Figure 2.

Schematic diagram of the mechanism of microbial involvement in endometriosis. (A) Endometriosis causes inflammation of the peritoneum, which suppresses gastric acid production and intestinal motility, allowing gram-negative bacteria to take over. (B) β-glucuronidase helps intestinal bacteria metabolize estrogen. β-glucuronidase activates and binds ERs. Gut dysbiosis increases the amount of estrogen that can be delivered to the endometrium via the bloodstream. (C) Endometrial tissue contains stem cells. Stem cells, which are normally mobile and migrate to the uterus, migrate to ectopic sites via the bloodstream, promoting uncontrolled formation of endometrial tissue outside the normal uterine environment, resulting in endometriosis. (D) Endometrial fragments that enter the peritoneum during retrograde menstruation produce damage-associated molecular pattern (DAMP) molecules, iron and ROS, activate innate immune cells, and release proinflammatory cytokines and angiogenic growth factors in the peritoneal fluid (PF). Interleukins increase the number of TH17 cells that drive hypervascularization. (E) The presence of bacteria in the uterine environment causes endometriosis by refluxing lipopolysaccharides (LPS) into the PF and binding to pattern recognition receptors (PRRs).