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Gut microbiota predict endometriosis better than vaginal microbiota.
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Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (BOT), Low Nickel Diet, and Metronidazole therapy.
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Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Endometriosis affects about 10-15% of women globally, causing chronic pelvic pain, infertility, and other severe symptoms. [1] While experts often point to retrograde menstruation as the cause of endometriosis, this theory falls short because it fails to explain why many women with retrograde menstruation never develop endometriosis, nor does it account for cases in prepubertal girls, postmenopausal women, men, or endometriotic lesions found in locations far from the pelvis, such as the lungs. [2] This clearly indicates that other significant pathophysiological factors are involved. The lack of a definitive cure and the suboptimal effects of current treatments highlight the urgent need for a breakthrough.
While endometriosis primarily affects the endometrium, it can have systemic effects and influence various aspects of a person’s health. Individuals with endometriosis may be at an increased risk for other conditions. These include chronic pelvic pain, infertility, irritable bowel syndrome (IBS), interstitial cystitis, autoimmune conditions, and ovarian cancer. [3][4] Researchers have also documented that many of these comorbidities involve urogenital or gut dysbiosis, suggesting potential microbiome signature overlaps between the conditions. [5]
Prevailing causal theories of endometriosis—such as retrograde menstruation, Müllerianosis, and lymphovascular metastasis—provide foundational insights but fall short of fully explaining the condition’s complexity. A more comprehensive, systems-based approach that integrates these theories with emerging insights—such as the role of the microbiome and the microbial metallomics theory of endometriosis—offers a more nuanced and integrated understanding of the disease. By challenging entrenched assumptions and embracing granular, data-driven perspectives, we can identify previously overlooked mechanisms driving pathogenesis. This shift not only enriches our understanding of endometriosis but also paves the way for highly personalized treatments that leverage microbiome research, dramatically improving patient outcomes and redefining the standard of care.
| Theory | Limitations / Criticisms |
|---|---|
Retrograde Menstruation Theory | While widely accepted, the retrograde menstruation theory does not explain why retrograde menstruation occurs in many women, but only a subset develop endometriosis. It also fails to account for cases in individuals without menstrual cycles, such as prepubertal girls [6], postmenopausal women [7], men [8], and in locations far from the pelvis, such as the lungs. [9] |
Environmental Theory | Direct causal links between environmental toxins and endometriosis are difficult to establish, and the environmental theory of endometriosis cannot fully explain hereditary patterns and internal physiological changes associated with the disease. [10] |
Coelomic Metaplasia Theory | The coelomic metaplasia theory does not fully explain the occurrence of endometriosis in distant sites, such as the lungs or brain, where the peritoneal lining is not present. [11][12] Endometriotic lesions are heterogeneous in nature, varying in location, morphology, and biological behavior. The coelomic metaplasia theory does not fully account for this heterogeneity, which might be better explained by a multifactorial model involving various pathogenic processes.[13] |
Müllerianosis Theory | The Müllerianosis theory struggles to explain isolated occurrences of endometriosis in males or areas unrelated to the embryonic development of the Müllerian ducts, such as the spinal cord [14] or skeletal muscular system [15], suggesting that additional factors must be involved in disease manifestation. |
Genetic and Epigenetic Theory | The genetic and epigenetic theory of endometriosis proposes that genetic predisposition and epigenetic modifications significantly influence susceptibility to endometriosis. While genetics play a role, this theory does not account for environmental and acquired aspects of the disease, and specific genetic markers with high predictive value have yet to be identified. [16] |
Lymphovascular Metastasis Theory | The lack of consistent evidence for endometrial cell survival and growth in distant systems challenges the lymphovascular metastasis theory, and it does not address the origin of endometriosis in areas not served by the lymphovascular network. |
| Microbiome Theory | It is unclear whether dysbiosis is a cause or consequence of endometriosis, and the specific mechanisms by which microbiome alterations contribute to it remain to be fully elucidated. Nonetheless, the microbiome theory of endometriosis is likely to play a significant role in the development of therapies based on recent research findings. |
| Microbial Metallomics Theory of Endometriosis | While this model uniquely integrates genetics, environmental factors, the microbiome, and immune function into a cohesive framework with translational potential, the Microbial Metallomics Theory of Endometriosis requires further empirical validation. Additional clinical studies are needed to clarify whether microbial metallomics is a primary driver of endometriosis or a contributing factor to its progression. |
Laparoscopy remains the gold standard for diagnosing endometriosis. Despite its accuracy, laparoscopy is still an invasive procedure with associated risks and costs, necessitating the development of less invasive diagnostic tools. As researchers and clinicians increasingly leverage microbiome signatures and metabolomic signatures for non-invasive diagnostic purposes and treatment guidance, these tools are more likely to become mainstream in medical practice.[17][18] Their growing utility in providing earlier, more accurate diagnoses and tailoring targeted therapies underscores their potential to revolutionize non-invasive diagnostics, particularly in conditions like endometriosis.[19]
The interplay between metal homeostasis, estrogen metabolism, and metabolomic disruptions in endometriosis reveals how systemic and localized factors converge to drive endometriosis progression. These interrelationships underscore the microbiome’s central role in the disease’s pathogenesis and highlight opportunities for microbiome-based diagnostics and microbiome-targeted interventions (MBTIs).
High iron levels from retrograde menstruation promote pathogenic bacteria, lesion growth, inflammation, and oxidative stress.[20] Studies suggest that nickel sensitivity affects 90.3% of patients, or possibly even more[21], and that a low-nickel diet shows significant clinical benefits. [22] Zinc, despite its antioxidative and anti-inflammatory role, has been significantly associated with an increased risk of endometriosis owing to the activity of matrix metalloproteinases which are implicated in endometriotic lesion invasion.[23]Metalloestrogens like cadmium, nickel, and lead increase oxidative stress, inflammation, and estrogenic activity. [24] These findings highlight the role that the metallomic signature plays in the condition, and potential of chelation therapies, dietary modifications, and reduced heavy metal exposure for managing or preventing endometriosis.
Iron
Systematic reviews confirm that iron levels are abnormally high in endometriosis lesions, where iron chelation therapy has shown efficacy in alleviating symptoms and slowing disease progression.[26] High iron content stems from repeated episodes of retrograde menstruation, during which red blood cells break down, releasing iron into the pelvic cavity. This excess iron disrupts homeostasis, driving inflammation and oxidative stress, which support the growth of endometriotic lesions. Furthermore, pathogenic bacterial species associated with endometriosis exhibit robust iron acquisition mechanisms, indicating that iron dysregulation also influences microbial dynamics in the pelvic environment. [27]
Nickel
Nickel allergy has been identified as a risk factor for endometriosis, and elevated nickel levels in the blood have been suggested as a causal factor in endometriosis development, with 90.3% of women experiencing allergic contact mucositis (ACM). [28][29] Nickel’s classification as a metalloestrogen highlights its estrogen-mimicking capabilities, contributing to hormonal dysregulation in endometriosis. [30] Women with nickel sensitivity frequently report gastrointestinal symptoms overlapping with irritable bowel syndrome (IBS). Positive nickel oral mucosa patch tests (omPT) further validate this connection. [32] Screening for nickel sensitivity in endometriosis patients with gastrointestinal symptoms and recommending a low-nickel diet are key considerations for personalized treatment strategies.
Cadmium
Cadmium is a metalloestrogen that mimics estrogen by binding to estrogen receptors, potentially contributing to the pathogenesis of endometriosis, an estrogen-dependent disease. [33] Research has linked cadmium exposure to oxidative stress, which plays a significant role in the development of endometriosis. By inducing the formation of reactive oxygen species (ROS) and impairing antioxidant defenses, cadmium exacerbates oxidative damage to cellular components, including DNA and proteins. However, findings regarding cadmium’s direct association with endometriosis remain inconsistent. While some studies report elevated cadmium levels in women with endometriosis, others find no significant difference. A systematic review has highlighted the need for more robust investigations to determine cadmium’s precise role. The potential synergistic effects of cadmium with other heavy metals, such as lead, may amplify its impact on oxidative stress and disease progression. [34][35]
Lead
Lead exposure is also implicated in the pathogenesis of endometriosis through its oxidative and endocrine-disrupting effects. Studies have shown a significant association between blood lead levels (BLLs) and the prevalence of endometriosis, with even low levels (<5 µg dl) contributing to increased risk. furthermore, lead exposure appears have a synergistic effect when combined with cadmium, amplifying oxidative stress and potentially accelerating disease progression. occupational particularly in industrial settings, has been associated hospitalization rates for endometriosis. [36][37][38]
Zinc
Higher dietary zinc intake has been significantly associated with an increased risk of endometriosis, with women consuming over 14 mg/day showing a 60% greater likelihood of the condition compared to those consuming ≤8 mg/day (adjusted odds ratio: 1.60, 95% CI: 1.12–2.27, p = 0.009). Zinc, despite its antioxidative and anti-inflammatory roles, may have a counterproductive effect when consumed in excess, potentially influencing immune modulation, oxidative stress, and the activity of matrix metalloproteinases (MMP-2 and MMP-9), which are implicated in endometriotic lesion invasion. [39]
Several nutritional immunity factors are found to be elevated in endometriosis. Studies suggest that levels of lactoferrin are significantly increased in individuals with endometriosis, reflecting a heightened immune response. [40] The increased levels of these proteins indicate an attempt by the body to sequester nutrients and metals from pathogens, while also modulating the inflammatory environment associated with endometriosis. This suggests that understanding the role of nutritional immunity could provide insights into the management and treatment of endometriosis.
The estrobolome, a subset of gut microbiome genes, regulates estrogen metabolism and plays a critical role in endometriosis progression. Major microbial associations (MMAs) in the endometriosis microbiome signature, such as Escherichia coli, Bacteroides fragilis, and Streptococcus agalactiae produce β-glucuronidase, increasing estrogen deconjugation and circulating hormone levels. This microbial activity drives inflammation, angiogenesis, hormonal dysregulation, and cellular changes, contributing to endometriosis pathogenesis. Dysbiosis in endometriosis is both a cause and consequence of the disease. [41][42][43]
Our validation method confirms microbiome-targeted interventions (MBTIs) by aligning therapeutic effects on microbial imbalances with clinical outcomes, key pathological markers, and major microbial associations (MMAs) of endometriosis. This dual approach ensures that interventions address both dysbiosis and the condition’s core biological mechanisms, reinforcing the accuracy of microbiome signatures and the efficacy of MBTIs. Promising candidates with partial alignment or preliminary benefits are also identified for further research, ensuring a pipeline of innovative therapies for future validation.
