Microbiota and Immunoassay in Women With and Without Endometriosis: a Pilot Study

Endometriosis is an estrogen-dependent chronic inflammatory disease characterized by the presence of endometrial tissue outside the uterine cavity. This pathology has a prevalence of about 5-10% in reproductive-aged women. Endometriosis therapy uses two options: surgical or medical (hormonal) but none can be considered completely resolving. Related signs and symptoms include dysmenorrhea, dyspareunia, infertility, dysuria and dyschezia. In addition to typical gynecological symptoms, gastrointestinal symptoms (bloating, nausea, constipation, diarrhea and vomiting) affect up to 90% of patients with endometriosis. Despite its high prevalence and associated morbidity, its etiology is still unclear and is thought to be multifactorial, and genetic, hormonal, environmental and immunological factors contribute to it. Several studies have shown a significant association between abnormal immune response and maintenance of disease activity in women with endometriosis.

The microbiome contains all the genetic material of microbes, including bacteria, fungi, viruses and Archaea, which live inside the host and regulate various physiological functions. The set of these bacteria, fungi, viruses and Archaea is called a microbiota. The influence of the microbiome on immunomodulation and the development of various inflammatory diseases is well established. Conversely, little is known about the presence and composition of the microbiome in the female reproductive system and its role in the development of endometriosis or other gynecological conditions. Considering the altered inflammatory state typical of endometriosis, it seems logical to postulate a potential role of the microbiome in the etiopathogenesis of this pathology. Interestingly, the microbiome affects estrogen metabolism and estrogen affects the gut microbiome. Since endometriosis is an estrogen-dependent disease, a picture of intestinal dysbiosis resulting in abnormal circulating estrogen levels could potentially contribute to the development of this disease.

Study Overview

• Status: Recruiting
• Conditions: Endometriosis; Endometriosis-related Pain
• Intervention / Treatment: Diagnostic test: Blood, fecal, vaginal and endometrial liquid samples

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura Buggio, MD; Phone Number: 0255032318; Email: laura.buggio@policlinico.mi.it
• Study Contact Backup: Name: Dhouha Dridi, MD; Phone Number: 0255032318; Email: dhouha.dridi@policlinico.mi.it

Study Locations

• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
    • Contact: Laura buggio, MD; Phone Number: +393388720855; Email: laura.buggio@policlinico.mi.it
    • Contact: Dhouha Dridi, MD; Phone Number: +393429370961; Email: dhouha.dridi@policlinico.mi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI <30 kg / m2
• no hormonal therapy (estrogen-progestin, progestogen, GnRH analogues) in progress for at least 1 month
• the endometriosis group include women who will undergo surgery for endometriosis. The control group include women who will undergo surgery for other gynecological indications (i.e .: abdominal surgical emergencies, tubal infertility, non-endometriotic ovarian cysts) in which the presence of endometriosis will be excluded during the surgery.

Exclusion Criteria:

• hormonal therapy in progress (estrogen-progestins, progestins, GnRH analogues)
• antibiotic and / or probiotic therapy in the 8 weeks before the samples
• pregnancy
• menopausal state
• BMI ≥ 30 kg / m2
• presence of active systemic diseases, neoplasms, positive clinical history for autoimmune diseases, active vaginosis or positive history for pelvic inflammatory disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endometriosis group; The endometriosis group will include women who will undergo surgery for endometriosis.	Diagnostic test: Blood, fecal, vaginal and endometrial liquid samples; During the surgical pre-hospitalization, eligible patients who accept participation in the study will undergo a blood sample and collection of stool samples. Before surgery, after anesthesia, they will undergo a vaginal swab and endometrial fluid sampling.
Experimental: Control Group; The control group include women who will undergo surgery for other gynecological diseases in which the presence of endometriosis will be excluded during the operation.	Diagnostic test: Blood, fecal, vaginal and endometrial liquid samples; During the surgical pre-hospitalization, eligible patients who accept participation in the study will undergo a blood sample and collection of stool samples. Before surgery, after anesthesia, they will undergo a vaginal swab and endometrial fluid sampling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal, vaginal and endometrial microbiota in patients with and without endometriosis	The intestinal, vaginal and endometrial microbiota in patients with endometriosis is different than the intestinal, vaginal and endometrial microbiota in patients without endometriosis	8 months
inflammatory, immunophenotype and hormonal status in patients with and without endometriosis	Differences of the inflammatory state, immunophenotype and hormonal status of the two groups of patients.	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular, immunological characteristics of the inflammatory endometriosis environment	the molecular and immunological characteristics of the inflammatory environment of endometriotic lesions and peripheral blood changed from women with and without endometriosis	8 months
Microbiota and sites, symptoms, hormonal treatments of endometriosis	Any differences regarding the composition of the microbiota based on the location of the disease, the presence of symptoms or previous hormonal treatments.	8 months
The impact of the various factors in determining the disease	The relative impact of the various factors in determining the disease combining characteristics of the microbiota with clinical data (genetic, serological, immunological and metabolic).	8 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Investigators: Principal Investigator: Laura Buggio, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): November 30, 2023

Study Registration Dates

• First Submitted: March 9, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Microbiota; Diagnosis; immunoassay
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometriosis
• Other Study ID Numbers: 0009206 u

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No