A closer look at the role of common bacteria in the development of endometriosis

Endometriosis is a chronic multisystemic condition, characterised by the presence of endometrial-like tissue growing outside of the uterus. Endometriosis affects approximately 10-15% of women and those assigned female at birth of reproductive age globally, however, uncertainty surrounds its true prevalence due to non-specific symptoms such as painful and heavy periods, chronic pelvic pain, and infertility. Furthermore, as the cause of endometriosis is unknown, diagnosis can be a difficult and lengthy process, with the average diagnosis time for endometriosis in the UK being eight years.¹

In a recent study conducted at Nagoya University in Japan, researchers examined endometrial and endometriosis tissue samples collected from women with and without endometriosis.² The analysis revealed that Fusobacterium nucleatum, a type of bacteria, was present in 64% of the samples from women diagnosed with endometriosis, whereas it was found in only 7% of the samples from women without the condition. Additionally, an increase in the presence of Fusobacterium was observed in vaginal swab samples obtained from patients diagnosed with endometriosis when compared to those without the condition.

The study, published in Science Translational Medicine, then used a mouse model of endometriosis to investigate the role of F. nucleatum in endometriosis further. When the bacteria was introduced to the mouse model of endometriosis, the number and size of endometrial “lesions” had increased in comparison to mice that were not infected with the bacteria. Interestingly, when the researchers administered antibiotics to the mice infected with the bacteria, they observed that it prevented the growth of infected endometrial tissue.

The Fusobacterium species of bacteria are commonly present in the oral and gut microbiome of humans and is known as a symbiont organism, which is an organism that uses another organism as a habitat.³ This relationship can be either beneficial or detrimental. For example, in some humans, F. nucleatum can contribute to gum disease and can also have implications for the conversion of normal cells into cancer cells.⁴ However, the mechanism by which the bacteria enters the uterus, considering its nearly sterile nature, remains unclear. Some studies have suggested that intrauterine infection by F. nucleatum could occur through blood transmission from the mouth during pregnancy,⁵ or transmission via the vagina.

Whilst the findings of this study are intriguing, there are still some crucial elements missing. The study transplanted endometrial tissue into mice, as opposed to endometriotic tissue, disregarding the distinct differences between the two.² Consequently, the data is not generalisable and cannot be applied to endometriosis in humans. Although the presence of bacteria in the mouse model of endometriosis appeared to increase the number and size of the “lesions”, it is not necessarily causative, and may well just be a chance occurrence.

The study also revealed that 64% of the patients diagnosed with endometriosis had detectable levels of F. nucleatum in their tissue samples.² As not all patients with endometriosis had F. nucleatum present in their samples, this finding supports the notion that endometriosis is a complex disease with multiple contributing factors rather than a condition caused by a single factor. Moreover, it's important to consider that other bacteria present in the vagina might also play a role in the development of endometriosis, however, this is currently unknown. 

It is also worth noting that antimicrobial resistance is another issue that should be taken into account when exploring potential treatment options for endometriosis. Antimicrobial resistance is a current global public health issue that impacts the effectiveness of antibiotics. The misuse of antibiotics, including incorrect dosages and genetic factors, has contributed to the widespread emergence of multidrug-resistant bacteria, making the treatment of infections increasingly challenging.⁶ If endometriosis is caused by a Fusobacterium infection, the consideration of long-term antibiotic use as a treatment option raises concerns regarding the ongoing antimicrobial resistance crisis. With antimicrobial resistance already posing a significant threat to global public health, the indiscriminate use of antibiotics for endometriosis treatment could further exacerbate the problem.

Despite this, it is encouraging to see that research is gradually moving away from the outdated theory of retrograde menstruation as the primary cause of endometriosis. Further research is necessary to determine the overall role of bacteria in the development of endometriosis in humans, which could pave the way for updated treatment options that go beyond hormonal remedies.

Endometriosis patients are not seeking short-term or temporary solutions for their long-term challenges; rather, they desire the active engagement and collaboration of the medical and research communities to remove barriers that hinder their ability to benefit from research directly, with a focus on enhancing access to quality treatment and care.

This article was first published on 21st June 2023.

Reference List 

1. Endometriosis in the UK: Time for Change [Internet]. All Party Parliamentary Group on Endometriosis ; 2020 [cited 2023 Jun 20]. Available from: https://www.endometriosis-uk.org/sites/default/files/files/Endometriosis%20APPG%20Report%20Oct%202020.pdf
2. Muraoka A, Suzuki M, Hamaguchi T, Watanabe S, Iijima K, Yoshiteru Murofushi, et al. Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts. 2023 Jun 14;15(700). 
3. Overstreet RM, Lotz JM. Host–Symbiont Relationships: Understanding the Change from Guest to Pest. The Rasputin Effect: When Commensals and Symbionts Become Parasitic [Internet]. 2016 Jan 6 [cited 2021 Oct 15];3:27–64. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123458/
4. Brennan CA, Garrett WS. Fusobacterium nucleatum — symbiont, opportunist and oncobacterium. Nature Reviews Microbiology. 2018 Dec 13;17(3):156–66.
5. Vander Haar EL, So J, Gyamfi-Bannerman C, Han YW. Fusobacterium nucleatum and adverse pregnancy outcomes: Epidemiological and mechanistic evidence. Anaerobe. 2018 Apr;50:55–9.
6. Mobarki N, Almerabi B, Hattan A. Antibiotic resistance crisis. Int. J. Med. Dev. Ctries. 2019;40(4):561-4