Bacterial infection may be a ‘key event’ in endometriosis, study points out

E.Endometriosis, a common gynecological disease, is one of health mimics. It can present as a variety of painful symptoms that go undetected on scans and tests. And for an estimated 10% to 15% of women with endometriosis, 10+ years to get a diagnosis.

Part of the delay is that researchers still don’t understand exactly how endometriosis develops, except that the reflux of menstrual blood through the fallopian tubes plays a role in some cases. It’s for However, growing evidence suggests that bacteria are also involved.

and study In a paper published Wednesday in the journal Science Translational Medicine, researchers at Nagoya University documented how Fusobacterium promotes the development of endometriosis.

Researchers analyzed tissue samples from 79 women with and without endometriosis who underwent surgery at Nagoya University Hospital and Toyota Kosei Hospital in Japan. They found that 64% of patients with endometriosis had Fusobacterium in their endometrium, compared with less than 10% of women in the control group. Vaginal swabs from these patients showed similar results. Patients with endometriosis had a much higher prevalence of bacteria than those without endometriosis.

The existence of Fusobacterium with double-headed pencil-like cells is not surprising. These are naturally occurring bugs that are common in the microbiome of the mouth, gut, and vaginal areas. Although Fusobacterium rarely causes serious infections, recent studies have associated Fusobacterium with certain inflammatory conditions, including: colorectal cancer and severe gum infections periodontitis.

It has been thought that the uterus is a near-sterile environment and contains far fewer bacteria than the vagina and other parts of the body. However, some studies suggest that fusobacteria are still present there and may be more prevalent in patients with endometriosis.

Yutaka Kondo and colleagues wondered how this bacterium could cause endometriosis.

Their analysis suggests that Fusobacterium infection may cause structural changes that are characteristic of endometriosis, such as the distribution of extrauterine endometrium-like tissue. “Retrograde menstruation” causes blood and tissue to drain through the fallopian tubes into the abdominal cavity. But they think the presence of the worm in endometrial cells is what causes the problem. “The key event is Fusobacterium infection,” says Dr. Kondo, a doctor and researcher in the Department of Cancer Biology, Nagoya University Graduate School of Medicine.

Fusobacterium sounds a metaphorical alarm that awakens connective tissue cells called fibroblasts to make them stickier and proliferate more.that alarm transforming growth factor betaestablished culprit of endometriosis It has the power to transform cold, undividing fibroblasts into potent transgelin (TAGLN)-positive myofibroblasts. These cells are good at regeneration and aggregation.

Certain types of Fusobacterium F. nucleatum may also trigger innate immune responses around endometriotic lesions (tissue growing outside the uterus) and produce more transforming growth factors. .

Rama Kommagani, one of the first researchers to establish a link between the microbiome and endometriosis, said the interaction between Fusobacterium and transforming growth factor beta is the most interesting part of the new paper. . “Its role in converting fibroblasts to myofibroblasts is very compelling,” said Kommagani, associate professor of pathology and immunology at Baylor College of Medicine.

Kondo and his team took their findings a step further by introducing the F. nucleatum bacterium into the uterus of mice. Importantly, although mice do not have menstrual cycles or randomly develop endometriosis, Kondo’s group was able to confirm the reach of Fusobacterium in rodents. It means that

Then they cured them. By using vaginal metronidazole and chloramphenicol, antibiotics that can kill F. nucleatum, the researchers found that from bacterial infiltration to changes in growth factors (alarm) and juiced muscle fibers. We were able to attenuate the overall ramifications of blasts and endometriotic lesions. “The data were compelling for the specific organisms they tested,” Kommagani told STAT. “But I think it should have been done in germ-free mice, which have no microbiome.” That way, researchers can watch Fusobacterium and its effects, he said.

Other studies using mice include: By Commagani Teamalso showed that metronidazole, commonly used to treat the sexually transmitted disease trichomoniasis, suppresses endometriosis.that job later led to Small, ongoing clinical trials The University of Louisville is studying the effect of metronidazole on postoperative pain after endometriosis surgery.

Kondo believes that metronidazole, also known as MZ, could be an attractive tool. “If the drug is used properly, the adverse effects are fairly limited,” he says.

However, broad-spectrum antibiotics that target vast numbers of pathogens can also have unintended effects as they also wipe out beneficial bacteria for the microbiome. “Also, in the long term, antibiotic resistance will prevent us from using antibiotics,” Commagani said.Established antibacterial resistance growing problem For decades, because bugs evolve faster and faster than humans can develop new antibiotics. For this reason, experts recommend that the drug should be used as optimally as possible for pathogens that harm humans, in case of emergency.

Antibiotics may therefore not be a permanent solution, but Kondo’s work raises the possibility that other treatments may be a permanent solution. For example, blocking the activation cascade of myofibroblasts with drugs could have significant benefits, Kommagani said. Endometriosis urgently needs treatment.

For more than half a century, endometriosis patients have taken oral contraceptives. not really helpful, due to the lack of better treatment options. The most effective strategy so far is surgery to remove excess tissue, but recurrences of endometriosis are common. If this condition is left untreated, it comes at a great price. Many report severe and unbearable cramps, painful intercourse, and infertility, among other disabling symptoms.

Researchers still don’t know exactly how Fusobacterium invades endometrial tissue and what makes some people more susceptible to infection than others. The bacterium can be sexually transmitted, but it can also be passed simply through the bloodstream through the mouth or throat to the uterus. Commagani also wants to know the mechanism by which Fusobacterium enters endometriotic lesions and activates harmful fibroblasts, as it is not clearly explained in the paper.

But new research offers insight into the causes of at least some cases of the complex condition of endometriosis.

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