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.

A Systematic Review of Anogenital Distance and Gynecological Disorders: Endometriosis and Polycystic Ovary Syndrome

“…Our systematic review results support the hypothesis that a shortened AGD increases the risk of fecal microbial contamination of the vulva and vagina, resulting in a cervicovaginal microbial imbalance, a subclinical inflammatory response, and then endometriosis (14). Khan et al found elevated levels of Escherichia coli in the menstrual blood of endometriosis patients, suggesting that elevated endotoxin in the peritoneal fluid may promote endometriosis progression via Toll-like receptor (TLR)-4 (38). None of these factors have been definitively shown to have a cause-effect relationship with endometriosis, so it is reasonable to explore additional potential risk factors.…”

A More Diverse Cervical Microbiome Associates with Better Clinical Outcomes in Patients with Endometriosis: A Pilot Study

“…For examples, treating chronic endometritis with antibiotics or uterine lavage has been demonstrated effective to increase conception rates in women of reproductive age [ 76 , 77 ]. On the other hand, because microbes in the gut have huge impacts on female reproductive tract [ 19 , 20 , 21 , 22 , 23 ], diet-induced microbiota remodeling is considered as another possible therapeutic strategy for treating endometriosis. Studies have indicated that women with high intakes of omega-3 unsaturated fatty acids (PUFAs) have a lower risk of developing endometriosis [ 78 , 79 ]; similar dietary benefits have been also shown in mouse studies, resulting in better anti-inflammatory effects and reduced endometriosis formation [ 80 , 81 ].…”

“…For examples, gut bacteria has been known to show great impacts on central neuron system, hormone system and other extraintestinal organs of the host, such as the reproductive system [ 19 , 20 ]. Dysbiosis in gut tract has been found to significantly increase estrogen levels in the circulation, which can subsequently stimulate growth of ectopic endometriotic cells and promote inflammatory activity [ 21 , 22 , 23 ].…”

“…Several attempts have been made to investigate the microbiota continuum along the female reproductive tract and their impacts on the development of endometriosis [ 23 , 24 , 25 ]. Some species were frequently linked with endometriosis development, including increased Streptococcus, Pseudomonas and Enterobacteriaceae with diminished Atopobium [ 26 , 27 , 28 ].…”

Vaccination of Gilthead Seabream After Continuous Xenoestrogen Oral Exposure Enhances the Gut Endobolome and Immune Status via GPER1

“…Besides, the relationships between gut microbial richness, systemic and fecal estrogens, and beta-glucuronidase activity have been demonstrated ( 67 ). Based on these concepts, the term estrobolome was coined to define the gene repertoire of the gut microbiota capable of metabolizing estrogens ( 28 , 76 ). However, just recently, the wider term endobolome was also suggested to address the group of gut microbiota, genes, and pathways involved in the metabolism of any EDC, including the target of this study, the EE 2 ( 29 ).…”