Background and Objectives: Endometriosis is a chronic, estrogen-dependent inflammatory disease with multifactorial pathogenesis. Increasing evidence suggests that alterations in the gut and reproductive tract microbiota may contribute to disease development, progression, and associated symptoms through immune, hormonal, and metabolic mechanisms. This systematic review aimed to synthesize current human evidence on microbiota composition and function in women with endometriosis. Materials and Methods: A systematic literature search was conducted according to PRISMA 2020 guidelines across PubMed, Embase, Web of Science, Scopus, and the Cochrane Library. Observational human studies published in English between January 2015 and September 2025 evaluating gut, vaginal, cervical, endometrial, or peritoneal microbiota in women with endometriosis were included. Two reviewers independently screened studies, extracted data, and performed a qualitative synthesis due to methodological heterogeneity. Results: Nineteen studies were included, encompassing gut and reproductive tract samples analyzed primarily by 16S rRNA sequencing. Across cohorts, endometriosis was consistently associated with microbial dysbiosis characterized by enrichment of Proteobacteria and Firmicutes and depletion of Bacteroidetes, Lactobacillus, and Bifidobacterium. Increased abundance of opportunistic taxa, particularly Escherichia coli, Streptococcus, and Klebsiella, was frequently reported. Functionally, dysbiosis was linked to increased β glucuronidase activity, enhanced estrogen enterohepatic recirculation, reduced short-chain fatty acid production, and activation of pro-inflammatory immune pathways. Several studies reported correlations between microbial profiles, disease stage, pelvic pain, and infertility. Conclusions: Current evidence supports a reproducible association between gut microbiota dysbiosis and endometriosis. Altered microbial composition and function may contribute to chronic inflammation, hormonal imbalance, and disease persistence. Longitudinal and multi-omic studies are needed to clarify causality and to evaluate microbiota-based diagnostic and therapeutic strategies.
Crestani et al. (Tue,) studied this question.