| Intervention | Classification | MBTI Status |
| Pueraria flower extract (PFE) | Herbal | Validated |
| Metronidazole | Pharmaceutical | Validated |
| Metformin | Drug Repurposing | Validated |
| Low-Nickel Diet | Diet | Validated |
| Hyperbaric Oxygen Therapy (HBOT) | Biophysical Interventions | Promising Candidate |
| Microbiome Diet for Endometriosis | Diet | Promising Candidate |
| Lactoferrin | Supplement |
| Axitinib, Afatinib, Linifanib | Drug Repurposing | Drugs like Axitinib, Afatinib, and Linifanib, known for their anti-angiogenic effects inhibit the growth of blood vessels that sustain ectopic endometrial tissue. By reducing angiogenesis, these drugs, or similar VEGFR / PDGFR / EGFR/ HER2 inhibitors may help reduce symptoms of endometriosis. [31] |
| 3D printed pirfenidone ovules | Drug Repurposing | Pirfenidone, used against idiopathic pulmonary fibrosis, shows promise in endometriosis treatment due to its anti-fibrotic properties. Studies are exploring 3D-printed vaginal ovules for its delivery. These ovules offer controlled release, higher efficacy, and fewer side effects. [32] |
| Transvaginal Photobiomodulation | Biophysical Intervention | Transvaginal photobiomodulation reduced inflammation and improved pain in endometriosis study participants. [33] |
| Vaginal Microbiome Transplant (VMT) | Microbiome Restoration | An animal model study investigating the efficacy of antibiotics and VMT for endometriosis found that both modalities were effective, and reduced disease progression via the NF-κB Signaling Pathway. [34] |
| Fecal Transplant (FMT) | Microbiome Restoration | As of now, there are no clinical trials or peer-reviewed studies specifically evaluating FMT as a treatment for endometriosis. Nonetheless, several reviews have speculated that it would be an effective treatment option based on the emerging understanding of the gut microbiome’s role in the condition. [35, 36, 37, 38] |
| Low Trans-unsaturated fatty acids and red meat diet | Diet | Trans-unsaturated fatty acids and red meat are associated with an increased risk of developing endometriosis. [40] |
| Fruits, vegetables, dairy products, and omega-3 fatty acids | Diet | Women who consume a large amount of fruits, vegetables, dairy products, and omega-3 fatty acids have an attenuated risk of endometriosis. [41] |
| Omega-3 polyunsaturated fatty acids | Diet | Found to attenuate inflammation in endometriosis models [42]; high intake correlated with a lower risk of endometriosis development. [43] |
| Mediterranean Diet | Diet | A study found that Mediterranean Diet adherence impacts the endometrial environment, suggesting diet modifications could enhance fertility. [45] |
| Increased Fruit intake, particularly citrus, decreased vegetable intake, particularly cruciferous vegetables. | Diet | Higher fruit intake, especially citrus fruits, was inversely associated with laparoscopically confirmed endometriosis, suggesting a protective effect potentially linked to beta-cryptoxanthin. In contrast, cruciferous vegetables were linked to increased risk, highlighting the complex interplay between diet and endometriosis risk factors. [54] |
| Hexane extract of Aged Black Garlic | Supplement | The research on aged black garlic, specifically its hexane extract (HEABG), shows significant promise for endometriosis treatment. HEABG inhibits cell proliferation and cell cycle progression in TNF-α-activated human endometriotic stromal cells. This action occurs through the suppression of the ERK and JNK signaling pathways [50]. Additionally, HEABG reduces TNF-α-induced expression of ICAM-1 and VCAM-1 by inhibiting NF-κB and AP-1[51]. These mechanisms could decrease immune cell recruitment to lesions, potentially reducing disease-related inflammation. These findings position aged black garlic, particularly its hexane extract, as a promising candidate for further research in endometriosis treatment. The antioxidant, anti-cancer, and pro-apoptotic properties of aged black garlic extracts have been noted in various studies, contributing to a growing body of evidence supporting its therapeutic potential in a range of pathologies [52]. |
| Resveratrol | Supplement | The potential therapeutic effects and molecular mechanisms of resveratrol on endometriosis are primarily due to its anti-inflammatory, anti-proliferative, anti-angiogenic, and antioxidative properties [53]. Several studies have demonstrated that resveratrol can inhibit the growth and angiogenesis (formation of new blood vessels) of endometrial tissue, which is a key factor in the development of endometriosis. It has been observed that resveratrol supplementation in animal models of endometriosis resulted in a decrease in the number and volume of endometrial implants, as well as a suppression of proliferation, vascularization, and inflammation in these implants. [54] Furthermore, resveratrol has been shown to increase apoptosis (programmed cell death) in endometriotic cells and reduce their invasiveness. This suggests that resveratrol could potentially alter the cellular mechanisms that drive the progression of endometriosis. [55]. |
| Catechins (green tea) | Supplement | Catechins, particularly epigallocatechin-3-gallate (EGCG) from green tea, show beneficial effects for endometriosis. EGCG inhibits angiogenesis, crucial for endometriosis growth. It has been found to reduce lesion size and angiogenesis in experimental models. EGCG also induces apoptosis and modulates inflammatory responses in lesions [x, x] . |
| Curcumin | Supplement | Curcumin, from turmeric, exhibits potential in endometriosis treatment through its multi-targeted actions. It inhibits the growth of endometriosis cells and decreases VEGF expression, affecting cell survival pathways. Curcumin’s broad spectrum of anti-inflammatory and anti-angiogenic properties makes it a candidate for further research in endometriosis management [x]. |
| Uncaria tomentosa | Supplement | Uncaria tomentosa shows promise due to its anti-inflammatory and anti-angiogenic properties. In animal studies, Uncaria tomentosa extract reduced endometriotic lesion size [x]. |
| Açai extract (Euterpe oleracea) | Supplement | Açai extract is renowned for its strong antioxidant, anti-inflammatory, and anticancer properties. These benefits largely stem from its rich polyphenol content, especially anthocyanins. Research supports Açai extract’s effectiveness in both in vivo and in vitro settings, as it suppresses the growth and survival of endometriotic lesions and reduces their size. This suggests a new strategy for managing endometriosis by targeting key pro-inflammatory and pro-angiogenic markers and influencing macrophage viability [x] . |
| European cranberry bush (Viburnum opulus) | Supplement | Research shows that Viburnum opulus extract decreases the size of endometriotic lesions. It achieves this by lowering TNF-α, VEGF, and IL-6 levels. Thus, Viburnum opulus may disrupt inflammatory and angiogenic pathways involved in endometriosis development and progression. The reduction in these biomarkers indicates that Viburnum opulus could regulate the inflammatory environment associated with endometriosis. This regulation might reduce lesion size and ease symptoms. Studies highlight that fruit extracts of V. opulus, especially EtOAc and MeOH extracts, show significant therapeutic potential in treating endometriosis. The presence of chlorogenic acid and other phenolic compounds may enhance this potential. This research supports the traditional use of V. opulus in treating gynecological conditions [x]. |
| Milk thistle (Silybum marianum) | Supplement | Silymarin significantly inhibits the establishment and growth of endometriotic lesions. It mediates its effects by downregulating crucial factors such as GDNF, its receptor gfrα1, Bcl-6b, and Bcl-2. These factors are involved in cell survival, proliferation, and neurotrophic support. Thus, silymarin may inhibit lesion growth by promoting apoptosis and inhibiting proliferation. Additionally, an increase in ERK1/2 expression indicates silymarin’s role in activating apoptotic pathways. Silymarin treatment also results in decreased angiogenesis and increased fibrosis. This suggests it may limit lesion nourishment and promote lesion regression. Therefore, silymarin offers a potentially comprehensive approach to managing endometriosis by affecting several key pathological processes [x]. |
| Calligonum comosum | Supplement | In both in vitro and in vivo studies, Calligonum comosum reduces the size of endometriotic lesions. It accomplishes this through its anti-inflammatory and anti-proliferative properties. The plant decreases vascularization by inhibiting angiogenesis, reducing the nutrient supply to lesions and alleviating pain. Moreover, it curbs the proliferation of endometrial cells by targeting cell growth pathways, thus reducing hyperplasia in lesions. Additionally, it lessens immune cell infiltration in lesions, easing inflammation and discomfort. These findings highlight its potential in reducing endometriotic lesion size, vascularization, cell proliferation, and immune cell infiltration [x]. |
| Frankincense (Boswellia serrata) | Supplement | Frankincense alleviates endometriosis by inducing apoptosis and reducing cell adhesion [x]. Its oils exhibit synergistic, additive, and non-interactive properties against various microorganisms. Specifically, Cryptococcus neoformans and Pseudomonas aeruginosa show high susceptibility to these oils [x]. |
| Melatonin | Supplement | Evidence shows that exogenous melatonin can suppress ectopic lesions, alleviate pelvic pain, and improve sleep quality in women with endometriosis, underscoring its multifaceted role in managing both the symptoms and underlying aspects of the condition [x]. Other studies found that melatonin could prevent and treat endometriosis by reducing the size and weight of the endometriotic lesions [x]. Melatonin has also been shown to reduce the Firmicutes/Bacteroidetes ratio [x], which is increased in endometriosis patients relative to healthy controls [x]. |
| Vitamin D | Supplement | Malondialdehyde level is commonly known as a marker of oxidative stress and antioxidant status [x]. Studies have found a higher level of MDA in the serum of women with endometriosis relative to healthy controls [x]. Systematic reviews have confirmed that Vitamin D supplementation significantly reduces MDA [X] Some studies have found that vitamin D supplementation significantly decreased pelvic pain and c-reactive protein scores [x], while other studies found that vitamin D treatment did not have a significant effect in reducing dysmenorrhea and/or pelvic pain [x]. |
| NAC (N-Acetylcysteine) | Supplement | Oral supplementation with NAC improves endometriosis-related pain and appears to improve fertility in patients with endometriosis.[x] |
| Probiotics | Supplement | Probiotics and prebiotics have shown potential in optimizing, maintaining, and restoring vaginal microflora, offering alternative approaches to reduce vaginal infections and promote overall female health. [x] |
| Prebiotics | Supplement | Research suggests that abnormal gut microbiota impacts female reproductive system diseases, particularly through dysbiosis-induced hypoestrogenemia, using endometriosis and its potential malignancy progression linked to genetic mutations as examples. It suggests that modifying gut microbiota with prebiotics and probiotics could help prevent and treat hormone-related gynecological diseases. [x] |
| Quercetin | Supplement | Quercetin, a flavonol, may help manage the disease by modulating estrogen activity, reducing inflammation, suppressing angiogenesis, and promoting apoptosis in endometrial cells. [x] |
| Indole-3-carbinol | Supplement | Indole-3-Carbinol significantly inhibits both the growth and vascularization of endometriotic lesions without causing adverse effects on reproductive organs. Specifically, I3C reduced the number of proliferating stromal and endothelial cells within the lesions and downregulated the expression of key pro-angiogenic molecules such as vascular endothelial growth factor receptor-2 (VEGFR2), phosphoinositide 3-kinase (PI3K), and phosphorylated extracellular signal-regulated kinase (pERK). These results suggest that I3C may interfere with angiogenic and proliferative pathways essential for the development of endometriotic lesions. [x] |
| deferoxamine, deferiprone, and deferasirox | Pharmaceutical | Studies have found that there is excess iron in the peritoneal cavity due to recurrent bleeding from endometrial lesions [x]. This excess iron provides pathogens with the necessary ions for biofilm formation and virulence factors, while other studies have found that excess iron has a deleterious effect on Lactobacillus spp [x]. Microbial iron chelators are being explored as a novel approach to developing innovative antimicrobials, with siderophore-mimicking antibiotics emerging as a targeted strategy against pathogens. These compounds have shown effectiveness against antibiotic-resistant Gram-negative bacteria, highlighting their potential in combating tough microbial challenges. Beyond their antimicrobial applications, iron chelators are also being studied for their utility in treating iron overload diseases and as potent agents in cancer therapy. This multifaceted use of iron chelators underscores their significant potential across various medical fields, including endometriosis [x]. Further, in vivo experiments show that the iron chelator deferoxamine reduced the implant size in experimental endometriosis [x]. |
