Gut Microbiota and Endometriosis: Exploring the Relationship and Therapeutic Implications

Abstract

Endometriosis is a common inflammatory disease affecting women of reproductive age, characterized by the growth of endometrial tissue beyond the uterus. In addition to gynecological manifestations, many endometriosis patients experience gastrointestinal symptoms, indicating a potential association between gut health and the disease. Recent studies have revealed alterations in the gut microbiota of individuals with endometriosis, including reduced diversity, microbial composition imbalances, and pathogenic bacteria. These changes can disrupt immune function, increase inflammation, and contribute to the chronic inflammatory state observed in endometriosis. Moreover, dysregulation of intestinal permeability may further exacerbate gastrointestinal symptoms in affected individuals. Understanding the role of the gut microbiota and intestinal permeability in endometriosis can provide valuable insights into disease pathogenesis, aid in non-invasive diagnostic approaches, and open new avenues for therapeutic interventions. Probiotics, in particular, have shown promise in improving endometriosis-associated pain symptoms and reducing endometriotic lesions in animal models. This review suggests that additional research and well-designed clinical trials are necessary to validate the potential diagnostic and therapeutic benefits of manipulating the gut microbiota in managing endometriosis and its gastrointestinal symptoms, thereby improving the quality of life for those affected.

Keywords: dysbiosis; endometriosis; estrogen; gut microbiota; leaky gut; probiotics.

Figure 1

Panel (A) shows the prevalence of dysmenorrhea, dyspareunia, dysuria, and dyschezia (the 4-D’s) (*) [20] and the prevalence of gastrointestinal symptoms (†) [14]. Panel (B) shows the processes involved in endometriosis, which can disrupt anatomical structures and impair reproductive function [7,8,9,10,11].

Figure 2

The figure displays the presence of an endometriosis implant on the rectum in a patient undergoing a transvaginal ultrasound at our San Martino Hospital in Genoa. This patient experienced symptoms including dyschezia, rectal tenesmus, alternating episodes of constipation and diarrhea, as well as painful intestinal spasms. The yellow calipers represent the measurements. The green one represents the ultrasound machine’s pointer.

Figure 3

This illustration depicts the role of zonulin in regulating intestinal permeability. Panel (A) illustrates the circumstances when a stable gut microbiota is present. The processes of transcellular antigen sampling by enterocytes and antigen sampling by luminal dendritic cells play a crucial role in regulating antigen trafficking between the intestinal lumen and the submucosa. This process ultimately determines whether the body develops tolerance or immunity toward non-self-antigens. Panel (B) depicts the conditions of gut dysbiosis that result in zonulin release, causing a transient opening of tight junctions. Chronic gut dysbiosis results in a shift from regulated antigen transportation to an elevated antigen transportation process dependent on zonulin due to alterations in gene expression associated with tight junctions. The heightened transportation of antigens results in an inflammatory response, which in turn augments the permeability of the gastrointestinal tract. This process leads to the production of pro-inflammatory cytokines, activation of T-cells, and a breakdown of immune tolerance in people with impairments in immunoregulation. Illustration created with BioRender.com.