The role of gut microbiota in modulating estrogen in the inflammatory milieu of endometriosis: A molecular and pathophysiological perspective

Endometriosis is a prevalent estrogen-dependent chronic inflammatory condition that affects millions of women of reproductive age worldwide. It is characterized by the growth of endometrial tissue outside the uterine cavity, which leads to persistent inflammation, pain, and infertility. It is a multifaceted condition with a poorly understood etiology and pathogenesis resulting from several aberrant biological processes. Among these, elevated estrogen levels are considered the primary trophic factors. Intracrine estrogen biosynthesis by endometriotic lesions, anomalous expression of estrogen receptors and enzymes, and dysregulation of estrogen metabolism collectively contribute to the chronic inflammatory milieu of endometriosis. Inflammation further sustains these activities and perpetuates a vicious cycle. Gut microbiota homeostasis has emerged as a key modulator of estrogen metabolism and inflammation in several estrogen-sensitive diseases. A bidirectional interaction between gut microbiota and endometriosis has been reported. This review aimed to explore the potential role of gut dysbiosis in circulating estrogen levels, inflammation, and oxidative stress in endometriosis. Understanding the interactions between estrogen, inflammatory pathways, and the gut microbiota may help in the early detection of endometriosis through specific microbial and inflammatory biomarkers. Additionally, this may pave the way for the development of personalized treatment plans based on individual microbial profiles and hormonal status, and to enhance clinical practice by guiding anti-inflammatory microbes in probiotic therapies and identifying effective prebiotic treatments.