| Lactoferrin | Supplement | Research on prebiotics that specifically improve the population of Lactobacillus in the female reproductive tract is limited. However, a study highlighted in the PubMed article “Antimicrobial and Prebiotic Activity of Lactoferrin in the Female Reproductive Tract: A Comprehensive Review” suggests that lactoferrin, a protein found in milk and other secretions, may have prebiotic activities.Lactoferrin can potentially support the growth of beneficial bacteria like Lactobacillus in the female reproductive tract, contributing to its health. This indicates that lactoferrin might play a role in maintaining a healthy balance of microbiota in the genital tract, and could prove useful in the treatment of endometriosis [x] |
| Gallium | Biochemical Chelation | Gallium as an iron mimic, disrupting bacterial iron metabolism when taken up instead of iron [x]. Effective in reducing bacterial load and inflammation. Shown to reduce P. aeruginosa lung infections in cystic fibrosis models in vivo. Gallium, a trivalent metal, functions as an iron mimic, disrupting bacterial iron metabolism when incorporated in place of iron. This disruption impairs essential processes such as DNA synthesis and respiration, leading to bacterial growth inhibition and cell death. Studies have demonstrated gallium’s efficacy in reducing bacterial load and inflammation, particularly against Pseudomonas aeruginosa, a common pathogen in cystic fibrosis (CF) lung infections. In vivo experiments have shown that gallium can inhibit P. aeruginosa growth and biofilm formation, making it a promising candidate for treating chronic lung infections in CF patients. [x] Additionally, gallium has been evaluated in clinical settings. A phase I clinical trial involving individuals with CF and chronic P. aeruginosa airway infections indicated that gallium administration was safe and achieved concentrations sufficient to inhibit bacterial growth. AAAS These findings suggest that gallium-based therapies could offer a novel approach to managing persistent bacterial infections, especially in cases where traditional antibiotics are ineffective due to resistance or biofilm formation. |
| Local pH Modification with lactic acid suppositories | Environmental Modification | While the importance of breathable fabrics like cotton for maintaining vaginal health is often highlighted in health advice and articles, there is a gap in clinical research directly linking the type of underwear fabric to specific reproductive health outcomes. This suggests an area for future research to provide more evidence-based guidance. Nonetheless, there is interaction between different types of bacteria and various fabric materials. Studies have shown that bacteria implicated in the etiology of endometriosis, specifically Staphylococcus aureus and Staphylococcus epidermidis, demonstrated increased adherence to fabrics as the content of polyester fibers in the fabrics increased [x]. Understanding these dynamics is crucial, particularly in relation to female reproductive health and infection control. The findings highlight that the material composition of fabrics can influence bacterial adherence, which could have implications for infection prevention strategies. |
| Oral Sex | Behavioral-Physiological Modulation | Research suggests that women who reported engaging in oral sex were less likely to have endometritis, a condition associated with Pelvic Inflammatory Disease (PID). Although endometritis is distinctly different from endometriosis, the study proposes that oral sex could stimulate an effective immune response in the genital tract, possibly due to antigenic priming of the lymphatic system, which is abundant in the oropharynx. This hypothesis, however, requires further investigation for validation [x]. |
| Sexual activity, orgasm, and tampon use during menstruation | Behavioral-Physiological Modulation | Sexual activity, orgasm, and tampon use during menstruation protect against endometriosis. [x] |
| Cotton undergarments | Behavioral-Physiological Modulation | While the importance of breathable fabrics like cotton for maintaining vaginal health is often highlighted in health advice and articles, there is a gap in clinical research directly linking the type of underwear fabric to specific reproductive health outcomes. This suggests an area for future research to provide more evidence-based guidance. Nonetheless, there is interaction between different types of bacteria and various fabric materials. Studies have shown that bacteria implicated in the etiology of endometriosis, specifically Staphylococcus aureus and Staphylococcus epidermidis, demonstrated increased adherence to fabrics as the content of polyester fibers in the fabrics increased [x]. Understanding these dynamics is crucial, particularly in relation to female reproductive health and infection control. The findings highlight that the material composition of fabrics can influence bacterial adherence, which could have implications for infection prevention strategies. |
| Dimethylglyoxime (DMG) | Biochemical Chelation | Given that nickel can have estrogenic effects and considering the high prevalence of nickel sensitivity in individuals with endometriosis, as suggested by studies indicating the improvement of symptoms following a low-nickel diet, DMG could theoretically mitigate some of the estrogen-mediated processes in endometriosis by chelating nickel. This would be particularly relevant if nickel is contributing to the disease’s severity or symptomatology through its estrogenic properties.While specific studies in the context of endometriosis are lacking, research on DMG’s bacteriostatic action in other contexts can provide a theoretical basis [x]. |
| Zeolite | Biochemical Chelation | Clinoptilolite zeolite, known for its ability to chelate several heavy metals such as nickel, has shown promising benefits for reproductive health, particularly in animal studies. By binding to nickel, zeolite can inhibit the activity of pathogens that rely on this metal as a cofactor for enzymes crucial to their survival, biofilm formation, and virulence, thereby reducing inflammation and promoting a healthier microbial balance. Beyond its antimicrobial effects, zeolite acts as a detoxifying agent, antioxidant, and immunostimulant, which helps manage oxidative stress and enhance energy levels during the postpartum period. These combined effects support the recovery of the reproductive system after birth, creating a more favorable environment for subsequent fertility and demonstrating its potential as a microbiome-targeted intervention. [x] |
| D-Chiro Inositol | Supplement | D-Chiro Inositol’s ability to reduce the development of endometriotic lesions in a mouse model suggests a therapeutic potential for this compound in the treatment of endometriosis. This finding is noteworthy because it opens a new avenue for non-hormonal treatment options, which can be particularly beneficial for patients who are unable to use hormonal therapies due to side effects or other contraindications [x]. |
| Phage Cocktail Therapy | Microbiome Restoration | Phage cocktails, compared to monophage therapy, are often employed to treat individual and multi-bacterial infections due to their enhanced efficacy in preventing bacterial resistance. When multiple phages are used simultaneously, as in a cocktail, the diverse mechanisms of action and target specificities reduce the likelihood that bacteria will develop resistance. This approach capitalizes on the various ways different phages attack bacteria, making it more challenging for bacterial populations to adapt and survive. Consequently, phage cocktails can be a more robust strategy against bacterial infections, particularly in scenarios where resistance to conventional antibiotics is a concern [x] Phage cocktails that target the specific microbiome signature of endometriosis would present major benefits for more advanced stages of endometriosis. |
| Ceylon Cinnamon Oil | Supplement | While Ceylon cinnamon may be used in traditional or alternative treatments for endometriosis, its effectiveness has not been confirmed in clinical trials. Nonetheless, Ceylon cinnamon oil does have activity against pathogens consistent with the Microbiome Signature of Endometriosis. Cinnamomum zeylanicum (CZ-EO) essential oil showed moderate activity against Fusobacterium nucleatum and Streptococcus mutans. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for Fusobacterium nucleatum were both found to be 125 μg/mL, while for Streptococcus mutans, the MIC was 200 μg/mL and the MBC was 400 μg/mL [x] . |
| Asparagus racemosus | Supplement | Asparagus racemosus Asparagus racemosus has demonstrated considerable antibacterial efficacy against various pathogenic bacteria. In a study, different concentrations of the methanol extract of Asparagus racemosus roots were tested and found to be effective against a range of bacteria implicated in the pathogenesis of endometriosis, including Escherichia coli, Shigella dysenteriae, Shigella sonnei, Shigella flexneri, Vibrio cholerae, Salmonella typhi, Salmonella typhimurium, Pseudomonas putida, Bacillus subtilis, and Staphylococcus aureus. [x] . |
| Trichostatin A | Drug Repurposing | Trichostatin A is a hydroxamic acid produced by S. hygroscopicus. Wu et al. published three studies showing that trichostatin A (TSA) reduces invasiveness and reactivates E-cadherin in endometriotic cell lines, upregulates PPARγ expression, and inhibits NF-κB activation. Seo et al. found that TSA induces apoptosis and NSAID-activated gene-1 expression in endometriotic stromal cells. Lu et al. demonstrated that TSA reduced lesion size, improved pain response, and lowered neural marker expression in a rat model. Collectively, TSA shows promise as a histone deacetylase inhibitor (HDACI) for endometriosis treatment.[61] Trichostatin A chelates zinc ions in the active site of histone deacetylases, preventing histone unpacking so DNA is less available for transcription. TSA remains one of the most potent HDAC inhibitors available. [62] |
A STOP (Suggested Termination Of Practice) recommends discontinuing medical interventions shown to be ineffective, harmful, or counterproductive based on emerging evidence. In endometriosis, heavy menstrual bleeding often leads to iron-deficiency anemia, traditionally treated with iron supplementation. However, iron supports bacteria linked to endometriosis, and iron supplementation is associated with increasing adverse effects. [x] Paradoxically, iron chelation therapies may improve absorption while reducing inflammation, highlighting the need to re-evaluate traditional practices. This illustrates how STOPs advance evidence-based care by addressing outdated or counterproductive treatments.
| STOPs | SWAPs |
| Iron Supplementation: Meta-analyses confirm that iron supplementation with ferrous sulfate is associated with a significant increase in gastrointestinal-specific side effects [x]. Iron deposits found in endometriotic lesions promote further lesion development, suggesting that iron supplementation could aggravate the disease. We are not alone in sounding the alarm on iron supplementation practices, as hypotheses from other studies suggest that iron supplementation could potentially exacerbate infection risks.[x] The mechanistic role of iron acquisition by pathogens involved in endometriosis challenges current iron supplementation practices. | Lactoferrin |
| Zinc Supplementation: Higher dietary zinc intake has been significantly associated with an increased risk of endometriosis, with women consuming over 14 mg/day showing a 60% greater likelihood of the condition compared to those consuming ≤8 mg/day (adjusted odds ratio: 1.60, 95% CI: 1.12–2.27, p = 0.009). Zinc, despite its antioxidative and anti-inflammatory roles, may have a counterproductive effect when consumed in excess, potentially influencing immune modulation, oxidative stress, and the activity of matrix metalloproteinases (MMP-2 and MMP-9), which are implicated in endometriotic lesion invasion. [63][x] These findings underscore the need for cautious zinc supplementation and further research to confirm causality and refine dietary recommendations. | |
| Gonadotropin-releasing hormone agonist (GnRHa): Because GnRHa causes anovulation and amenorrhea, GnRHa are used to treat endometriosis [x]. However, a case-controlled molecular study on 32 women, half with endometriosis and half without, investigated microbial colonization in the intrauterine environment and ovarian cystic fluid. 16S metagenome assay indicated that the proportion of Lactobacillacae was significantly decreased (p<0.01) and of Streptococcaceae, Staphylococaceae, and Enterobacteriaceae was significantly increased (p<0.05 for each) in GnRHa-treated women with endometriosis than in GnRHa-untreated women. The study suggests GnRHa treatment might actually promote sub-clinical infections in the intrauterine and ovarian environments. [x] Other studies investigating the long-term effects of GnRHa with and without hormone replacement therapy on bone mineral density in women with endometriosis found that long-term use of GnRH agonists results in a reduction in bone mineral density at the lumbar spine and hip. This reduction was not fully recovered even up to six years post-treatment. The study also found that the inclusion of hormone replacement therapy (HRT) did not significantly influence bone mineral density when compared to those who did not receive HRT. The results also demonstrated a considerable range of individual variability in BMD response among the participants, suggesting that the effects of GnRH agonists on BMD can vary significantly among different women. | Hormone Replacement Therapy [x] |
| Cruciferous Vegetables: The consumption of cruciferous vegetables is associated with an increased risk of endometriosis. [64] | Citrus Fruit |
We should probably be targeting both, even though recent studies found that vaginal microbiota may not be as important as the gut microbiota for the predictive value in endometriosis. [x] However, looking at the microbiome signature of IBD for more gut-specific microbiome targets will likely result in better treatment strategies since it is commonly associated with endometriosis.
