Tag: endometriosis

Categories : Lab Tests and Imaging Obstetrics & GynaecologyTags :

A Potential Stool Test for Endometriosis also Suggests an IBD Link

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Promising findings by researchers at Baylor College of Medicine and collaborating institutions could lead to the development of a non-invasive stool test and a new therapy for endometriosis, a painful condition that affects nearly 200 million women worldwide. The study appeared in the journal Med.

“Endometriosis develops when lining inside the womb grows outside its normal location, for instance attached to surrounding intestine or the membrane lining the abdominal cavity. This typically causes bleeding, pain, inflammation and infertility,” said corresponding author Dr Rama Kommagani, associate professor in the Department of Pathology and Immunology at Baylor. “Generally, it takes approximately seven years to detect endometriosis and is often diagnosed incorrectly as a bowel condition. Thus, delayed diagnosis, together with the current use of invasive diagnostic procedures and ineffective treatments underscore the need for improvements in the management of endometriosis.”

“Our previous studies in mice have shown that the microbiome, the communities of bacteria living in the body, or their metabolites, the products they produce, can contribute to endometriosis progression,” Kommagani said. “In the current study, we took a closer look at the role of the microbiome in endometriosis by comparing the bacteria and metabolites present in stools of women with the condition with those of healthy women. We discovered significant differences between them.”

The findings suggested that stool metabolites found in women with endometriosis could be the basis for a non-invasive diagnostic test as well as a potential strategy to reduce disease progression.

The researchers discovered a combination of bacterial metabolites that is unique to endometriosis. Among them is the metabolite called 4-hydroxyindole. “This compound is produced by ‘good bacteria,’ but there is less of it in women with endometriosis than in women without the condition,” said first author Dr Chandni Talwar, postdoctoral associate in Kommagani’s lab.

“These findings are very exciting,” Talwar said. “There are studies in animal models of the disease that have shown specific bacterial metabolite signatures associated with endometriosis. Our study is the first to discover a unique metabolite profile linked to human endometriosis, which brings us closer to better understanding the human condition and potentially identifying better ways to manage it.”

Furthermore, extensive studies also showed that administering 4-hydroxyindole to animal models of the disease prevented the initiation and progression of endometriosis-associated inflammation and pain. 

“Interestingly, our findings also may have implications for another condition. The metabolite profile we identified in endometriosis is similar to that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions,” Kommagani said. “Our findings support a role for the microbiome in endometriosis and IBD.”

The researchers are continuing their work toward the development of a non-invasive stool test for endometriosis. They are also conducting the necessary studies to evaluate the safety and efficacy of 4-hydroxyindole as a potential treatment for this condition.

Source: Baylor College of Medicine

Categories : Lab Tests and Imaging Obstetrics & GynaecologyTags :

Investigating New Diagnostic Tools for Early Diagnosis of Endometriosis

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Endometriosis is a common, burdensome, chronic disease that affects 190 million women worldwide, and may cause life-altering consequences such as chronic pain, infertility and quality of life. Early diagnosis remains a major clinical and public health challenge. The average time to diagnose endometriosis is seven years after the onset of symptoms, which include abdominal pain and cramping before, during and after menstruation, among others.

In a commentary published in The Journal of Reproductive Medicine, Gynaecology & Obstetrics, researchers from Florida Atlantic University’s Schmidt College of Medicine and collaborators, conducted a PubMed search to identify promising approaches for early diagnosis of endometriosis.

“Currently, diagnosing endometriosis involves a thorough review of the patient’s medical history and physical examination,” said first author Panagiota “Yiota” Kitsantas, PhD, professor and chair of the Department of Population Health and Social Medicine, FAU Schmidt College of Medicine. “The most commonly used and accurate diagnostic methods are pelvic exams, abdominal ultrasound, MRI and laparoscopy. Laparoscopic surgery is considered the gold standard for diagnosing endometriosis by gynaecologists, but it can be expensive and carries potential risks of surgical complications. Moreover, the accuracy of laparoscopy can vary based on the surgeon’s experience and the stage of the disease.”

The authors say the ideal test for early diagnosis of endometriosis would be to use symptom-based criteria to determine who should undergo testing and then set optimal cut-points to maximise sensitivity and specificity. A test with high predictive value would accurately confirm endometriosis if positive and exclude it if negative. Although less ideal tests may not provide definitive results, they can be useful in reducing the number of patients who need to proceed to more invasive procedures, like laparoscopy.

Endometriosis involves hormonal imbalances that trigger angiogenesis, apoptosis, immune responses, and inflammation. Diagnostic tools for endometriosis have been developed to detect biomarkers, such as mRNA fragments in blood and saliva, but these have shown low accuracy.

