the oestrogen-microbiome connection (or the estrobolome) helps to explain where the excessive oestrogen originates from. 

While a deep dive into the action of beta-glucuronidase enzymes, produced by certain bacteria in the gut, is beyond this article it is worth mentioning in passing. Certain bacteria have the ability to deconjugate oestrogen in the gut, effectively reversing phase 2 detoxification. This action takes oestrogen that has been marked for excretion and allows it to enter back into circulation, thus increasing the load of oestrogen in circulation (14).

The image below helps to explain this process of conjugation, deconjugation by bacteria, enterohepatic circulation and finally circulation of oestrogen. 

Image taken from: The Intestinal Microbiome and Estrogen Receptor–Positive Female Breast Cancer  

Bacterial Infections and Endometriosis. Where to from here?

We are just beginning to get a grip on how relevant the makeup is of these different microbial communities, but certain compositions (proinflammatory bacteria) may be a driver of inflammation and the dysfunctional immune system that is a characteristic of the disease progression.

We need more human studies assessing the bacterial balance in women with endometriosis. 

One interesting study assessed the vaginal pH of women with endometriosis and controls. They found a significant increase in vaginal pH above 4.5 in the women with endometriosis (15).

Assessing the vaginal pH in patients with endometriosis

Assessing the vaginal pH in patients with endometriosis is an easy, affordable and effective way to assess for bacterial infections and overgrowths in the vaginal ecosystem (known as bacterial vaginosis or BV). A vaginal pH above 4.5 is trending away from a healthy ecosystem and towards an imbalanced ecosystem (16).

More on that in an upcoming article. 

Image taken from: Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health

Assessing the gut microbiome in patients with endometriosis

We are still trying to determine which microbiome site is implicated in the progression of endometriosis. In the same systemic review the collection of studies that looked at the bacterial balance in the gut of patients with endometriosis found some evidence of dysbiosis.

With this in mind it may be wise to assess your gut microbiome at the same time. 

With the closure of Ubiome I have been recommending Thryve to many people who are interested in their microbiome composition. 

Image taken from: Thryve

It takes a well educated, gut savvy clinician to interpret microbiome assessments. True, companies providing these tests attempt to provide interpretations and recommendations based on the raw data. These should be interpreted with caution and I would very much recommend working with someone who knows how to balance the microbiome effectively. 

Takeaway Points

To review the takeaway points in this article we can see that endometriosis still has so many unanswered questions. There are a number of different theories that help to explain why endometriosis occurs. Some theories overlap. 

The emerging picture of bacterial infections and overgrowths known as the bacterial contamination theory of endometriosis helps to explain the dysregulated immune system and inflammatory cascade that is present in endometriosis patients. Some recent, high level science, has helped to tie together different areas of the body, their resident microbes and endometriosis. Future studies will help to tease out the details of these different microbiomes and their implications on the progression of endometriosis. 

If you are looking for support in assessing your bacterial balance, screening for microbial infections and wanting to know how to address anything found please book an appointment with us here at Byron Herbalist and we will see if we can help.

Now over to you. Do you have any experience with endometriosis? What has helped you in your healing journey?  

References and Resource

  1. World Endometriosis Society consensus on the classification of endometriosis
  2. Imaging modalities for the non-invasive diagnosis of endometriosis (Review)
  3. The Origin and Pathogenesis of Endometriosis
  4. Endometriosis: clinical features, MR imaging findings and pathologic correlation
  5. Rethinking mechanisms, diagnosis and management of endometriosis
  6. Obesity, inflammation, and the gut microbiota
  7. Bacterial contamination hypothesis: a new concept in endometriosis
  8. 17b-Estradiol and Lipopolysaccharide Additively Promote Pelvic Inflammation and Growth of Endometriosis
  9. Reproductive Microbiomes: Using the Microbiome as a Novel Diagnostic Tool for Endometriosis
  10. The Cervical Microbiome over 7 Years and a Comparison of Methodologies for Its Characterization
  11. Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene
  12. The Cervical Microbiome over 7 Years and a Comparison of Methodologies for Its Characterization
  13. Endometriosis and the microbiome: a systematic review
  14. The Intestinal Microbiome and Estrogen Receptor–Positive Female Breast Cancer 
  15. Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis
  16. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health
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