Causation Could endometriosis be caused by bacteria? Link to bacterial infection suggests a potential way to treat the painful disorder. (Jun 2023, n=155) Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts

Michael Harrop

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Article:
Link to bacterial infection suggests a potential way to treat the painful disorder. https://www.nature.com/articles/d41586-023-01956-4

Study:
Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts https://www.science.org/doi/10.1126/scitranslmed.add1531

Abstract
Retrograde menstruation is a widely accepted cause of endometriosis. However, not all women who experience retrograde menstruation develop endometriosis, and the mechanisms underlying these observations are not yet understood. Here, we demonstrated a pathogenic role of Fusobacterium in the formation of ovarian endometriosis. In a cohort of women, 64% of patients with endometriosis but <10% of controls were found to have Fusobacterium infiltration in the endometrium. Immunohistochemical and biochemical analyses revealed that activated transforming growth factor–β (TGF-β) signaling resulting from Fusobacterium infection of endometrial cells led to the transition from quiescent fibroblasts to transgelin (TAGLN)–positive myofibroblasts, which gained the ability to proliferate, adhere, and migrate in vitro. Fusobacterium inoculation in a syngeneic mouse model of endometriosis resulted in a marked increase in TAGLN-positive myofibroblasts and increased number and weight of endometriotic lesions. Furthermore, antibiotic treatment largely prevented establishment of endometriosis and reduced the number and weight of established endometriotic lesions in the mouse model. Our data support a mechanism for the pathogenesis of endometriosis via Fusobacterium infection and suggest that eradication of this bacterium could be an approach to treat endometriosis.

Editor’s summary
Although endometriosis is a common disease affecting up to 15% of women of reproductive age, the mechanisms underlying the disease are not fully understood. Here, Muraoka and colleagues identified a potential infectious contributor to endometriosis. Fusobacterium was found in the endometrium and endometrial lesions of more than half of patients with endometriosis, but only 7% of controls. In a mouse model of endometriosis, inoculation of Fusobacterium increased the numbers and weights of endometriotic lesions, whereas antibiotic treatment with metronidazole and chloramphenicol could reduce the lesions. These findings suggest that Fusobacterium infection may contribute to the pathogenesis of endometriosis and that antibiotic treatment to eradicate endometrial infection should be further studied.--Melissa Norton
 
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