The Endobiota-estrobolome Study in Reproductive aged Women with Ovarian Endometriosis

Background The human body harbors greater than 10 trillion symbiotic, microbial cells that contribute to our bodily functions. Emerging evidences suggest that dysbiosis, especially of the gut or urogenital system, may induce various pathological conditions or altered estrobolome and associate with certain estrogen-dependent diseases like endometriosis. The present case-control study analyzed the enzymatic expressions, bacterial compositions, and variations of estrogen metabolites in fecal, vaginal, and urinary samples of patients with or without ovarian endometriosis. Methods A total of 38 women of reproductive age, 24 with pathologically-proven ovarian endometriosis and 14 without (control), were analyzed. Recruited patients provided stool, urine, and vaginal samples before undergoing surgeries for ovarian endometriosis or other benign ovarian tumors. Gut enzymatic assays of β-glucuronidase and β-glucosidase were conducted using an ELISA spectrophotometer. Advanced liquid chromatography and mass spectrometry analyzed estrogen and 14 estrogen metabolites in stool, urine, and vaginal samples. Gut and vaginal microbiota were detected with 16S ribosomal-RNA gene sequencing and further classified with Institute of Genome Sciences bioinformatics pipeline. Analyses for species composition, diversity, and abundance were compared between the ovarian endometriosis and control groups. Statistical significance was determined using t-tests and Wilcoxon tests ( p  < 0.05). Results While similar gut β-glucuronidase activities, microbial diversity, and abundance were observed in the fecal samples of both groups, the gut microbiota of the control group showed higher prevalence of Rothia genus whereas genera such as Megamonas , [ Eubacterium ] coprostanoligenes_group , Allisonella , Ruminiclostridium_5 , [ Eubacterium ] hallii_group , and Negativibacillus were significantly more abundant in the ovarian endometriosis group. Meanwhile, besides statistically lower folds of 4-methoxyestrone ( p  = 0.046), 2-methoxyestrone ( p  = 0.043), and 2-hydroxyestrone-3-methyl ether ( p  = 0.006), vaginal samples of patients with endometriosis also revealed significantly lower bacterial abundance, diversity, richness, and evenness. Conclusions While the current findings did not demonstrate obvious dysbiosis in patients with ovarian endometriosis, variations in certain genera and families of bacteria between the two groups could indicate altered estrogen metabolism or disturbed urogenital and gastrointestinal microbiota.