Uterine microbiome signatures associated with endometriosis

Background Endometriosis is a chronic inflammatory disorder affecting ~ 10% of reproductive-age women, often causing pelvic pain and infertility. Despite its prevalence, diagnosis remains delayed due to non-specific symptoms and lack of reliable non-invasive biomarkers. Emerging evidence implicates the microbiome in disease pathogenesis.

We analyzed uterine microbiomes from 266 tissue samples collected during either the proliferative or secretory phase, using 16S rRNA gene sequencing. Genus-level analysis revealed variable Lactobacillus abundance among all individuals. Prevotella showed borderline enrichment in proliferative-phase patients. Sub-genus analyses identified a small number of differentially abundant taxa, though none remained significant after FDR correction. To capture subtle microbial shifts, we developed a feature set combining weakly differential taxa, algorithmically selected taxa via machine learning, and a functional dysbiosis score. A supervised classifier trained on proliferative-phase data achieved moderate predictive performance (AUC = 0.70), while secretory-phase models performed more poorly (AUC = 0.58).

The uterine microbiome shows phase-dependent differences in its potential to inform endometriosis status. Although no robust individual microbial biomarkers were identified, machine learning models incorporating subtle community features from the proliferative phase yielded modest diagnostic potential. These results highlight the importance of menstrual cycle-aware sampling and support further development of microbiome-informed diagnostic tools for endometriosis. Similar content being viewed by others Abbreviations - BMI: - Body mass index - FDR: - False discovery rate - FDS: - Functional dysbiosis score - AUC: - Area under the curve - AI: - Artificial intelligence - rASRM: - Revised American Society for Reproductive Medicine

The authors would like to express their appreciation to Jonathan Zhao and Frank Zhang (both from HerAnova Lifesciences) for their insightful input on the study design and manuscript. Funding The research was funded by the internal R&D budget at HerAnova Lifesciences Inc, and by the National Key R&D Program of China (2022YFC2704003). Author information Authors and Affiliations Corresponding authors Ethics declarations Ethics approval and consent to participate This study was approved by the institutional review board of the Women’s Hospital, Zhejiang University School of Medicine (IRB-20240110-R), and consent was given by enrolled participants. Consent for publication The enrolled participants provided informed consent for the use of their biological materials in research and publication. All authors have reviewed and approved this manuscript for publication. Competing interests All authors, except Zhang Xinmei and Zhu Libo, are employees of HerAnova Lifesciences, a company engaged in the commercial development of a non-invasive test for endometriosis. Farideh Z Bischoff, Yanqin Yu and Wing Hing Wong hold stock options of HerAnova Lifesciences. The authors declare no other conflicts of interest, financial or otherwise. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information 12915_2026_2659_MOESM1_ESM.docx (download DOCX ) Additional file 1: Tables S1-S8. Table S1. Comparison of ALDEx2 results with MaAsLin2 in proliferative phase. Table S2. Selected taxa in proliferative cohort by random forest scoring. Table S3. Selected taxa in secretory cohort by random forest scoring. Table S4. Functional dysbiosis score of all participants. Table S5. Feature set of proliferative cohort. Table S6. Feature set of secretory cohort. Table S7. Clinical information of participants in the study. Table S8. Taxa identified in negative controls, including spike-in taxa. 12915_2026_2659_MOESM2_ESM.xlsx (download XLSX ) Additional file 2: Figures S1-S2. Figure S1. Subgroup analysis stratified by disease stages. Figure S2. Within-group comparisons of proliferative and secretory phases. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Zhu, L., He, J., Xu, X. et al. Uterine microbiome signatures associated with endometriosis. BMC Biol (2026). https://doi.org/10.1186/s12915-026-02659-8 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12915-026-02659-8