Did you know...the vaginal microbiome is connected to endometriosis?

Did you know...the vaginal microbiome is connected to endometriosis?

In this month's Did You Know? series, Chief Science Officer Beth DuPriest, PhD shares recent research examining microbiome differences between women with and without endometriosis. Studies show testing for variances in bacteria may eventually provide insight on disease pathogenesis, methods for diagnosis, and possibly even prevention of progression of this complex condition.

Q: How does the vaginal biome relate to endometriosis?

Endometriosis affects up to 10% of women. First described in the scientific literature over 100 years ago, its etiology remains undetermined1. It has a high impact on women and their partners, considering that 30-50% of women with endometriosis experience infertility2, and 50% report a decreased ability to work because of the condition3,4. But how does endometriosis relate to the vaginal microbiome? Recent research is beginning to shed light on this question.

Given the difficulty in diagnosing endometriosis non-invasively, it would be ideal if the vaginal microbiome could be used to differentiate healthy women from those with endometriosis. Unfortunately, this has not yet been accomplished, but there are some interesting and potentially useful signatures. Ata et al5 showed that, compared with healthy women, those with Stage 3 or 4 endometriosis had higher levels of Gardnerella (after excluding Lactobacilli). Sneathia, Streptococcus, Escherichia/Shigella, and Ureaplasma were also enriched in both the vaginal and cervical biomes. Interestingly, Atopobium vaginae, a hallmark of bacterial vaginosis, was absent in women with severe endometriosis. Perrotta et al6 were able to distinguish between women with mild (Stage 1 or 2) vs. severe (Stage 3 or 4) disease based on the vaginal microbiome; Anaerococcus was the main differentiating factor. Unfortunately, healthy women were intermediate between the two, and differences were not great enough to be useful as a diagnostic characteristic. Severity of dyspareunia in women with endometriosis was increased when the endocervical biome included high levels of Ureaplasma parvum, while Mycoplasma genitalium was correlated with higher markers of inflammation7. It seems that there are some differences in the biome between women with “endo” and those without, and certainly some based on severity of disease, but exactly what the fundamental differences are remains to be elucidated.

It is clear, however, that the cervix does not present an insurmountable barrier to bacteria; vaginal contents can traverse into the endometrial space within minutes. There are those who believe that ascending bacteria contribute to the etiology and/or pathogenesis of endometriosis. This “bacterial contamination theory” suggests that endotoxin-producing pathogens – especially E. coli – activate inflammatory pathways that increase the ability of ectopic endometrial tissue segments (from retrograde menstruation or possibly other mechanisms) to implant on the peritoneum and to proliferate8. Cross-talk between estradiol and the toll-like receptor (TLR) 4 pathway, stimulated by endotoxin, synergizes to promote the development of endometrial lesions. If true, this hypothesis might predict that the progression of endometriosis could be mitigated by improving the vaginal microbiome to lower endotoxin levels and reduce inflammation. Currently no data exist to evaluate the merit of this idea.

What is most clear about the connection between the microbiomes of the female reproductive tract and endometriosis is that more high-quality research needs to be done. Understanding how the vaginal microbiome contributes to, or at least reflects, the presence and severity of endometriosis will help make progress toward treatment and diagnosis of the condition.



1. Benagiano G, Brosens I, Lippi D. The History of Endometriosis. Gynecol Obstet Invest. 2014;78(1):1-9. doi:10.1159/000358919

2. Sperschneider ML, Hengartner MP, Kohl-Schwartz A, et al. Does endometriosis affect professional life? A matched case-control study in Switzerland, Germany and Austria. BMJ Open. 2019;9(1):e019570. doi:10.1136/bmjopen-2017-019570

3. Fagervold B, Jenssen M, Hummelshoj L, Moen MH. Life after a diagnosis with endometriosis - a 15 years follow-up study. Acta Obstet Gynecol Scand. 2009;88(8):914-919. doi:10.1080/00016340903108308

4. De Graaff AA, D’Hooghe TM, Dunselman GAJ, et al. The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey. Hum Reprod. 2013;28(10):2677-2685. doi:10.1093/humrep/det284

5. Ata B, Yildiz S, Turkgeldi E, et al. The Endobiota Study: Comparison of Vaginal, Cervical and Gut Microbiota Between Women with Stage 3/4 Endometriosis and Healthy Controls. Sci Rep. 2019;9(1):2204. doi:10.1038/s41598-019-39700-6

6. Perrotta AR, Borrelli GM, Martins CO, et al. The Vaginal Microbiome as a Tool to Predict rASRM Stage of Disease in Endometriosis: a Pilot Study. Reprod Sci. 2020;27(4):1064-1073. doi:10.1007/s43032-019-00113-5

7. Campos GB, Marques LM, Rezende IS, Barbosa MS, Abrão MS, Timenetsky J. Mycoplasma genitalium can modulate the local immune response in patients with endometriosis. Fertil Steril. 2018;109(3):549-560.e4. doi:10.1016/j.fertnstert.2017.11.009

8. Khan KN, Fujishita A, Hiraki K, et al. Bacterial contamination hypothesis: a new concept in endometriosis. Reprod Med Biol. 2018;17(2):125-133. doi:10.1002/rmb2.12083

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