Microbiome dysbiosis and endometriosis: a systematic scoping review of current literature and knowledge gaps.

study questionWhat is the evidence available concerning gut and reproductive tract microbiomes in patients with endometriosis and what are the methodological approaches employed in microbiome studies on endometriosis? SUMMARY ANSWER: The taxonomic profiles exhibited pronounced heterogeneity within women with and also within women without endometriosis across reviewed studies for all the anatomical districts evaluated. WHAT IS KNOWN ALREADY: Both human and animal studies support differences in the microbiome composition of individuals with and without endometriosis. Endometriosis onset occurs with variable symptoms and manifestations. The microbiome composition at different sites may contribute to this variability. STUDY DESIGN SIZE DURATION: We used the scoping review methodology. Systematic searches of studies from the PubMed, EMBASE, and Web of Science databases published between 1 January 2016 and 1 November 2024 addressing endometriosis microbiome characterization in: (i) gut, (ii) vaginal fluid, (iii) cervical fluid, (iv) peritoneal fluid, (v) uterine fluid, (vi) ovarian cyst fluid, (vii) oropharyngeal fluid, and (viii) eutopic and (ix) ectopic tissues were performed using a combination of MeSH terms. References from relevant publications were systematically screened. PARTICIPANTS/MATERIALS SETTING

methodsResults were reported in accordance with the PRISMA-ScR guidelines. Studies that did not report original data, not written in English or providing a review of the field were excluded. From the 2182 publications retrieved, 36 papers were selected and analyzed, focusing on sample characterization (patients, controls, tissues, and fluids) and methodologies used. MAIN RESULTS AND THE ROLE OF CHANCE: Sound evidence is lacking to support a specific gut dysbiosis profile in women with endometriosis. The largest metagenome study performed using shotgun sequencing and controlling for multiple hypotheses testing did not detect significant differences between women with and without the disease. For eutopic and ectopic tissue microbiomes, the literature is too scant to draw any conclusion. Some data suggest a possible enrichment of LIMITATIONS REASONS FOR CAUTION: The number of participants per study greatly varied and, with few exceptions, was typically low. Incomplete information on methodological approaches was broadly observed. The impact of participants' menstrual cycle phase, diet, and drug assumption was frequently not considered. WIDER IMPLICATIONS OF THE

findingsStandardization of research protocols to allow reproducibility is required, as well as collaborations to harmonize data analysis, interpretation, and, more importantly, health outcome prediction or improvement. STUDY FUNDING/COMPETING INTERESTS: The review was funded by the Italian Ministry of Health: RF-2019-12369460, and Current Research IRCCS. P.Vi. serves as co-editor in Chief of Journal of Endometriosis and Uterine Disorders. E.S. serves as Editor in Chief of Human Reproduction Open and discloses research grants from Ferring, Ibsa, Gedeon Richter, and Theramex, and honoraria from Ibsa and Gedeon Richter. P.Ve. serves as Associate Editor for Human Reproduction Open; is a member of the Editorial Board of the Journal of Obstetrics and Gynaecology Canada, of the Italian Journal of Obstetrics and Gynaecology, and of the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynecological practice. All other authors declare they have no conflict of interest. REGISTRATION NUMBER: 10.17605/OSF.IO/X6HBT at https://osf.io/registries.