Consider that estrogen appears to mediate the microbiome as much as the microbiome mediates estrogen. [x]
Diet is a key modulator of the microbiome, with different dietary patterns influencing microbial composition and function. While a low-nickel diet alone can have a substantial impact, additional interventions such as probiotics, prebiotics, VMT and FMT may be necessary to achieve specific therapeutic outcomes, especially in cases of severe dysbiosis or comorbid conditions, such as IBD.
Yes, microbiome-targeted interventions could be a promising alternative for patients concerned about fertility, as they do not rely on hormonal suppression, which can affect ovulation and fertility. By focusing on modulating the microbiome to reduce inflammation and pain, MBTIs may help manage endometriosis symptoms while preserving reproductive potential, making them an attractive option for those planning pregnancy or seeking non-hormonal management strategies.
Personalized microbiome therapies are tailored to an individual’s unique microbiome profile, taking into account their specific microbial composition, genetics, diet, and lifestyle. This approach contrasts with conventional treatments, which often take a one-size-fits-all approach. Personalized therapies aim for higher efficacy and fewer side effects by targeting the unique microbiome-related needs of each patient.
Effectiveness can be assessed through various methods, including monitoring clinical outcomes, changes in microbiome composition through sequencing technologies, biomarkers of inflammation or disease, and patient-reported outcomes. Regular follow-ups and adjustments to the intervention may be necessary based on these assessments to optimize therapeutic benefits.
To integrate microbiome signatures into routine clinical practice, advancements in standardized methodologies for microbiome sampling, data analysis, and interpretation are needed. Additionally, more large-scale, longitudinal studies are required to establish robust, clinically relevant microbiome biomarkers and validate them across diverse populations and conditions.
This study reveals Anaerococcus as a predictive marker for endometriosis severity and highlights Lactobacillus crispatus’s lactic acid-mediated modulatory role, offering promise for non-invasive diagnostics.
This pilot observational cross-sectional study investigated the vaginal and gut microbiome profiles in women with and without endometriosis to evaluate their potential as less invasive diagnostic tools for the disease. Researchers analyzed microbiome samples collected during two menstrual cycle phases—follicular and menstrual—from 35 women with endometriosis and 24 controls. They further explored the microbiome's association with disease severity, categorized by rASRM (revised American Society for Reproductive Medicine) stages, using 16S rRNA sequencing and machine learning models.
The study included 59 women aged 21–49, with 35 participants having surgically confirmed endometriosis and 24 serving as controls. Participants were excluded if they had a history of autoimmune diseases, active infections, or recent use of antibiotics or hormones. Vaginal and rectal samples were obtained from all subjects to evaluate microbial community state types (CSTs) and their variability across menstrual phases.
The study highlighted significant shifts in vaginal microbiome profiles between the follicular and menstrual phases, particularly in the distribution of community state types (CSTs). During menstruation, CST IV, defined by increased anaerobic bacterial diversity, became more prominent, while CSTs II and V, dominated by Lactobacillus gasseri and Lactobacillus jensenii, respectively, disappeared. Notably, Lactobacillus crispatus was more abundant in endometriosis patients during menstruation, even within the inflammatory environment. This finding suggests a potential immunomodulatory role for L. crispatus, likely tied to its production of lactic acid, which lowers vaginal pH, inhibits pathogenic bacterial growth, and promotes immune homeostasis. By fostering an anti-inflammatory phenotype through the stimulation of cytokines like IL-10 and regulatory immune cells, L. crispatus may help counterbalance the inflammatory state characteristic of endometriosis.
Moreover, the vaginal microbiome during menstruation demonstrated predictive value for endometriosis severity. Specifically, an operational taxonomic unit (OTU) from the genus Anaerococcus strongly correlated with advanced rASRM stages (3–4), marking its potential as a biomarker for disease progression. These findings underscore the diagnostic and therapeutic promise of the vaginal microbiome, particularly L. crispatus and its role in immune modulation. Future research should further investigate these microbial associations, their lactic acid production, and their influence on the immunological environment in endometriosis.
This study provides a foundation for using the vaginal microbiome as a non-invasive diagnostic tool for assessing endometriosis severity. The identification of Anaerococcus as a biomarker for disease stage highlights a significant advancement in linking microbiome alterations to gynecological pathology. Additionally, the potential involvement of Lactobacillus crispatus in modulating local immune responses suggests a dual diagnostic and therapeutic role for microbiome-targeted interventions. However, the findings need validation in larger cohorts due to its pilot nature and small sample size.
In this prospective cohort, women with stage 3/4 endometriosis exhibited a unique microbial profile, characterized by the absence of Atopobium and increased levels of potentially pathogenic genera like Gardnerella, Streptococcus, Escherichia, Shigella, and Ureoplasma in their vaginal and cervical microbiota.
What was studied?
The study focused on exploring the associations between the microbiota of the vaginal, cervical, and gut regions and stage 3–4 endometriosis in women. This research aimed to uncover potential differences in the microbiome composition between women diagnosed with advanced endometriosis and healthy controls, particularly at the genus level of microbial classification.
Who was studied?
The participants included 14 women with histologically proven stage 3–4 endometriosis and 14 healthy controls. These women were carefully selected based on strict criteria to ensure the stability of the microbiota, excluding those who had ever been pregnant or had conditions/medications that could affect the microbiome. All participants belonged to the same ethnicity, and the study managed to maintain a balance between samples collected during different phases of the menstrual cycle in both groups.
What were the most important findings?
The study revealed that while the overall composition of the vaginal, cervical, and gut microbiota was similar between women with and without endometriosis, there were notable genus-level differences. Specifically, Atopobium was absent in the endometriosis group’s vaginal and cervical microbiota. Increases in Gardnerella in the cervical microbiota and Escherichia/Shigella in the gut were more common among those with endometriosis. Sensitivity analyses excluding Lactobacillus showed significant increases in Sneathia, Gardnerella, Streptococcus, Escherichia/Shigella, and Ureaplasma, and a decrease in Alloprevotella in the cervical microbiota of the endometriosis group.
What are the greatest implications of this study?
The findings suggest a potentially significant association between the composition of the female microbiota and the presence of stage 3–4 endometriosis, particularly regarding the absence and presence of specific microbial genera. These differences might offer insights into the pathophysiology of endometriosis and indicate potential diagnostic markers or therapeutic targets. Specifically, the study raises intriguing questions about the direction of causation between altered microbiota and endometriosis. It suggests the microbiome’s potential as both a screening tool for endometriosis and a therapeutic target, depending on whether changes in the microbiome are a cause or a consequence of the disease. The study also underscores the potential utility of gut microbiome analysis as a predictive tool for surgical decisions, such as the need for bowel resection to treat deep infiltrating endometriosis.
Overall, this research lays the groundwork for further studies to clarify the causal relationships between dysbiosis and endometriosis and to explore the microbiome’s role in the disease’s pathogenesis, diagnosis, and treatment.
This case study found that a distinct bacterial composition was observed in deep endometriotic lesions, characterized by a reduced prevalence of Lactobacillus and an increased abundance of Alishewanella, Enterococcus, and Pseudomonas.
What was studied?
The study focused on identifying and comparing the bacterial patterns present in the vaginal fluid, eutopic endometrium, and endometriotic lesions of patients with endometriosis to those found in the vaginal fluid and eutopic endometrium of control patients without the disease. High-throughput DNA sequencing of the 16S rRNA marker gene was utilized to analyze the microbiome profile in these different biological samples from both groups.
Who was studied?
Twenty-one patients participated in this study, divided into two groups: eleven in the control group and ten in the endometriotic group. The control group consisted of women who underwent laparoscopic surgery for benign gynecological diseases or elective tubal ligation, where the absence of endometriosis was confirmed during peritoneal cavity inspection. The endometriotic group included only women with deep endometriosis, confirmed by laparoscopic surgery and histopathology analysis.
What were the most important findings?
The study found that microbiome sequencing of vaginal fluid, eutopic endometrium, and endometriotic lesions typically showed similar profiles, dominated by Lactobacillus, Gardnerella, Streptococcus, and Prevotella. Despite no significant overall differences in microbiome diversity between control and endometriotic patients, deep endometriotic lesions exhibited a distinct bacterial composition with less Lactobacillus and a higher abundance of Alishewanella, Enterococcus, and Pseudomonas.
What are the greatest implications of this study?
The study highlights several implications for endometriosis management: It provides insights into the pathogenesis by showing distinct bacterial compositions in deep lesions, suggesting microbial involvement in lesion development. This leads to the potential for non-invasive diagnostics by identifying specific microbial patterns, opening avenues for biomarker-based detection. Therapeutically, interventions like antibiotics or probiotics could be new treatment strategies if certain bacteria contribute to pathogenesis. The findings emphasize the need for more research to establish causal links between microbiome composition and endometriosis, understand the bacterial influence on the disease, and explore microbiome-based treatments.
This cross-sectional observational study examines how endometriosis affects the bacterial communities of the uterus and cervix, considering the condition's role in inflammation, pain management, and infertility in women.
What was studied?
The study aimed to investigate how endometriosis affects the uterine and cervical bacterial communities. Utilizing next-generation amplicon sequencing of the bacterial 16S rRNA gene, the research sought to identify alterations in these microbiomes associated with endometriosis and to determine if specific bacterial taxa within the cervix could help diagnose active endometriosis, potentially avoiding the need for invasive diagnostic procedures like laparoscopic surgery.
Who was studied?
Nineteen pre-menopausal women undergoing laparoscopic surgery for pelvic pain with suspicion or known endometriosis constituted the experimental group (n=10, with endometriosis stages I-IV), while women undergoing surgery for benign uterine or ovarian conditions served as controls (n=9). The control group was examined during surgery to confirm the absence of endometriotic lesions. The staging of endometriosis for patients in the experimental group was performed using the revised American Society for Reproductive Medicine (rASRM) classification scale.
Key findings of the study include significant differences in bacterial communities between uterine and cervical samples, both in species diversity and abundance, with the uterus displaying a diverse profile of Bacteroidetes and Firmicutes, and the cervix dominated by Lactobacillus. No significant differences in bacterial communities were noted across different endometriosis stages on the day of surgery. However, a distinct cervical bacterial community in a stage III endometriosis patient suggests a link between disease severity and microbiome alterations. Additionally, notable fluctuations in the cervical microbiome were observed over time in this patient, indicating dynamic microbiome changes associated with disease progression and treatment.
What are the greatest implications of this study?
The findings underscore the potential of bacterial community profiling as a diagnostic tool for endometriosis, offering a non-invasive method to identify the disease in asymptomatic, infertile women. This approach could facilitate earlier diagnosis and treatment, potentially improving fertility outcomes and reducing the need for invasive diagnostic surgeries. The study also highlights the dynamic nature of the uterine and cervical microbiomes in relation to endometriosis, suggesting that microbiome alterations could be linked to disease severity and progression. Understanding these microbial community changes opens new avenues for researching endometriosis pathogenesis and developing novel therapeutic strategies that target microbiome modulation. Moreover, the fluctuations observed in the microbiome over time, especially in patients with advanced disease, may offer insights into predicting disease progression and treatment outcomes, including fertility potential post-treatment.
