The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain. Salliss Mary E,Farland Leslie V,Mahnert Nichole D,Herbst-Kralovetz Melissa M Human reproduction update BACKGROUND:Endometriosis is a chronic, burdensome condition that is historically understudied. Consequently, there is a lack of understanding of the etiology of the disease and its associated symptoms, including infertility and chronic pelvic pain (CPP). Endometriosis development is influenced by estrogen metabolism and inflammation, which are modulated by several factors including the microbiome and the estrobolome (the collection of genes encoding estrogen-metabolizing enzymes in the gut microbiome). Therefore, there is increasing interest in understanding the role of microbiota in endometriosis etiology. OBJECTIVE AND RATIONALE:To date, there is no cure for endometriosis and treatment options often are ineffective. This manuscript will review the potential relationship between the microbiome and endometriosis, infertility and CPP and highlight the available data on the microbiome in relation to endometriosis and its related symptoms. The overarching goal of this manuscript is to inform future microbiome research that will lead to a deeper understanding of the etiology of the disease and possible diagnostic modalities and treatments. The potential impact of the microbiome on estrogen regulation modulated by the estrobolome, as well as inflammation and other endometriosis-promoting mechanisms within the genital tract, will be reviewed. The methodological limitations of microbiome-related studies will be critically assessed to provide improved guidelines for future microbiome and clinical studies. SEARCH METHODS:PubMed databases were searched using the following keywords: endometriosis AND microbiome, infertility AND microbiome, pelvic pain AND microbiome, IVF (in-vitro fertilization) AND microbiome, endometriosis AND infertility. Clinical and preclinical animal trials that were eligible for review, and related to microbiome and endometriosis, infertility or CPP were included. All available manuscripts were published in 2002-2021. OUTCOMES:In total, 28 clinical and 6 animal studies were included in the review. In both human and animal studies, bacteria were enriched in endometriosis groups, although there was no clear consensus on specific microbiota compositions that were associated with endometriosis, and no studies included infertility or CPP with endometriosis. However, bacterial vaginosis-associated bacteria and Lactobacillus depletion in the cervicovaginal microbiome were associated with endometriosis and infertility in the majority (23/28) of studies. Interpretation of endometrial studies is limited owing to a variety of methodological factors, discussed in this review. In addition, metadata outlining antibiotic usage, age, race/ethnicity, menopausal status and timing of sample collection in relation to diagnosis of endometriosis was not consistently reported. Animal studies (6/6) support a bidirectional relationship between the gut microbiota and endometriosis onset and progression. WIDER IMPLICATIONS:There is evidence that a dysbiotic gut or genital microbiota is associated with multiple gynecologic conditions, with mounting data supporting an association between the microbiome and endometriosis and infertility. These microbiomes likely play a role in the gut-brain axis, which further supports a putative association with the spectrum of symptoms associated with endometriosis, including infertility and CPP. Collectively, this review highlights the demand for more rigorous and transparent methodology and controls, consistency across the field, and inclusion of key demographic and clinical characteristics of disease and comparison participants. Rigorous study designs will allow for a better understanding of the potential role of the microbiome in endometriosis etiology and the relationship to other disorders of the female reproductive tract. 10.1093/humupd/dmab035

Correlation between dysbiosis of vaginal microecology and endometriosis: A systematic review and meta-analysis. PloS one BACKGROUND:Endometriosis, a complex gynecological condition, involves inflammation and immune dysregulation. The vaginal microbiota, characterized by its diversity, is an integral part of the vaginal microecology-interacting with vaginal anatomy, the endocrine system, and local mucosal immunity. Imbalances in this microecology are known to precipitate various inflammatory diseases. Despite extensive research, the connection between vaginal microbiota dysbiosis and endometriosis remains a subject of debate. Our study assesses the association between vaginal microecology dysbiosis and endometriosis. METHODS:We systematically searched major electronic databases in English, including Embase, PubMed, The Cochrane Library, MEDLINE (Ovid), BIOSIS (Ovid), China National Knowledge Infrastructure (CNKI), and Wanfang, up to August 15, 2023. Selected articles underwent screening based on predefined inclusion and exclusion criteria. Normal vaginal microecology was defined as a negative Amsel/Spiegel test or Nugent score of 0-3, or Lactobacillus predominance determined by 16S rRNA gene amplification sequencing. Deviations from this norm were classified as dysbiosis, further categorized into bacterial vaginosis (BV) and intermediate BV. Data analysis utilized Revman 5.4, with effect sizes presented as Odds Ratios (OR) and 95% Confidence Intervals (CI). RESULTS:Out of 1081 articles, eight met the inclusion criteria. Utilizing fixed-effect models due to low heterogeneity, the analysis revealed a positive association between dysbiosis and endometriosis (OR = 1.17, 95% CI 0.81-1.70; I2 = 0%), but showed a slight negative association between normal vaginal microecology with endometriosis (OR = 0.90, 95% CI 0.55-1.46; I2 = 29%). However, the association was not significant. Subgroup and sensitivity analyses corroborated the stability of these associations. CONCLUSION:A positive correlation exists between vaginal microecology dysbiosis and endometriosis, notably with intermediate BV. However, the mechanisms underpinning this relationship remain elusive, highlighting the need for further research to overcome limitations. TRIAL REGISTRATION:Registration number: CRD42023445163. 10.1371/journal.pone.0306780