The objective of this study was to systematically review the literature on the human microbiome in association with endometriosis. PubMed/Medline, Cochrane, and Embase databases were searched for literature published from 1986 to August 2021. All human studies that assessed the microbiome using 16S rRNA sequencing or shotgun sequencing in women with endometriosis were included. Two reviewers independently abstracted data from the selected articles into tables. To assess the quality of included studies, the National Institutes of Health Study Quality Assessment Tools were utilized. This review included 12 case–control studies. Included studies compared the microbiome from various anatomical sources (fecal, vaginal, cervical, peritoneal, endometrial, and intra-lesional) between patients with endometriosis and a heterogeneous set of control patients. Study quality ranged from poor to good, with 8 of 12 studies rated fair. Multiple studies reported a different distribution of bacteria among women with endometriosis across anatomical sites, but the results were highly heterogeneous. Pseudomonas was overrepresented in peritoneal fluid among women with endometriosis across multiple studies but was also observed to be increased in vaginal, endometrial, and intra-lesional samples. Among bacteria noted across different anatomical samples, Gardnerella was found to be increased in cervical but decreased in endometrial, fecal, and vaginal samples of patients with endometriosis, while Atopium was found to be decreased in vaginal and cervical samples from patients with endometriosis. Sphingobium was found to be increased in vagina, endometrium, and peritoneal fluid from patients with endometriosis. Streptococcus was found to be increased in peritoneal, endometrial, and cervical samples from women with endometriosis. Microbiomal comparisons stratified by endometriosis stage or site of endometriosis involvement were limited and highly heterogeneous.Lay summaryThe microbiome, a group of bacteria found in a particular place in the body, has been shown to vary when patients have some diseases, such as cancer or inflammatory bowel disease. Less is known about the microbiome in patients with endometriosis. This review looked at existing studies comparing the bacteria found in patients with endometriosis and others without. Twelve studies were found that assessed the bacteria from swabs collected from different places, including the vagina, cervix, endometrium, peritoneum, feces, and endometriosis lesions themselves. Most of the studies found higher or lower levels of specific bacteria at each of these places, but the findings were often inconsistent. The findings were probably limited by the small numbers of patients involved and variations in the groups studied. More research is needed to find out which bacteria are over- and underrepresented in patients with endometriosis and where they are found.
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