This cross-sectional observational study investigates cervical mucus in women with and without endometriosis, finding similar microbial distributions overall. However, bacteria such as Corynebacterium, Enterobacteriaceae, Flavobacterium, Pseudomonas, and Streptococcus were more common in women with endometriosis, with Enterobacteriaceae and Streptococcus showing significant associations
What was studied?
The study investigated the microbiota in the cervical mucus of women with and without endometriosis using next-generation sequencing (NGS) technologies. It aimed to clarify whether cervical mucus in women with endometriosis is contaminated with bacteria, which could potentially transmigrate into the intrauterine cavity, influencing the pathogenesis of endometriosis. The research explored the bacterial population’s diversity, its correlation with the disease, and how these findings align with previous studies on intrauterine microbial colonization and its role in endometriosis through LPS/TLR4 engagement of the innate immune system.
Who was studied?
The study’s participants consisted of 30 women diagnosed with endometriosis (confirmed by laparoscopy and classified according to the revised American Society for Reproductive Medicine scoring system for stages III-IV) and 39 women without the condition (control group), all of reproductive age (20-44 years). The control group included women with fibroids or benign ovarian tumors other than endometriosis. All subjects had a normal-appearing cervix, were negative for vaginal culturing tests, and had not received endocrine therapy or antibiotics for at least six months before sample collection.
What were the most important findings?
The study highlights several findings about the cervical mucus microbiota in women with and without endometriosis. It found a diverse array of microbiota in both groups, with variations not tied to menstrual cycle phases. The endometriosis group exhibited significantly higher alpha diversity, indicating a more diverse bacterial community. Specific bacteria such as Enterobacteriaceae, Corynebacterium, Pseudomonas, Flavobacterium, and Streptococcus were more prevalent in the endometriosis group, with Enterobacteriaceae and Streptococcus showing significantly higher prevalence.
What are the greatest implications of this study?
The findings suggest that the cervical mucus of women with endometriosis harbors a distinct and more diverse bacterial population than women without the condition. The significant presence of specific bacteria, particularly Enterobacteriaceae and Streptococcus, in women with endometriosis may play a role in the disease’s pathogenesis through mechanisms involving bacterial contamination, immune system engagement, and inflammatory responses. These insights open new avenues for understanding endometriosis’s pathophysiology, potentially leading to novel diagnostic and therapeutic strategies. Further, the study implies a possible link between cervical mucus microbiota and adverse pregnancy outcomes, highlighting the need for additional research to explore the mechanistic connections between microbial colonization and endometriosis and its implications for fertility and pregnancy.
This cross-sectional observational study examined the link between inflammatory markers (IL-6, IL-10, IL-13, TNF-α), peritoneal fluid bacterial flora, and infertility in endometriosis patients. Results showed significantly higher white cell counts and elevated levels of inflammatory markers in endometriosis patients compared to controls. Logistic regression confirmed significant associations between these inflammatory markers and infertility.
What was studied?
The study investigated the relationship between inflammatory markers (IL-6, IL-10, IL-13, and TNF-α), the composition of bacterial flora in peritoneal fluid, and infertility in patients with endometriosis.
Who was studied?
The participants included 55 patients diagnosed with endometriosis and infertility (observation group) attending a Gynecology Clinic from June 2014 to July 2017 and 30 individuals without endometriosis or infertility issues (control group).
What were the most important findings?
The study found elevated white cell counts (monocytes, neutrophils, eosinophils, and basophils) and higher levels of inflammatory cytokines (IL-6, IL-10, IL-13, and TNF-α) in the peritoneal fluid of endometriosis patients with infertility compared to controls. A significant correlation between these inflammatory markers and endometriosis associated with infertility was also established.
What are the greatest implications of this study?
The study implies that inflammatory factors in peritoneal fluid play a crucial role in the pathophysiology of infertility associated with endometriosis. These findings suggest that inflammatory cytokines (IL-6, IL-10, IL-13, and TNF-α) could serve as significant biomarkers for diagnosing and understanding the mechanisms of endometriosis-related infertility.
This study used high-throughput DNA sequencing to show that murine endometriosis alters gut microbiota, notably increasing the Firmicutes/Bacteroidetes ratio and Bifidobacterium levels by day 42, indicating disease-specific dysbiosis. It underscores the need for further research on the long-term effects of endometriosis on gut microbiota and its bidirectional interaction with the host.
What was studied?
The research focused on investigating the impact of murine endometriosis on gut microbiota composition using high-throughput DNA sequencing to explore how the disease affects intestinal microbial communities.
Who was studied?
The study subjects were mice. These animals were divided into two groups: one group with induced endometriosis through the intraperitoneal injection of endometrial tissues and a mock group that served as a control.
What were the most important findings?
The study’s key findings include the emergence of a distinct gut microbiota composition in mice with endometriosis by day 42 post-modeling, highlighted by an increased Firmicutes/Bacteroidetes ratio and elevated levels of Bifidobacterium. These changes suggest a specific dysbiosis associated with endometriosis.
What are the greatest implications of this study?
The study’s most significant implications lie in its pioneering use of high-throughput DNA sequencing to link endometriosis with specific changes in gut microbiota, highlighting the disease’s potential to induce dysbiosis. It suggests the importance of further research to understand the long-term effects of endometriosis on gut microbiota and the bidirectional interactions between the host and its microbiota. This could lead to novel insights into the pathophysiology of endometriosis and inform new therapeutic strategies targeting the gut microbiome.
Did you know?
Gut microbiota predict endometriosis better than vaginal microbiota.
Did you know?
The radical mastectomy for breast cancer was standard practice for nearly 60 years before less invasive options were proven effective.
A case-controlled molecular study on 32 women, half with endometriosis and half without, investigated microbial colonization in the intrauterine environment and ovarian cystic fluid. It found significant bacterial variations, with certain bacteria types increasing or decreasing, particularly after treatment with gonadotropin-releasing hormone agonist (GnRHa). The study suggests GnRHa treatment might promote sub-clinical infections in the intrauterine and ovarian environments.
The research focused on investigating microbial colonization in women’s intrauterine environment and cystic fluid, utilizing a molecular approach to detect bacterial presence. This involved examining variations in bacterial types and their implications in the context of endometriosis and treatment effects.
The study included 32 women, evenly divided between those diagnosed with endometriosis and those without the condition. Each group was further split, with half receiving gonadotropin-releasing hormone agonist (GnRHa) treatment, to explore the treatment’s impact on microbial colonization.
Key findings revealed a broad range of bacterial presence in both endometrial swabs and cystic fluids, with significant changes in bacterial families (decrease in Lactobacillacae and increase in Streptococcaceae, Staphylococaceae, and Enterobacteriaceae) observed in GnRHa-treated women with endometriosis. The 16S metagenome assay was more effective than traditional culture methods, particularly in identifying bacteria in ovarian endometrioma cystic fluid.
The study’s findings suggest the presence of sub-clinical infections in the intrauterine environment and ovarian endometrioma cystic fluid, particularly following GnRHa treatment. This raises concerns about the potential for GnRHa therapy to promote silent infections, indicating a need for careful consideration and monitoring of such treatments in women with endometriosis.
This study investigated the long-term effects of gonadotropin-releasing hormone agonists (GnRHa), with and without hormone replacement therapy (HRT), on bone mineral density (BMD) in women with endometriosis, following up to six years after treatment.
Who was studied?
The study included forty-nine symptomatic women diagnosed with endometriosis via laparoscopy, who volunteered to participate in the randomized trial. These women were undergoing treatment with long-acting GnRH agonists and were subsequently monitored for up to six years.
What were the most important findings?
The study’s key findings indicate that long-term use of GnRH agonists results in a reduction in bone mineral density (BMD) at the lumbar spine and hip, a reduction that was not fully recovered even up to six years post-treatment. Additionally, the inclusion of hormone replacement therapy (HRT) did not significantly influence bone mineral density when compared to those who did not receive HRT. The results also demonstrated a considerable range of individual variability in BMD response among the participants, suggesting that the effects of GnRH agonists on BMD can vary significantly among different women.
What are the greatest implications of this study?
The implications of these findings are substantial for the management of endometriosis. The study underscores the potential risks associated with long-term GnRH agonist therapy, particularly concerning bone health, which may significantly influence treatment decisions and patient counseling. It also highlights the critical need for monitoring bone mineral density (BMD) in women undergoing prolonged GnRH agonist therapy, suggesting that this monitoring should possibly extend beyond the cessation of treatment. Furthermore, the observed variability in BMD response among participants indicates a need for individualized treatment plans, which may include exploring alternative therapies or preventive measures against bone density loss. Additionally, these findings could drive further research aimed at optimizing ‘add-back’ therapy to balance the effectiveness of GnRH agonists in managing endometriosis symptoms with the mitigation of side effects such as bone loss.
This case control study explored the gut microbiota in stage 3/4 endometriosis (EM) by comparing fecal and blood samples from 12 EM patients and 12 controls using 16S rRNA sequencing. Results showed reduced α diversity and an increased Firmicutes/Bacteroidetes ratio in EM patients, with notable taxonomic differences and elevated estradiol and IL-8 levels. The study suggests microbiota-related pathways may influence EM, indicating directions for further research.
What was studied?
The study investigated the role of gut microbiota in endometriosis (EM), focusing on its differences between individuals with stage 3/4 EM and healthy controls and how these differences correlate with serum hormone levels and inflammatory cytokines.
Who was studied?
The research involved 12 patients diagnosed with stage 3/4 endometriosis and 12 healthy control subjects. The researchers compared their gut microbiota compositions and measured serum levels of hormones and inflammatory cytokines.
What were the most important findings?
Key findings included a lower α diversity of gut microbiota and a higher Firmicutes/Bacteroidetes ratio in the EM group compared to controls. Significant differences in the abundances of various taxa were observed, along with higher serum levels of estradiol (E2) and interleukin-8 (IL-8) in the EM group. The study also identified correlations between specific microbial abundances and levels of estradiol and IL-8.
What are the greatest implications of this study?
The study’s implications suggest that the gut microbiota may play a significant role in the pathophysiology of endometriosis through its influence on hormonal and inflammatory pathways. These findings open potential avenues for novel therapeutic strategies targeting the gut microbiota in endometriosis management and highlight the need for further research to verify and expand upon these preliminary observations.
Antibiotic treatment in mice with surgically-induced endometriosis reduced disease progression by targeting gut bacteria, significantly decreasing lesion size and inflammation. This study suggests a potential gut microbiota link to endometriosis and indicates a novel treatment approach, warranting further investigation for human application.
What was studied?
The research investigated the impact of antibiotic treatment on the progression of endometriosis, specifically examining how altering the gut microbiota with antibiotics affects the development of endometriotic lesions in a mouse model.
Who was studied?
Mice subjected to surgically induced endometriosis were studied. These mice were treated with either broad-spectrum antibiotics or metronidazole to assess the effects of these treatments on the progression of endometriosis.
What were the most important findings?
The study found that antibiotic therapy, especially broad-spectrum antibiotics, significantly reduced the size and proliferation of endometriotic lesions compared to vehicle-treated mice. It also reduced inflammatory responses within the lesions. Treatment with metronidazole alone, unlike neomycin, resulted in significantly smaller lesions. Furthermore, fecal microbiota transfer from mice with endometriosis could restore lesion growth and inflammation in metronidazole-treated mice.
