Myometrial Microbiome in Uterine Fibroids: Functional Dysbiosis Versus Limited Taxonomic Change

Background: Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age and are associated with abnormal uterine bleeding, infertility, and impaired implantation and endometrial receptivity. However, the contribution of the myometrial microbiome (MM) to fibroid biology and the broader uterine environment remains poorly understood. Materials and Methods: We characterized the paired MM of UF tissue and adjacent healthy myometrium (HM) from 21 women undergoing surgery and integrated serum free fatty acid (FFA) and cytokine profiling. Results: Taxonomic composition and microbial diversity were highly similar between tissues, with no differentially abundant taxa after multiple-testing correction. In contrast, PICRUSt2-based functional prediction indicated tissue-specific differences in microbial metabolic potential: UF tissue showed higher predicted representation of pathways related to L-tyrosine biosynthesis and aromatic amine degradation, whereas HM showed higher predicted representation of coenzyme A and arginine biosynthesis pathways. Patients also exhibited distinct circulating FFA profiles compared with healthy women, and integrative analyses identified phenotype-specific associations among microbial taxa, FFAs, and inflammatory mediators, particularly in women with heavy menstrual bleeding or specific fibroid localizations. Conclusions: These findings suggest that UFs are associated with potential functional remodeling of the MM rather than major taxonomic alterations, which may contribute to changes in the uterine environment relevant to implantation, endometrial receptivity, and reproductive health.