Dysbiosis of Gut Microbiota Contributes to Chronic Stress in Endometriosis Patients via Activating Inflammatory Pathway

Background: Gut microbiota can interact with the central nervous system through the gut-brain axis, thus affecting the host's chronic stress level, such as anxiety and depression. Current researches show that patients with endometriosis often have a high level of chronic stress, which will in turn aggravate endometriosis by activating the β-adrenergic signaling pathway. Therefore, we wondered whether the gut microbiota associates with the chronic stress level in endometriosis patients, which may provide new insights on how to improve treatment. Methods: We grouped the endometriosis patients into the chronic stress group and the control group with questionnaires such as generalized anxiety disorder-7 and patient health questionnaire-9 and collected patients' fecal specimens and tissue specimens. Gut microbiota compositions were analyzed by the 16SrRNA gene sequencing-based method, and immunohistochemistry was performed to detect the activation of inflammatory pathways in endometriosis tissues. Results: We found that in patients with endometriosis, the dysbiosis of gut microbiota was associated with their stress levels. Furthermore, the levels of Paraprevotella, Odoribacter, Veillonella, and Ruminococcus were significantly reduced in chronic stressed endometriosis patients, suggestive of a disease-specific change of gut microbiota at the genus level. Compared to the healthy women, the expression levels of inflammatory cytokines, nuclear factor-κB p65, and cyclooxygenase-2 increased in the chronic stressed endometriosis patients, indicating that the dysbiosis of gut microbiota may activate the inflammatory pathway of gut-brain axis. Conclusions: We hypothesized that these new disease-specific changes of gut microbiota in chronic stressed patients with endometriosis may be a new examination target of chronic stress level. These changes may also provide new insights for psychological intervention, thus reducing the stress level and improving the prognosis of endometriosis patients.