Gut-peritoneal-multisystem axis in endometriosis

Article Text Statistics from Altmetric.com Endometriosis is a chronic multisystem inflammatory disease characterised by the presence of endometrial-like epithelium and stroma outside the uterine cavity, most commonly within the peritoneal cavity.1 Affecting approximately 10% of reproductive-aged women worldwide, the disease is associated with chronic pelvic pain, infertility and substantial impacts on quality of life and an increased risk of inflammatory bowel disease.2 Gastrointestinal symptoms, including nausea, abdominal pain, bloating (‘endo-belly’) and altered bowel habit, are frequently reported even without overt bowel lesions, highlighting gut-peritoneal interactions in this disease. For nearly a century, Sampson’s theory of retrograde menstruation has provided the prevailing explanation for disease initiation.3 According to this model, viable endometrial fragments reflux through the fallopian tubes into the peritoneal cavity during menstruation, where they may attach to peritoneal surfaces. However, retrograde menstruation occurs in most menstruating individuals whereas only a subset develop endometriosis. This discrepancy suggests that additional biological processes determine whether ectopic endometrial cells are cleared or instead survive and establish lesions. In addition, endometriosis can present shortly after menarche and persist after menopause, suggesting that processes beyond menstrual reflux sustain the inflammatory microenvironment enabling lesion persistence and associated symptoms. Superficial peritoneal disease accounts for most cases and can cause significant morbidity yet the number and size of visible lesions correlate poorly with symptom severity.1 Endometriotic lesions have been reported in nearly every organ and display several cancer-like hallmarks that support their survival and persistence, including oestrogen-driven hyperproliferation, progesterone resistance, impaired immunosurveillance … Footnotes Contributors FEA: visualisation, writing of the original draft. EMEO: visualisation, review of the original draft and guarantor. During the preparation of this work the authors used Claude AI to improve readability and language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests None declared. Provenance and peer review Commissioned; internally peer reviewed.