“Non-invasive methods like MRI and transvaginal ultrasound are only effective for advanced stages of endometriosis,” said co-author Charles H. Hennekens, MD, professor at FAU Schmidt College of Medicine. “Recent research has focused on a novel noninvasive method of detecting myoelectric activity in the gastrointestinal tract as a potential diagnostic tool. Electroviscerography or EVG could detect unique myoelectric patterns associated with endometriosis, though this approach is promising but unproven.”

Currently, there is no FDA-approved non-invasive test for endometriosis, and further analytic studies leading to peer-reviewed publications are needed to refine these emerging technologies and establish effective diagnostic criteria.

“Early diagnosis of endometriosis remains a challenge, with a succession of promising approaches ultimately not bearing fruit thus far,” said Kitsantas. “Once new technologies such as EVG are more fully evaluated, they may give clinicians the post-test certainty they need to transition from symptom-based to diagnosis-based treatment.”

Source: Florida Atlantic University

Categories : Obstetrics & GynaecologyTags :

Researchers Create a Hydrogel Implant to Treat Endometriosis

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Researchers from ETH Zurich and Empa have developed a hydrogel implant that can help prevent endometriosis. This innovation, which is described in Advanced Materials, also acts as a contraceptive.

A hydrogel is a gel made of a type of plastic that can bind water. Hydrogels have a variety of use cases, including contact lenses, delivering doses of medication within the body, moisturisers, water storage in soil, cleaning polluted water and as gelling and thickening agents. Now, the researchers have developed the first hydrogel implant designed for use in fallopian tubes. This innovation performs two functions: one is to act as a contraceptive, the other is to prevent the recipient from developing endometriosis in the first place or to halt the spread if they do.

Around four years ago, Inge Herrmann made a new addition to her research group at the Department of Mechanical and Process Engineering at ETH and Empa. The new member was a senior physician specialising in gynaecology who was keen to pursue clinically-inspired research. This kind of interdisciplinary collaboration was an experiment for the whole team. Their initial goal had been to turn a hydrogel into a new kind of contraceptive for women. However, after the research team began talking to the gynaecologist, they realised that implanting a hydrogel to occlude the fallopian tubes could also help prevent endometriosis.

Preventing endometriosis by occluding the fallopian tubes

Around 10 percent of women suffer from endometriosis. However, it is still unclear exactly what causes this condition. The assumption is that during menstruation, blood flows back along the fallopian tubes and into the abdominal cavity. This blood contains cells from the uterine lining (endometrium), which settle in the abdominal cavity and as a result can cause inflammation, pain and the formation of scar tissue.

The researchers found a way to create a hydrogel implant capable of successfully occluding the fallopian tubes and thus preventing retrograde menstruation. “We discovered that the implant had to be made of an extremely soft gel – similar in consistency to a jelly baby – that does not impact native tissue and is not treated and rejected as a foreign body,” explains Alexandre Anthis, lead author of the study.

The hydrogel implant swells to around twice its original size when it comes into contact with liquid (arrow 1 left to centre) and can be easily and painlessly destroyed using UV light or a special solution (arrow 2 centre to right). (Graphic: adapted from Anthis AHC et al., Advanced Materials, 2024)

An advantage of hydrogels is that they swell when brought into contact with liquid. As a result, this new implant starts off at approximately 2mm in length. But once implanted in the fallopian tubes as part of a non-surgical procedure using a hysteroscope – an instrument for inspecting the uterine cavity – the implant swells to more than double its original size. The hydrogel then acts as a barrier to both sperm and blood. “Our hydrogel implant can be easily and quickly destroyed, either with UV light or a special solution, so that recipients don’t have to have an invasive and risky operation should they decide to reverse the procedure,” Herrmann says.

Source: ETH Zurich

Categories : Antibiotics Obstetrics & GynaecologyTags :

Targeting A Particular Bacteria Reduced Endometriosis Lesions

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A research group from Nagoya University in Japan has discovered that using an antibiotic to target Fusobacterium reduced the formation of lesions associated with endometriosis, a gynaecological disorder characterised by endometrial tissue growing outside of the uterus. Their findings, published in Science Translational Medicine, suggest an alternative treatment for this disorder based on antibiotics.

Endometriosis affects one in ten women between the ages of 15 and 49. The disorder can cause lifelong health problems, including pelvic pain and infertility. Although it can be treated using hormone therapy and surgical resection, these procedures sometimes lead to side effects, recurrence, and a significant impact on pregnancy.

The group led by Professor Yutaka Kondo (he, him) and Assistant Professor Ayako Muraoka (she, her) from the Nagoya University Graduate School of Medicine, in collaboration with the National Cancer Center, found that the uterus of mice infected with Fusobacterium had more and heavier lesions. However, mice that had been given an antibiotic to eradicate Fusobacterium saw improved lesion formation.

The team’s findings strongly suggest that targeting Fusobacterium is an effective non-hormonal antibiotic treatment for endometriosis. Dr Kondo praised the potential for easier diagnosis and treatment. “Eradication of this bacterium by antibiotic treatment could be an approach to treat endometriosis for women who are positive for fusobacteria infection, and such women could be easily identified by vaginal swab or uterus swab,” he said.

