Intricate Connections between the Microbiota and Endometriosis

Abstract

Imbalances in gut and reproductive tract microbiota composition, known as dysbiosis, disrupt normal immune function, leading to the elevation of proinflammatory cytokines, compromised immunosurveillance and altered immune cell profiles, all of which may contribute to the pathogenesis of endometriosis. Over time, this immune dysregulation can progress into a chronic state of inflammation, creating an environment conducive to increased adhesion and angiogenesis, which may drive the vicious cycle of endometriosis onset and progression. Recent studies have demonstrated both the ability of endometriosis to induce microbiota changes, and the ability of antibiotics to treat endometriosis. Endometriotic microbiotas have been consistently associated with diminished Lactobacillus dominance, as well as the elevated abundance of bacterial vaginosis-related bacteria and other opportunistic pathogens. Possible explanations for the implications of dysbiosis in endometriosis include the Bacterial Contamination Theory and immune activation, cytokine-impaired gut function, altered estrogen metabolism and signaling, and aberrant progenitor and stem-cell homeostasis. Although preliminary, antibiotic and probiotic treatments have demonstrated efficacy in treating endometriosis, and female reproductive tract (FRT) microbiota sampling has successfully predicted disease risk and stage. Future research should aim to characterize the "core" upper FRT microbiota and elucidate mechanisms behind the relationship between the microbiota and endometriosis.

Keywords: Lactobacillus; antibiotics; dysbiosis; endometriosis; estrobolome; estrogen; gut microbiota; immune dysregulation; inflammation; metabolome; microbiota; probiotics; uterine microbiota; vaginal microbiota.

Figure 1

Aetiology and pathogenesis of endometriosis.

Figure 2

Altered estrobolome activity and upregulated enzyme expression produces a hyperestrogenic environment that promotes endometriosis onset and progression.

Figure 3

The Firmicutes/Bacteroidetes ratio, an indicator of dysbiosis, is altered in endometriosis patients.

Figure 4

Antibiotic treatment can reduce endometriotic lesion growth and peritoneal inflammation, and subsequent faecal microbiota transfer from diseased mouse can restore lesion growth and inflammation. Mouse experiment demonstrates bidirectional relationship between endometriosis and gut microbiota.

Figure 5

(A). The microbiota regulates factors involved in maintaining normal peritoneal environment and ectopic cell clearance. (B). Dysbiosis contributes to the dysregulation of factors driving endometriosis onset and progression.

Figure 5

(A). The microbiota regulates factors involved in maintaining normal peritoneal environment and ectopic cell clearance. (B). Dysbiosis contributes to the dysregulation of factors driving endometriosis onset and progression.

Figure 6

Summary of current limitations, future directions and possible outcomes.