Could gut health hold the key to both?

• Endometriosis is a condition where cells similar to the womb lining grow elsewhere in the body, causing inflammation, pain, and scar tissue.
• The condition is difficult to diagnose — on average, people wait almost 9 years from first reporting symptoms for a diagnosis.
• A new study proposes that endometriosis could be diagnosed using a non-invasive stool sample to measure levels of a bacterial metabolite — 4-hydroxyindole — that is significantly lower in people with endometriosis than those without.
• The researchers also showed that 4-hydroxyindole reduced endometriosis initiation and progression in animal models, so suggest that it might be an effective treatment for the condition.

Endometriosis is a condition that causes severe symptoms in up to 11% of women of reproductive age. It occurs when cells similar to endometrial tissue that lines the uterus grow elsewhere in the body.

The tissue most commonly grows within the pelvic area, but can be found in the gastrointestinal tract, lungs, elsewhere in the abdomen and even, rarely, the brain. The most common symptom is pain and cramping before and during menstruation as the endometrial lesions respond to hormone changes.

• long-term lower back and pelvic pain
• periods lasting more than 7 days
• heavy menstrual bleeding
• bowel and urinary problems, including pain, diarrhea, constipation, and bloating
• blood in the stool or urine
• nausea and vomiting
• fatigue
• pain during sex
• spotting or bleeding between periods
• difficulty becoming pregnant.

Endometriosis UK reports that, on average, people wait 8 years and 10 months from first reporting symptoms to diagnosis.

Now, a new study suggests that endometriosis could be diagnosed by measuring levels of a bacterial metabolite in a stool sample. People with endometriosis, as well as those with IBD, have lower levels of the metabolite — 4-hydroxyindole (4HI) — than those without the conditions.

The study, which appears in the journal Med, also suggests that 4HI might be effective in preventing and treating endometriosis.

Meltem Özkan Girgin, MD, an OB/GYN specialist at the London Regenerative Institute in the United Kingdom, who was not involved in this study, told Medical News Today that:

“A large portion of women worldwide have never had access to a gynecologist or pelvic scan, leaving many unaware that they are suffering from endometriosis. The development of a simple diagnostic tool, such as a stool test, could have a transformative impact on both women and society by providing an easier means of diagnosis.”

Fecal metabolites can be used to identify the make up of the gut microbiota — microorganisms that live in a person’s gut — and look for variations in its composition.

Studies have found that people with endometriosis have a less diverse gut microbiome than people without the condition.

However, it is unclear whether endometriosis is responsible for the lower diversity or lack of microbiome diversity increases the likelihood of endometriosis.

This small study examined stool samples from 18 women with clinically confirmed endometriosis and 37 controls.

On analyzing the samples, the researchers identified 371 metabolites. Of these, 61 metabolites differed between the two cohorts — 50 were reduced in people with endometriosis, and 11 increased. There were 22 stool metabolites that were distinct in those with the condition.

In further analysis, they found that one particular metabolite, 4HI, was significantly reduced in the stool samples from women with endometriosis. They suggest that this could be due to their altered gut microbiota.

The distinct stool metabolite signature the researchers uncovered in people with endometriosis was similar to signatures found in the gut disorders that fall under the IBD umbrella, namely ulcerative colitis and Crohn’s disease.

G. Thomas Ruiz, MD, a board-certified OB/GYN and lead OB/GYN at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, who was also not involved in the study, commented that:

“The connection to IBD is an interesting one, especially if IBD occurs prior to endometriosis as the authors suggest. Could this lead to early intervention in the treatment of endometriosis prior to the onset of the severe scar tissue which often leads to infertility?”

Girgin, however, emphasized that some of the symptoms of endometriosis can be mistaken for those of gut disorders.

“In the last decade, the understanding of microbiota has greatly advanced, highlighting its role in various human pathologies. Women with endometriosis often experience symptoms similar to those of [gut disorders], including bloating, gas, indigestion and intestinal motility problems,” she told us.

The researchers suggest that, because of the significant differences between stool metabolites in healthy women and those with endometriosis, a non-invasive stool test might be developed for diagnosing endometriosis.

Corresponding author, Ramakrishna Kommagani, PhD, associate professor of pathology at Baylor College of Medicine, told MNT that the test “will be straightforward, as the collected stool samples will be sent to clinical diagnostic centers.”

“We have already developed a method to detect this compound in stool, which will be used at these centers to measure the levels,” he shared. “We don’t have a timeline, but it will take 2–5 years to develop this test and make it available for clinicians to utilize,” he added.

Following the stool findings, the researchers carried out investigations into the effect of administering 4HI in animal models of endometriosis.

They found that administration of 4HI prevented the initiation and progression of both inflammation and pain associated with the condition. They are now carrying out studies to evaluate its safety and efficacy as a potential treatment for endometriosis.

While welcoming the findings, Ruiz sounded a note of caution, saying that: “It is hard to judge the significance of this study as the cohort is relatively small. But this is a good start to identify a diagnostic marker, then ultimately more precise therapeutics.”

“Given the significant delay in diagnosing endometriosis, utilizing non-invasive methods could greatly shorten the diagnostic process. Our findings mark an important step forward and hold significant potential to benefit women with endometriosis. Additionally, we established the role of gut microbiota and its metabolites as central to endometriosis pathogenesis, offering new avenues for combating the disease.”

– Ramakrishna Kommagani, PhD