Identification of Distinct Stool Metabolites in Women With Endometriosis for Non-Invasive Diagnosis and Potential for Microbiota-Based Therapies

Authors

• Chandni Talwar
• Goutham Venkata Naga Davuluri
• Abu Hena Mostafa Kamal
• Cristian Coarfa
• Sang Jun Han
• Surabi Veeraragavan
• Krishna Parsawar
• Nagireddy Putluri
• Kristi Hoffman
• Patricia Jimenez
• Scott Biest
• Ramakrishna Kommagani

Language

English

Publication Date

2-14-2025

Journal

Med

DOI

10.1016/j.medj.2024.09.006

PMID

39395412

PMCID

PMC11830556

PubMedCentral® Posted Date

2-14-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Background: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure.

Methods: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in vitro using patient-derived cells and in vivo by employing murine and human xenograft pre-clinical disease models.

Findings: We discovered a unique bacteria-derived metabolite signature intricately linked to endometriosis. The altered fecal metabolite profile exhibits a strong correlation with that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions. Notably, we validated 4-hydroxyindole, a gut-bacteria-derived metabolite that is lower in stool samples of endometriosis. Extensive in vivo studies found that 4-hydroxyindole suppressed the initiation and progression of endometriosis-associated inflammation and hyperalgesia in heterologous mouse and in pre-clinical models of the disease.

Conclusions: 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. Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis.

Funding: This work was funded by the NIH/NICHD grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society to R.K.

Keywords

Humans, Female, Endometriosis, Feces, Animals, Mice, Gastrointestinal Microbiome, Metabolomics, Metabolome, Indoles, Adult, Fecal Microbiota Transplantation, Disease Models, Animal, Endometriosis, Fecal metabolome, Gut microbiome, Female reproductive health

Published Open-Access

yes

Recommended Citation

Talwar, Chandni; Davuluri, Goutham Venkata Naga; Kamal, Abu Hena Mostafa; et al., "Identification of Distinct Stool Metabolites in Women With Endometriosis for Non-Invasive Diagnosis and Potential for Microbiota-Based Therapies" (2025). Faculty, Staff and Students Publications. 7000.
https://digitalcommons.library.tmc.edu/baylor_docs/7000