What are the greatest implications of this study?
These results suggest a crucial role of gut bacteria in promoting endometriosis progression in mice, indicating that manipulating the gut microbiota could offer a new therapeutic strategy for managing endometriosis. If these findings apply to humans, they could lead to the development of improved diagnostic tools and personalized treatment strategies, potentially with fewer side effects than current hormone therapy and surgical options. Further research is needed to understand the mechanisms involved and to explore the translatability of these findings to human patients.
This pilot study analyzed gut and vaginal microbiomes in 59 women (35 with endometriosis, 24 controls) using 16S rRNA sequencing and machine learning to explore their diagnostic potential for endometriosis. Findings indicate microbiome variations with the menstrual cycle and disease severity, suggesting that vaginal microbiome profiles could predict endometriosis stages, offering a novel, less-invasive diagnostic method.
What was studied?
The study focused on characterizing the gut and vaginal microbiome profiles of women with endometriosis compared to controls without the disease, exploring the potential of these profiles as less-invasive diagnostic tools for assessing the severity of endometriosis.
Who was studied?
Fifty-nine women participated in the study, including 35 with endometriosis and 24 control subjects. Rectal and vaginal samples were collected from all participants at two different periods of their menstrual cycle.
What were the most important findings?
Significant findings included variations in the distribution of vaginal community state types (CSTs) across different phases of the menstrual cycle and differences in gut and vaginal microbiome profiles between patients with varying stages of endometriosis as classified by the revised American Society for Reproductive Medicine (rASRM) stages. Machine-learning models could predict the severity of endometriosis (stages 1-2 vs. 3-4) based on these microbiome profiles, with Anaerococcus genus showing the highest predictive value.
What are the greatest implications of this study?
The study suggests that analysis of the vaginal microbiome could serve as a novel, less-invasive method to diagnose and predict the stage of endometriosis. This approach could potentially lead to earlier and more accurate diagnoses of endometriosis, improving treatment planning and outcomes for affected women.
Did you know?
Gut microbiota predict endometriosis better than vaginal microbiota.
This study identifies microbiota alterations in ovarian endometrioma, showing distinct microbial shifts in peritoneal fluid extracellular vesicles. Enrichment of Pseudomonas and Acinetobacter, alongside depletion of Propionibacterium and Actinomyces, suggests inflammatory contributions to pathogenesis. Findings highlight the diagnostic potential of microbiota-derived EVs in endometrioma management.
This study examined the microbiota composition in the peritoneal fluid of women with ovarian endometrioma, focusing specifically on microbiome analyses of extracellular vesicles (EVs). Extracellular vesicles are nanometer-sized particles released by cells, including bacteria, that carry microbial DNA and signaling molecules. The research aimed to determine if women with ovarian endometrioma exhibit distinct microbiota profiles in their peritoneal fluid compared to women without endometriosis. Microbial DNA was sequenced using next-generation sequencing (NGS) of the 16S rDNA V3–V4 regions, allowing for detailed taxonomic identification and comparative analysis.
The study included 45 women diagnosed with histological evidence of ovarian endometrioma and 45 surgical controls confirmed to be free of endometriosis. Participants were recruited from Asan Medical Center, and peritoneal fluid samples were collected during laparoscopic procedures. Women with endometriosis were classified as having advanced-stage disease, and none of the participants had taken antibiotics, probiotics, or hormonal treatments for 12 weeks prior to sample collection.
The microbiota composition of extracellular vesicles in peritoneal fluid was markedly different between women with ovarian endometrioma and controls. Alpha diversity analysis showed no significant differences in species richness between groups, but beta diversity analysis revealed distinct microbial community shifts in the endometriosis group (p < 0.001). Taxonomic profiling demonstrated increased abundances of Acinetobacter, Pseudomonas, Streptococcus, and Enhydrobacter in women with ovarian endometrioma. Conversely, Propionibacterium, Actinomyces, and Rothia were significantly decreased in the endometriosis group (p < 0.05).
At the family level, Pseudomonadaceae and Moraxellaceae were notably enriched in the endometriosis samples, while Veillonellaceae, Propionibacteriaceae, and Actinomycetaceae were reduced. The data also indicated a significant increase in Pseudomonadales and a decline in Actinomycetales at the order level (p < 0.05). These findings suggest that the altered microbiota composition in extracellular vesicles of the peritoneal fluid may contribute to the inflammatory microenvironment observed in ovarian endometrioma.
| Microbial Group | Ovarian Endometrioma | Clinical Implications |
|---|---|---|
| Acinetobacter | Increased | Linked to inflammation and immune response in the peritoneal cavity |
| Pseudomonas | Increased | Associated with pathogenic processes in ovarian endometrioma |
| Streptococcus | Increased | Potential contributor to local inflammation and immune modulation |
| Enhydrobacter | Increased | May play a role in extracellular signaling and immune responses |
| Propionibacterium | Decreased | Loss may disrupt protective anti-inflammatory effects |
| Actinomyces | Decreased | Reduced presence suggests compromised mucosal defenses |
| Rothia | Decreased | May contribute to a disrupted microbial ecosystem |
| Pseudomonadaceae (Family) | Enriched | Suggests pathogenic influence in peritoneal fluid |
| Moraxellaceae (Family) | Enriched | Associated with peritoneal inflammation |
| Veillonellaceae, Propionibacteriaceae, Actinomycetaceae (Families) | Reduced | Indicates loss of protective and commensal populations |
The study provides compelling evidence that women with ovarian endometrioma possess distinct microbial communities in the peritoneal environment, carried via extracellular vesicles. The enrichment of pathogenic genera such as Pseudomonas and Acinetobacter, alongside the depletion of protective taxa like Propionibacterium and Actinomyces, suggests that these microbial imbalances could play a role in local inflammation and disease progression. These findings underscore the potential of microbiota-derived EVs as non-invasive biomarkers for ovarian endometrioma and open the door for targeted microbiome-modulating therapies to alleviate inflammatory responses and halt disease progression.
This cross-sectional observational study compared microbiota in various reproductive tract locations finding significant microbiota changes in endometriosis patients, especially a decrease in Lactobacillus and increase in specific bacteria in the cervical area.
What was studied?
The study investigated the microbiota distribution across the entire female reproductive tract of endometriosis (EMS) patients and non-EMS women, aiming to identify EMS-specific bacterial species and examine the relationship between flora and disease development.
Who was studied?
Fifty women undergoing laparoscopic surgery for benign gynecological diseases or pelvic endometriosis at Peking University Shenzhen Hospital were studied. They were divided into two groups: 36 with pelvic endometriosis (stages I-IV) and 14 controls without endometriosis symptoms.
What were the most important findings?
Significant differences in the microbiota distribution were observed, especially a decrease in Lactobacillus in the upper reproductive tract of EMS patients. Specific Operational Taxonomic Units (OTUs), particularly Sphingobium sp. and Pseudomonas viridiflava, were identified as significantly enriched in the endometrium and peritoneal fluid of EMS patients, suggesting their potential role in EMS pathogenesis.
What are the greatest implications of this study?
The study offers a new perspective on the pathogenesis of endometriosis, emphasizing the role of specific bacteria in its development. Identifying microbiota changes associated with EMS could lead to novel diagnostic markers and therapeutic targets, enhancing our understanding of the disease and potentially leading to more effective management strategies for endometriosis and other female reproductive tract diseases.
This study explores the relationship between fecal metabolomics and gut microbiota in endometriosis (EMS) mice, finding key metabolic changes and decreased microbiota diversity. Significant pathways, like bile acid biosynthesis and ALA metabolism, were identified, suggesting fecal metabolites affected by dysbacteriosis as potential EMS markers.
What was studied?
The study investigated the interaction between fecal metabolomics and gut microbiota in mice with endometriosis (EMS), aiming to identify metabolic changes and microbiota diversity associated with the disease.
Who was studied?
Female C57BL/6J mice, utilized to construct an EMS model, were the subjects of this research, allowing for the examination of fecal metabolites and gut microbiota composition.
What were the most important findings?
Significant findings included the identification of 156 differential metabolites, decreasing the diversity and abundance of gut microbiota in EMS mice, and involving key metabolic pathways such as bile acid biosynthesis and alpha-linolenic acid (ALA) metabolism. Notably, increased levels of chenodeoxycholic and ursodeoxycholic acids and decreased levels of ALA and 12,13-EOTrE were found in EMS mice feces.
What are the greatest implications of this study?
The study suggests that the identified abnormal fecal metabolites, influenced by gut dysbiosis, may be potential markers for diagnosing EMS. This finding opens new avenues for understanding EMS pathogenesis and developing non-invasive diagnostic tools based on fecal metabolite profiles.
Did you know?
Gut microbiota predict endometriosis better than vaginal microbiota.
Did you know?
Estimates suggest that 1 in 7 women in the United States is affected by Chronic Pelvic Pain (CPP).
This study examines the role of the vaginal microbiome in distinguishing chronic pelvic pain caused by endometriosis and adenomyosis. Findings highlight specific microbial signatures associated with pain severity, offering potential non-invasive biomarkers for differential diagnosis and targeted therapeutic strategies.
This study investigated whether the composition of the vaginal microbiome could serve as a diagnostic biomarker to differentiate chronic pelvic pain (CPP) caused by endometriosis or adenomyosis (EM/AM) from other causes of chronic pelvic pain syndrome (CPPS) in women. Using 16S rRNA sequencing (V4 region), the researchers profiled the vaginal microbiota of 37 women with EM/AM-associated CPP, 25 with CPPS from other causes, and 66 healthy controls without CPPS. Additionally, the study explored whether combining vaginal microbial markers with serum CA125 could improve differential diagnostic accuracy.
The study included 128 premenopausal women attending the gynecology department of Peking Union Medical College Hospital. These were stratified into three groups: 37 women with surgically confirmed EM/AM-associated CPP, 25 women with non-EM/AM CPPS (adhesions, hydrosalpinx, infertility), and 66 women without any chronic pelvic pain. All participants were HPV-negative, had not recently used antibiotics or vaginal products, and were matched for age, gravidity, parity, and contraceptive method to control for confounding variables.
The vaginal microbiome of women with EM/AM-associated CPP exhibited significantly higher alpha diversity than those in the CPPS and healthy control groups. Taxonomic analyses revealed distinct microbial signatures: increased abundance of Clostridium butyricum, Clostridium disporicum, Alloscardovia omnicolens, and Veillonella montpellierensis, alongside a marked depletion of Lactobacillus jensenii, Lactobacillus reuteri, and Lactobacillus iners. These differentially abundant taxa serve as potential microbiome biomarkers.
Diagnostic performance analysis demonstrated that a combination of microbial biomarkers (specifically, a relative abundance of Clostridium disporicum >0.001105% and Lactobacillus reuteri <0.1911349%) yielded 81.08% sensitivity and 52% specificity for identifying EM/AM-associated CPP. When combined with serum CA125 levels, sensitivity increased to 89.19%, although specificity remained unchanged. Functional predictions via PICRUSt revealed enrichment of metabolic pathways such as amino acid metabolism, energy metabolism, and metabolism of cofactors and vitamins in EM/AM patients, along with downregulation of membrane transport and nucleotide metabolism compared to controls. These shifts may reflect microbial contributions to inflammation and pain signaling pathways implicated in EM/AM-associated CPP.
