NEW YORK – New research suggests bacteria may spur on the development of endometriosis, a condition marked by tissue growth outside of the endometrial cavity.
In particular, the team's findings — published in Science Translational Medicine on Wednesday — highlighted a role for Fusobacterium infection in the cellular transitions leading to endometriosis.
Prior research had linked endometriosis risk to a process known as retrograde menstruation, which involves backwards menstrual blood movement into the fallopian tubes and pelvic cavity rather than out of the body via the vagina. Even so, endometriosis does not always turn up in individuals experiencing retrograde menstruation, which is relatively common in reproductive-age women, senior and corresponding author Yutaka Kondo, a cancer biologist at Nagoya University, said in an email.
"This suggests the existence of other specific mechanisms in the endometrium that facilitate the development of endometriosis in patients," Kondo explained, noting that "there is no conclusive explanation about this question so far."
With that in mind, he and his colleagues turned to gene expression profiling, single-cell RNA sequencing, and fluorescence in situ hybridization (FISH) to assess uterus endometrial fibroblast and ovarian endometriotic lesion samples from individuals with endometriosis and samples from unaffected controls. They used FISH probes informed by publicly available bacterial 16S ribosomal RNA databases to search for Fusobacterium species found in some vaginal samples in past studies.
"In this study, we asked whether the endometrial stromata of patient with endometriosis contained different types of fibroblasts compared with people without endometriosis, and whether these fibroblasts might be associated with the presence of specific pathogenic bacteria," the authors explained.
The team saw signs of Fusobacterium infection in more than 64 percent of tissue samples from individuals with endometriosis. In contrast, the bug turned up in just over 7 percent of samples from endometriosis-free subjects.
With the help of follow-up immunohistochemistry, chromatin immunoprecipitation-qPCR, cytokine profiling, mouse modeling, and other experiments, the team suggested that Fusobacterium infection can boost transforming growth factor beta (TGF-beta) activation, prompting quiescent fibroblast cells to become myofibroblast cells expressing a cytoplasmic microfilament-associated protein known as transgelin (TAGLN).
The TAGLN-positive cells, in turn, appeared to take on new proliferation, migration, and adherence capabilities in the lab, the researchers reported, hinting at a similar transformation during the development of endometriosis.
"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," Kondo and his colleagues wrote.
When mice infected with F. nucleatum received daily transvaginal treatment with the antibiotics chloramphenicol and metronidazole, they showed diminished TGF-beta and TAGLN expression, along with reduced M2 macrophage immune cell infiltration and dialed down representation of endometriotic lesions.
Kondo noted that the antibiotic metronidazole, which is already being used to treat the protozoan parasite behind sexually transmitted trichomoniasis infections, is known to have activity against Fusobacterium.
"Although further studies are needed, our data suggest that targeting Fusobacterium in the endometrium by antibiotic treatment may be a therapeutic option for patients with endometriosis," the authors concluded.