O-081 Serum metabolic profiling in endometriosis reveals a strong metabolic signature for peritoneal endometriosis

Abstract

Study question What are the metabolome differences between the serum of patients with endometriosis and control subjects? What metabolic traits are characteristic of peritoneal and/or ovarian endometriosis? Summary answer Endometriosis patients have high abundance of riboflavin, tryptophan and purine metabolites in serum. Peritoneal endometriosis has stronger metabolic signature than ovarian endometriosis compared to controls. What is known already Endometriosis patients exhibit different metabolic traits compared to healthy subjects. Several metabolomics studies were conducted on different types of samples (serum, plasma, peritoneal fluid, follicular fluid, eutopic/ectopic endometrial tissue, urine, cervical swabs). However, the sample sizes are limited, and inclusion/exclusion criteria vary. Alterations in amino acid levels, (phospho)lipid metabolites, and purine metabolites are described, though results are controversial depending on sample type and study design. Currently, there is no biomarker for endometriosis and its pathomechanism is still unclear. Study design, size, duration Serum samples were obtained before surgery from 338 dysmenorrheic and/or infertile patients undergoing laparoscopic surgery at a university-affiliated fertility center from February 2019 to October 2024. Patients with hormonal treatment, psychiatric medication, immunosuppressive treatment, hyperthyroidism, autoimmune diseases, hyperprolactinaemia, malignancy, systemic diseases, liver-, kidney diseases, and infection were excluded. Patients were divided into groups based on their laparoscopic diagnosis: peritoneal endometriosis (PE, n = 61), ovarian endometriosis (OE, n = 33), or control group (n = 87). Participants/materials, setting, methods Peritoneal group included ASRM I-II (#Enzian P1-2, O0, T0-2), ovarian group included ASRMI-IV (#Enzian P0-3, O1-2, T0-1) endometriosis stages. Controls had a negative laparoscopic diagnosis for endometriosis. Metabolite profiles were investigated by liquid chromatography (UHPLC-MS) coupled with high-resolution mass spectrometry. Semitargeted and untargeted metabolomics analyses were performed. Semitargeted analysis monitored around 50 metabolites, including vitamins, amino acids, sugar, tryptophan-derivates, and nucleotides. Statistical analyses were conducted to identify metabolic differences between endometriosis patients and controls. Main results and the role of chance Endometriosis groups (PE, OE) have different metabolic profiles compared to symptomatic controls. Interestingly, PE group is well-separated metabolically from both the control and OE groups. OE group shows an intermediate metabolic profile between PE and control groups. Peritoneal endometriosis has a stronger metabolic signature than ovarian endometriosis. Semitargeted analysis revealed significant metabolic alterations in the tryptophan and riboflavin pathways, including kynurenines, indols, and riboflavin intermediates. Limitations, reasons for caution A dietary questionnaire was not conducted among patients. No information is available on the diet of patients, which could alter their metabolic profiles. The #Enzian score was established in 2021; we evaluated it retrospectively for older samples based on the operation reports. Wider implications of the findings A well-described metabolic signature of endometriosis might allow the identification of early biomarkers for endometriosis. It could also give deeper insight into the pathomechanism of the disease. Furthermore, it might provide hypotheses for designing nutritional interventions to prevent progression or reduce postoperative recurrence of endometriosis. Trial registration number Yes