From a microbiome signature standpoint, the enriched taxa—particularly Clostridium disporicum and Alloscardovia omnicolens—emerge as Major Microbial Associations (MMAs) due to their consistent elevation in EM/AM patients. Conversely, Lactobacillus jensenii and L. reuteri, known for their protective, anti-inflammatory properties, are depleted, suggesting their role in maintaining vaginal eubiosis and preventing EM/AM-associated pathogenesis.
This research provides compelling evidence that the vaginal microbiome harbors discriminative microbial signatures capable of differentiating EM/AM-associated CPP from other forms of chronic pelvic pain. The incorporation of specific microbial biomarkers, particularly when paired with serum CA125, may improve non-invasive diagnostic accuracy, enabling earlier and more targeted therapeutic intervention. Clinically, these findings underscore the potential of microbiome-informed diagnostics for gynecological conditions where conventional markers fall short. More broadly, this study suggests that vaginal dysbiosis, characterized by Lactobacillus depletion and enrichment of saccharolytic and anaerobic species, could be causally linked to EM/AM pathogenesis, possibly via inflammatory or metabolic pathways. Future studies incorporating metagenomic or metabolomic analyses are warranted to functionally validate these microbial associations and to explore the feasibility of microbial modulation as a therapeutic strategy.
This case-control study investigates the relationship between genital tract microbiota and endometriosis using 16s-rRNA sequencing. Findings show Atopobium prevalence in endometriosis with adenomyosis cases, highlighting microbiota's distinct functions.
What was studied?
The study investigated the relationship between the genital tract microbiota and endometriosis, particularly focusing on how microbiota diversity and specific bacteria like Atopobium might be associated with the disease.
Who was studied?
68 participants, from whom 134 samples were collected from the cervical canal, posterior fornix, and uterine cavity for 16s-rRNA sequencing, were included in the study.
What were the most important findings?
Key findings included no significant differences in alpha diversity between the cervical canal and posterior fornix. However, the microbiota profile of patients with adenomyosis and endometriosis differed markedly from the control group, with Atopobium showing significant prevalence in these patients. While no specific biomarkers were identified, PICRUSt analysis revealed several characteristic microbiota functions.
What are the greatest implications of this study?
The study suggests a potentially significant role of microbiota, particularly Atopobium, in the pathogenesis of endometriosis combined with adenomyosis. This finding could lead to new insights into the microbiota-immune-endometriosis system interaction, offering new avenues for understanding and possibly treating endometriosis and adenomyosis. Further research is needed to verify the functions of the microbiota identified and their direct association with the diseases.
This case control study explores the gut microbiota's association with endometriosis in women, comparing 66 patients to 198 controls. Using 16S rRNA sequencing, it was found that patients have lower diversity in their gut bacteria and significant differences in the abundance of 12 bacterial types, suggesting that endometriosis may influence gut microbiota composition.
What was studied?
The study examined the gut microbiota in women with endometriosis compared to healthy controls. It aimed to explore differences based on disease localization, symptoms, or treatment and assess the gut microbiota’s potential role in the pathogenesis of endometriosis.
Who was studied?
66 women diagnosed with endometriosis at Skåne University Hospital were studied alongside 198 matched controls from the Malmö Offspring Study, assessing their gut microbiota through 16S rRNA sequencing.
What were the most important findings?
Significant findings include higher overall microbial diversity in controls compared to endometriosis patients, with specific differences in the abundance of 12 bacteria types between the two groups. After adjusting for false discovery rates, no significant microbiota differences were found within the endometriosis cohort.
What are the greatest implications of this study?
The study implies that gut microbiota may be altered in individuals with endometriosis, suggesting a possible link between gut microbiota and the pathogenesis or symptomatology of endometriosis. These findings highlight the need for further research on the gut microbiota’s role in endometriosis, potentially leading to new diagnostic and treatment strategies.
This study investigated the impact of induced endometriotic lesions on gut microbiota in mice, using GFP+ uterine tissue transplantation. Despite successful lesion formation, no significant changes in gut microbiota composition were observed in the acute phase, suggesting endometriosis may not cause pronounced dysbiosis during early lesion development.
What was studied?
The study investigated whether the induction of endometriosis in mice affects the composition of their gut microbiota. It tested this by transplanting uterine tissue fragments into mice and analyzing changes in the gut microbiota before and after endometriosis induction.
Who was studied?
Female C57BL/6 wild-type mice and GFP+ transgenic donor mice were used. Uterine tissue from the donor mice was transplanted into the peritoneal cavity of the wild-type mice to induce endometriosis, with sham-transplanted mice serving as controls.
What were the most important findings?
Endometriotic lesions successfully developed in the mice, but the study found no significant alterations in the gut microbiota composition within the 21-day observation period. The bacterial community remained stable, indicating no early-phase intestinal dysbiosis due to endometriosis induction.
What are the greatest implications of this study?
The study hypothesizes that there is a bi-directional relationship between gut dysbiosis and endometriosis, where alterations in the gut microbiota may influence the development and progression of endometriosis and vice versa. Although this particular study did not find significant changes in the gut microbiota composition within the early phase of endometriosis induction in mice, it suggests the possibility that the gut microbiota could be involved in hormone-related, inflammatory, angiogenic, and vasculogenic processes associated with endometriosis.
Other studies’ findings, which reported dysbiosis following endometriosis induction, further support the idea of a complex interaction between endometriosis and the gut microbiota. This interaction could potentially impact estrogen metabolism, systemic inflammation, and stem cell homeostasis, all of which are implicated in the pathogenesis of endometriosis. However, the study calls for more research to clarify this relationship, including studies on microbial activity and metabolic function, to understand how gut microbiota might affect endometriosis fully.
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Research on relaxed fibronectin as a target for imaging endometriotic lesions showed that a novel radiotracer binds preferentially to this protein in disease areas. This finding could lead to improved diagnostic techniques for endometriosis, offering a non-invasive method to detect lesions accurately, thereby enhancing treatment planning and patient outcomes.
The study investigated relaxed fibronectin as a novel target for imaging endometriotic lesions. Researchers explored using a preclinical radiotracer, [111In]In-FnBPA5, which binds specifically to relaxed fibronectin, an extracellular matrix protein involved in the pathogenesis of diseases like cancer and fibrosis.
The study involved preclinical experiments using mice and immunohistochemical analysis on tissue samples from mice and patients diagnosed with endometriosis.
The radiotracer [111In]In-FnBPA5 accumulated in the mouse uterus, with uptake varying according to the estrous cycle, suggesting an increased abundance of relaxed fibronectin during estrogen-dependent phases. Immunohistochemical analysis on patient-derived tissues showed that relaxed fibronectin is preferentially located near the endometriotic stroma, supporting its potential as a target for imaging endometriosis.
The findings that [111In]In-FnBPA5 uptake varies in the mouse uterus with the estrous cycle, indicating increased relaxed fibronectin during estrogen-dependent phases, hold significant implications for future research on endometriosis.
Biomarker Identification: Understanding the fluctuation of relaxed fibronectin could help identify biomarkers for endometriosis, enabling earlier and more accurate diagnosis.
Pathogenesis Insights: These results suggest that estrogen-driven changes in fibronectin might play a role in the development or exacerbation of endometriosis. This could lead to a better understanding of the disease’s underlying mechanisms.
Targeted Therapies: By highlighting the relationship between estrogen, fibronectin, and endometrial tissue changes, new therapeutic targets may be identified, paving the way for treatments that modulate fibronectin or its pathways.
Diagnostic Imaging: The study suggests that targeting relaxed fibronectin could significantly improve the diagnostic imaging of endometriosis. This approach may lead to developing a specific radiotracer for noninvasive detection of endometriotic lesions, potentially enhancing diagnosis accuracy and aiding in better disease management.
Clinical Application: The researchers also suggest using gallium-68 for potential clinical application, which could further refine imaging techniques and improve patient outcomes.
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This study examined the presence of metalloestrogens in ectopic endometrial tissue from fifty women diagnosed with endometriosis. Cadmium, nickel, and lead were found in all tissue samples, with nickel and lead showing particularly high concentrations. These findings suggest that metalloestrogens play a role in the etiology of endometriosis by interacting with estrogen receptors, emphasizing environmental pollutants' role in endometriosis progression.
This study investigated the presence of metalloestrogens in ectopic endometrial tissue from women with endometriosis. Metalloestrogens, heavy metals that can mimic estrogen and may contribute to estrogen-dependent diseases, were the focus, particularly regarding their potential role in the persistence and pathology of endometriosis. The researchers specifically analyzed levels of cadmium, nickel, and lead in ectopic endometrial samples using advanced metal detection techniques, Total Reflection X-ray Fluorescence (TXRF) and Graphite Furnace Atomic Absorption Spectroscopy (GFASS).
The study included fifty women of reproductive age diagnosed with endometriosis via laparoscopy or laparotomy at the Professorial Gynecology Unit of the National Hospital, Colombo, Sri Lanka, during 2009-2010. The participants underwent these procedures for diagnosis or treatment, and endometriotic tissue samples were collected during surgery. The participants presented with varied symptoms like infertility, dysmenorrhea, chronic pelvic pain, and endometriomas.
The study found significant levels of cadmium, nickel, and lead in all ectopic endometrial tissue samples. Specifically, geometric mean concentrations were reported as follows: cadmium (2.861 μg/Kg), nickel (17.547 μg/Kg), and lead (25.785 μg/Kg). The concentrations varied by tissue site, with the ovarian endometrioma wall showing higher, though not statistically significant, metal levels than pelvic endometrial patches or nodules in the pouch of Douglas.
This study is one of the first to identify and quantify metalloestrogens in ectopic endometrial tissue, shedding light on a possible environmental and molecular link to endometriosis. It underscores the mechanism by which these metals could perpetuate endometriosis, given their ability to interact with estrogen receptors in ectopic tissue. The implications are substantial for public health, especially given the widespread environmental exposure to metals such as cadmium, nickel, and lead. These findings suggest that environmental pollution may play a significant role in the etiology and progression of endometriosis, calling for further investigation into the estrogen-mimicking properties of environmental metals and their regulation. Additionally, the study highlights the need for preventive measures to reduce heavy metal exposure to nickel and lead, particularly among women susceptible to estrogen-related diseases.
2025-01-15 18:57:51
Zinc added as a potential STOP majorHigher dietary zinc intake is significantly associated with an increased endometriosis risk. These findings highlight the need for cautious zinc use, especially in at-risk populations, to avoid adverse effects.
2024-12-29 07:49:04
Cruciferous Vegetables added to STOPs majorStudy finds that the consumption of cruciferous vegetables like broccoli, cauliflower, cabbage, and brussel sprouts are associated with an increased risk of endometriosis.
Chronic Pelvic Pain (CPP) is persistent pain in the pelvic region lasting six months or longer, often multifactorial, impacting physical and emotional well-being, and associated with various medical conditions.
Infertility is the inability to conceive after 12 months of regular, unprotected sex. It affects both men and women and can be due to various physical, hormonal, or genetic factors. Treatments include medication, surgery, assisted reproductive technologies, and lifestyle changes.
Retrograde menstruation theory holds that during menstruation, some endometrial tissue reverses through the fallopian tubes into the pelvic cavity. It implants on pelvic organs, thickens, breaks down, and bleeds cyclically, causing inflammation, pain, and scar tissue, characteristic of endometriosis.
Chronic Pelvic Pain (CPP) is persistent pain in the pelvic region lasting six months or longer, often multifactorial, impacting physical and emotional well-being, and associated with various medical conditions.
