Functional biomarkers for endometriosis targeting small RNAs in bacterial extracellular vesicles

Ayako Muraoka, Akira Yokoi, Kosuke Yoshida, Juntaro Matsuzaki, Eri Inami, Bayasula, Masami Kitagawa, Natsuki Miyake, Reina Sonehara, Tomoko Nakamura, Satoko Osuka, Hiroaki Kajiyama
In: Heliyon · 2025 · vol. 11(16) , pp. e44099 · doi:10.1016/j.heliyon.2025.e44099 · W4415903939
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Bacterial extracellular vesicles from <em>Fusobacterium nucleatum</em> altered host cell behavior, and specific small RNAs within these vesicles showed diagnostic potential for endometriosis in serum samples.

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Abstract

Abstract Extracellular vesicles (EVs) are secreted from mammalian cells and bacteria and are involved in disease pathogenesis. Recently, bacterial factors have been linked to the pathogenesis of endometriosis. Therefore, identifying host-bacterial interactions is crucial for a better understanding of endometriosis. Here, we isolated bacterial EVs (BEVs) from six species of common vaginal bacteria and analyzed their components by comprehensive small RNA sequencing. We then examined the influence of these BEVs on host cells. We showed that BEVs from Fusobacterium nucleatum (F. nuc.), an endometriosis-associated bacterium, significantly stimulated the migration ability of endometrial mesenchymal cells (P < 0.01). Exposure of dTHP-1 cells to BEVs form F. nuc. enhanced cytokine secretion and may induce the polarization of M2 macrophages over the M1 phenotype. We also investigated the potential of BEVs as biomarkers. We detected 40 specific RNA sequences that are both expressed in over 0.01 % of BEVs from F. nuc. and that were detected in >10 read counts in the serum of patients with endometriosis, but not in tissue samples. Serum samples from patients with endometriosis (n = 14) showed aberrant expression of six specific genes compared to patients without endometriosis (n = 34), and the receiver operating characteristic curve indicated that a combination of these six genes was most accurate for the diagnosis of endometriosis (area under the curve = 0.91). Small RNAs in BEVs may serve as novel biomarkers to detect endometriosis-related bacterial factors.

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endometriosis

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