This study also shows the benefit of looking at upstream events to determine causative agents. The initial finding was that a protein called transgelin (TAGLN) was often upregulated in patients with endometriosis. This was unsurprising because the protein is associated with processes that are important in the development of endometriosis. However, this finding led them to determine that transforming growth factor beta (TGF-β) seemed to cause the upregulation of TAGLN. Since TGF-β is released by macrophages, the natural anti-inflammatory response and immune regulation cells of the body, this led them to conclude that these macrophages were being activated in response to Fusobacterium.

“In this study, we demonstrated that the Fusobacterium-TAGLN-endometriosis axis is frequently dysregulated in endometriosis,” said Dr Kondo. “Our data provide a strong and novel rationale for targeting Fusobacterium as a non-hormonal antibiotic-based treatment for endometriosis.”

Clinical trials of antibiotic treatment for human patients are ongoing at the Department of Obstetrics and Gynecology at Nagoya University Hospital.

Source: Nagoya University

Categories : Obstetrics & GynaecologyTags :

Endometriosis Hijacks Foetal Tolerance to Evade the Immune System

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In about 10% of women, endometrium-like tissues (known as lesions) also grow outside of the uterus, leading to endometriosis. Endometriosis is characterised by pain and can cause infertility, but its molecular mechanisms and drivers remain unknown. Now, a comprehensive study reveals how lesions escape immune surveillance, by taking advantage of mechanisms for the body tolerating a foetus during pregnancy.

Definitive diagnosis and clinical response still present significant challenges, with a common treatment being hormonal therapy with surgery. Unfortunately, surgery must be repeated if lesions recur, and they often do. To improve the situation, a better understanding of how and why the lesions grow, their cellular makeup, their microenvironments, and other aspects of their biology is essential.

The Jackson Laboratory’s (JAX) Elise Courtois, PhD, in partnership with UConn Health’s gynaecological surgeon Danielle Luciano, MD, recently completed an important study to develop a comprehensive cell atlas of the disease based on lesions obtained from 14 individuals who had treatment for endometriosis

The paper, published Nature Cell Biology, includes a thorough comparison of healthy endometrium tissue and ectopic (outside their normal site) lesions. The data also describes the endometriosis microenvironment and the conditions that allow the lesions to form and grow in what should be unhospitable regions.

“The study builds a robust foundation for a better understanding of endometriosis and how it grows,” said Dr Luciano.   “It’s exciting progress that we hope leads to earlier diagnosis and the ability to specifically target these abnormal cells for better treatments.”

The research team worked with tissues from individuals who had lesion removal at UConn Health for relief of symptoms. All were also receiving hormone therapy, the most frequent endometriosis management strategy. Not surprisingly, given that lesions are described as endometrial-like tissues growing in the wrong place, the cellular composition of the lesions in the peritoneum were quite similar to that of the normal endometrium. On the other hand, ovarian lesions had extensive differences in both composition and gene expression from the peritoneal ones. So while both ovary and peritoneum are receptive to the formation of lesions, they represent different environments and lead to important cellular and molecular differences between the two sites. The finding indicates that site-specific therapeutic design may be necessary to develop more effective treatments.

Another aspect of endometriosis is that, like cancer, the lesions represent abnormal growth that would typically be eliminated by immune surveillance. The researchers therefore investigated the immune cells in the peritoneal lesion microenvironment to see why they do not eliminate the abnormal lesion cells. They found that macrophages and dendritic cells contribute to conditions that promote immune inhibition and the promotion of immunosurveillance escape. Their specific characteristics are similar to those associated with foetal tolerance during pregnancy, which suggests that endometriosis hijacks a necessary, naturally occurring immune process to allow for lesion formation and persistence.

The paper details other aspects of both normal endometrium and ectopic lesions, including properties of vascularisation and the drivers of regeneration in endometrium and, perhaps, the formation of lesions in endometriosis. Of particular interest were key differences in the vascularisation of peritoneal versus ovarian lesions, further emphasising the site-specific nature of endometriosis. Also of note was the identification of a previously uncharacterised population of epithelial cells that may be progenitor cells for both endometrium and lesion formation, but more work is needed to define their precise role.

“Single cell analyses and hyperplexed antibody-based imaging techniques offer powerful insights into the complexity of the endometriosis microenvironment,” said Dr Courtois. “Understanding this complexity will be key for developing the new, efficient diagnostic and therapeutic tools that are so badly needed.”

Overall, the data captures a full description of endometrium and lesions, laying a strong foundation for understanding the vital cellular players and molecular dynamics of the disease. The data represents an important step forward for research into endometriosis and provides essential information for future therapeutics and diagnostics that can provide relief for those with this under-investigated disease.

Source: University of Connecticut