The Microbiome Landscape of Adenomyosis: A Systematic Review

Alterations in the microbiome composition have been identified in common gynecologic pathologies such as endometriosis carving a new frontier in diagnosis and treatment. We aimed to examine the existing literature on perturbations in the reproductive tract microbiome of individuals with adenomyosis informing future therapeutic targets. To examine the association between the reproductive tract microbiome composition among individuals with adenomyosis when compared to controls that can lead to new research evaluating novel mechanisms of action and treatment modalities. A systematic literature search identified studies that compared differences in microbiome composition using culture-independent microbiome analysis between individuals with adenomyosis when compared to controls. Five observational cross-sectional studies characterizing the lower and upper reproductive tract in humans were included. The diagnostic criteria of adenomyosis included surgical and imaging-based criteria. All studies used a 16S rRNA sequencing method. All individuals were recruited from either China or Thailand. An association between adenomyosis and alterations in the microbiome composition included relative deficiencies in Lactobacillus and relative enrichment of anaerobic and gram-negative bacteria when compared to control participants. Comparative studies suggest that there are significant perturbations in the microbiota composition of individuals with adenomyosis when compared with controls. Limiting conclusions include relative small sample sizes, a homogeneous population, and scant clinical phenotypic data. This systematic review identified significant alterations in the bacterial composition of adenomyosis cases that can be leveraged to design mechanistic studies and future innovative approaches to diagnose and manage this pathology. Trial registration: PROSPERO (CRD42023494563). Registered December 28, 2023. Similar content being viewed by others Data Availability Data will be made available to the editors of the journal for review or query upon request. Code Availability Not applicable.

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The authors would like to acknowledge librarian Ariel Pomputius (AP) for assisting with the systematic review search. Additionally, we would like to thank Prof. Christian Jobin and Dr. Javier Tamargo for providing resources. Funding None. Author information Authors and Affiliations Contributions AQ, TM, and MDD wrote the protocol; AP conducted the systematic search; TM and MDD independently screened articles, selected eligible studies, and extracted data. TM and MDD consulted AQ to resolve differences of opinion for eventual consensus. AQ, TM, MDD, and MWD collaborated to interpret the results and write the paper. Corresponding author Ethics declarations Ethics Approval Not applicable. Consent to Participate Not applicable. Consent for Publication All authors consent to the publication of the manuscript. Conflicts of Interest/Competing Interests AQ receives research support from the Bristol-Myers Squibb Foundation. MDD, MWD, TM do not have any conflicts of interest. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Prior Presentation: Data in the study has not been previously published or presented. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Dantzler, M.D., Miller, TA., Dougherty, M.W. et al. The Microbiome Landscape of Adenomyosis: A Systematic Review. Reprod. Sci. 32, 251–260 (2025). https://doi.org/10.1007/s43032-024-01766-7 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-024-01766-7