Alterations in the uterine microbiome drive the progression of endometriosis via neutrophil-mediated AKT-mTOR signaling pathway.

Background The microbiome of the female reproductive system has been extensively studied; however, the correlation between uterine microbial alterations and endometriosis remains unclear. Methods Endometrial and lesion tissues were collected from patients with endometriosis, followed by 16S rRNA sequencing and RNA sequencing. The sequencing data were analyzed via PCA, random forest analysis, PICRUSt2 functional prediction, as well as GO and KEGG enrichment analyses, and further validated using the GEO database. Finally, the presence of the identified mechanism was confirmed in the pathological sections of endometriosis patients. Results we report that alterations in microbiome abundance were observed in both the endometrium and chocolate cysts of endometriosis patients, which promote the migration, proliferation, and pro-angiogenic capacity of endometrial cells. This process relies on the microbiome-immune cell-target cell axis, wherein abnormal microbiota induced neutrophil infiltration and the release of amounts of neutrophil extracellular traps (NETs), inflammatory cytokines, and chemokines. RNA-seq analysis further revealed that excessive inflammation subsequently activated the AKT-mTOR signaling pathway in endometrial cells, leading to enhanced cell adhesion and angiogenic phenotypes. Conclusion our study suggests that uterine microbiome changes are involved in the onset and progression of endometriosis and may offer a new perspective for its treatment.