Specific gut metabolites may help diagnose endometriosis

The findings suggest that 4-hydroxyindole could be a promising biomarker for diagnosing endometriosis.
Table of Contents

What is already known
Endometriosis is a long-term condition that affects up to 198 million women globally and that can lead to infertility. It occurs when tissue similar to the lining of the uterus grows outside of it, causing inflammation and pain. Diagnosing this condition typically involves invasive surgery, and even when lesions are surgically removed, symptoms return in as many as 75% of cases.

What this research adds
Researchers analyzed stool samples from 18 women with endometriosis and found that they have a distinct gut microbiota profile compared to healthy women. Many of the microbial alterations in women with endometriosis mirrored those found in people with inflammatory bowel diseases (IBD), suggesting a possible link between the two conditions. Women with endometriosis also had reduced levels of 4-hydroxyindole — a metabolite produced by gut bacteria such as Faecalibacterium and Bacteroides that is thought to have anti-inflammatory properties. Feeding the metabolite to mice with endometriosis reduced the size and inflammation of lesions.

Conclusions
The findings suggest that 4-hydroxyindole could be a promising biomarker for diagnosing endometriosis. The results also show that endometriosis and IBD share many symptoms, which may explain why endometriosis is often misdiagnosed as IBD.

Endometriosis is a long-term condition that affects up to 198 million women globally and can lead to infertility. Now, researchers have found a surprising link between this condition and the community of microbes living in the gut, identifying microbial metabolites that may help diagnose endometriosis.

The results, published in Med, also show that endometriosis and inflammatory bowel diseases (IBD) share many symptoms, which may explain why endometriosis is often misdiagnosed as IBD.

Endometriosis occurs when tissue similar to the lining of the uterus grows outside of it, causing inflammation and pain. Diagnosing this condition typically involves invasive surgery, and even when lesions are surgically removed, symptoms return in as many as 75% of cases.

Previous studies have shown that certain gut bacteria and their products, such as butyrate, can have protective effects against endometriosis in animal models. But whether specific bacterial metabolites could help diagnose the condition remains unclear.

To address this question, researchers led by Chandni Talwar at Baylor College of Medicine in Houston, Texas, analyzed stool samples from 18 women with endometriosis and 31 healthy women.

Endometriosis biomarker

Women with endometriosis have a distinct gut microbiota profile compared to healthy women. Many of the microbial alterations in women with endometriosis mirrored those found in people with inflammatory bowel diseases (IBD), suggesting a possible link between the two conditions.

In stool samples from women with endometriosis, the researchers identified 22 metabolites produced by gut bacteria that differed from those observed in health women. Of these metabolites, 12 showed diagnostic potential for endometriosis.

For example, women with the condition showed decreased levels of the bacterial metabolite 4-hydroxyindole, which is produced by gut microbes such as Faecalibacterium and Bacteroides and is thought to have anti-inflammatory properties.

Therapeutic target

Further experiments showed that in mice with endometriosis, 4-hydroxyindole reduced the progression, size and inflammation of lesions, as well as associated pain.

The beneficial effects of this metabolite were associated with reduced inflammation and infiltration of immune cells called macrophages. This suggests that 4-hydroxyindole may have a protective role in the disease, the authors say.

“Our findings are the first to provide a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics,” they add. “Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis.”