Infertility is the inability to conceive after 12 months of regular, unprotected sex. It affects both men and women and can be due to various physical, hormonal, or genetic factors. Treatments include medication, surgery, assisted reproductive technologies, and lifestyle changes.
An endometrioma is a type of ovarian cyst filled with old blood, arising from endometrial tissue outside the uterus, typically causing pain and potentially impacting fertility.
Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by symptoms such as abdominal pain, bloating, and altered bowel habits. Recent research has focused on the gut microbiota's role in IBS, aiming to identify specific microbial signatures associated with the condition.
Retrograde menstruation theory holds that during menstruation, some endometrial tissue reverses through the fallopian tubes into the pelvic cavity. It implants on pelvic organs, thickens, breaks down, and bleeds cyclically, causing inflammation, pain, and scar tissue, characteristic of endometriosis.
Müllerianosis theory posits that embryonic Müllerian duct remnants misplace and differentiate, forming endometrial-like tissues in non-uterine locations post-puberty, contributing to conditions like endometriosis.
Lymphovascular Metastasis Theory posits that endometrial cells spread via blood and lymph systems, causing distant endometriosis. Evidence is promising but limited.
The Microbial Metallomics Theory of Endometriosis proposes that heavy metals, microbial metallophores, and immune dysregulation drive endometriosis progression. This novel framework links environmental toxins, microbiome shifts, and metalloestrogen activity, offering new insights into disease mechanisms and potential treatments, including metal chelation, microbiome modulation, and immune recalibration.
Retrograde menstruation theory holds that during menstruation, some endometrial tissue reverses through the fallopian tubes into the pelvic cavity. It implants on pelvic organs, thickens, breaks down, and bleeds cyclically, causing inflammation, pain, and scar tissue, characteristic of endometriosis.
The environmental theory of endometriosis suggests exposure to toxins like dioxins and PCBs may contribute to its development by disrupting hormones, modulating the immune system, and promoting inflammation.
Coelomic Metaplasia Theory could help explain the cases of endometriosis in men or in women who are not yet menstruating.
Müllerianosis theory posits that embryonic Müllerian duct remnants misplace and differentiate, forming endometrial-like tissues in non-uterine locations post-puberty, contributing to conditions like endometriosis.
The Genetic and Epigenetic Theory of Disease posits that genetic mutations and epigenetic modifications, influenced by environment and lifestyle, impact gene function and disease development, providing insights into disease mechanisms and potential personalized treatments.
Lymphovascular Metastasis Theory posits that endometrial cells spread via blood and lymph systems, causing distant endometriosis. Evidence is promising but limited.
The Microbiome Theory posits that gut balance promotes health, while imbalances (dysbiosis) cause disease, suggesting restoration as treatment.
Microbial Metallomics is the study of how microorganisms interact with metal ions in biological systems, particularly within the human microbiome.
Microbiome signatures define the unique compositions and functions of microbial communities in environments like the human gut, skin, or oral cavity. Characterized by the types and abundances of microbes such as bacteria, viruses, fungi, and archaea, as well as their genetic profiles and metabolites, these signatures are pivotal for diagnosing, understanding, and managing health and disease.
Metabolomic signatures are unique metabolite patterns linked to specific biological conditions, identified through metabolomics. They reveal underlying biochemical activities, aiding in disease diagnosis, biomarker development, and personalized medicine. The microbiome significantly affects these signatures, influencing health and disease outcomes through metabolic interactions.
Transition metals like iron, zinc, copper, and manganese are crucial for the enzymatic machinery of organisms, but their imbalance can foster pathogenic environments within the gastrointestinal tract.
Estrogen is a steroid hormone primarily found in women, crucial for reproductive health, secondary sexual characteristics, and various physiological processes. It regulates menstrual cycles, supports pregnancy, and influences bone density and cardiovascular health. Dysregulation of estrogen levels can lead to various disorders and health complications.
The chronic inflammatory state of endometriosis affects energy metabolism, particularly altering glutamine and glutamate levels in tissues. These shifts in amino acid, lipid, sugar, and organic acid metabolisms create a distinct profile for endometriosis.
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
Matrix Metalloproteinases (MMPs) are zinc-dependent enzymes that regulate extracellular matrix remodeling, with critical roles in health, disease, and interactions with the microbiome.
Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol.
Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol.
Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by symptoms such as abdominal pain, bloating, and altered bowel habits. Recent research has focused on the gut microbiota's role in IBS, aiming to identify specific microbial signatures associated with the condition.
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol.
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.
Matrix Metalloproteinases (MMPs) are zinc-dependent enzymes that regulate extracellular matrix remodeling, with critical roles in health, disease, and interactions with the microbiome.
Nutritional immunity restricts metal access to pathogens, leveraging sequestration, transport, and toxicity to control infections and immunity.
Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein classified as a postbiotic with immunomodulatory, antimicrobial, and prebiotic-like properties.
The estrobolome is a group of gut bacteria that metabolize estrogen, impacting its levels and effects in the body. By modulating estrogen reabsorption and excretion, the estrobolome influences hormonal balance and risks of estrogen-related conditions, making it a target for therapeutic interventions.
Estrogen is a steroid hormone primarily found in women, crucial for reproductive health, secondary sexual characteristics, and various physiological processes. It regulates menstrual cycles, supports pregnancy, and influences bone density and cardiovascular health. Dysregulation of estrogen levels can lead to various disorders and health complications.
Major Microbial Associations (MMAs) are fundamental in understanding disease-microbiome interactions and play a crucial role in advancing microbiome-targeted interventions aimed at treating or preventing diseases through microbial modulation.
Escherichia coli (E. coli) is a versatile bacterium, from gut commensal to pathogen, linked to chronic conditions like endometriosis.
Streptococcus is a genus of gram-positive, facultatively anaerobic bacteria commonly found in pairs or chains. Important human pathogens include Streptococcus pneumoniae, Streptococcus pyogenes (group A strep), and Streptococcus agalactiae (group B strep).
β-glucuronidase in the gut microbiome breaks down metabolites, drugs, and hormone conjugates like estrogen, aiding microbial energy use and nutrient cycling. Its activity influences drug efficacy and hormone levels, maintaining estrogen balance and impacting health. Disruption in this process can lead to estrogen-related diseases, such as gynecological cancers and menopausal syndrome, and increase colorectal cancer risks by reactivating carcinogens, highlighting its pivotal role in linking microbial actions to host physiological processes.
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
Major Microbial Associations (MMAs) are fundamental in understanding disease-microbiome interactions and play a crucial role in advancing microbiome-targeted interventions aimed at treating or preventing diseases through microbial modulation.
Pueraria lobata (kudzu) is used in traditional medicine for cardiovascular issues, menopause, and alcohol dependence due to its bioactive isoflavones. These compounds, particularly puerarin, offer vasodilatory effects and antioxidant properties, enhancing blood circulation and reducing oxidative stress.
Pueraria Flower Extract (PFE) addresses microbial imbalances and inflammation in endometriosis, validating its role as a microbiome-targeted therapy.
Metronidazole is a validated microbiome-targeted intervention (MBTI) for endometriosis, reducing key dysbiotic taxa and suppressing inflammation and lesion progression.
Metformin is a synthetic derivative of guanidine derived from the guanidine alkaloid of the plant Galega officinalis L. with significant hypoglycemic effects. It is a first-line antihyperglycemic agent due to its efficacy, low cost, and favorable safety profile.
By directly targeting microbial dysbiosis, hormonal imbalances, and inflammation, metformin not only validates the clinical relevance of the endometriosis microbiome signature but also positions itself as an effective therapeutic option for the condition.
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
A low-nickel diet is validated as an MBTI for endometriosis because it disrupts nickel-dependent pathogens, rebalances the microbiome, and improves symptoms like pelvic pain and dysmenorrhea.
Hyperbaric Oxygen Therapy (HBOT) involves breathing pure oxygen in a pressurized chamber, which increases the amount of oxygen dissolved in the blood and delivered to tissues.
HBOT demonstrates complete remission and holds significant promise as a candidate for microbiome-targeted intervention for endometriosis.
Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein classified as a postbiotic with immunomodulatory, antimicrobial, and prebiotic-like properties.
Transvaginal photobiomodulation (TVPBM) is an emerging therapeutic modality that uses light therapy to address various gynecological and pelvic health issues. This treatment is noninvasive and uses specific wavelengths of light to stimulate cellular functions, promoting healing and reducing inflammation.
Vaginal Microbiome Transplant (VMT) involves transferring healthy vaginal flora from a donor to a recipient to treat conditions like recurrent bacterial vaginosis. It aims to restore balance in the vaginal microbiome, potentially offering a non-pharmacological treatment option for persistent gynecological disorders.
Fecal Microbiota Transplantation (FMT) involves transferring fecal bacteria from a healthy donor to a patient to restore microbiome balance.
Flavones and flavonols are plant-derived compounds known for their antioxidant, anti-inflammatory, and antimicrobial properties.
Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein classified as a postbiotic with immunomodulatory, antimicrobial, and prebiotic-like properties.
Gallium is studied for its unique antimicrobial and anticancer properties. It inhibits metalloproteinases, disrupts bacterial iron metabolism, and may enhance antibiotic efficacy, particularly against resistant strains. Gallium compounds show potential as non-traditional therapeutic agents in treating infections and inhibiting cancer cell invasion and metastasis.
Gallium is studied for its unique antimicrobial and anticancer properties. It inhibits metalloproteinases, disrupts bacterial iron metabolism, and may enhance antibiotic efficacy, particularly against resistant strains. Gallium compounds show potential as non-traditional therapeutic agents in treating infections and inhibiting cancer cell invasion and metastasis.
Clinoptilolite zeolite binds nickel ions, reducing pathogen activity, making it a potential therapy for nickel allergies and nickel-induced microbiome imbalances.
A STOP (Suggested Termination Of Practices) is a recommendation that advocates for the discontinuation of certain medical interventions, treatments, or practices based on emerging evidence indicating that these may be ineffective, harmful, or counterproductive in the management of specific conditions.
Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein classified as a postbiotic with immunomodulatory, antimicrobial, and prebiotic-like properties.
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.
Matrix Metalloproteinases (MMPs) are zinc-dependent enzymes that regulate extracellular matrix remodeling, with critical roles in health, disease, and interactions with the microbiome.
Estrogen is a steroid hormone primarily found in women, crucial for reproductive health, secondary sexual characteristics, and various physiological processes. It regulates menstrual cycles, supports pregnancy, and influences bone density and cardiovascular health. Dysregulation of estrogen levels can lead to various disorders and health complications.
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
Vaginal Microbiome Transplant (VMT) involves transferring healthy vaginal flora from a donor to a recipient to treat conditions like recurrent bacterial vaginosis. It aims to restore balance in the vaginal microbiome, potentially offering a non-pharmacological treatment option for persistent gynecological disorders.
Fecal Microbiota Transplantation (FMT) involves transferring fecal bacteria from a healthy donor to a patient to restore microbiome balance.
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A More Diverse Cervical Microbiome Associates with Better Clinical Outcomes in Patients with Endometriosis: A Pilot Study.Biomedicines. Jan 14, 2022
Read ReviewClinicalTrials.gov ID NCT03481842
Safety, Tolerability and Efficacy of Vaginal Suppositories for Treatment of the Endometriosis (ELTA)BioGene Pharmaceutical Ltd. Last Update Posted October 29, 2021
Teworte S, Aleandri S, Weber JR, Carone M, Luciani P. Mucoadhesive
3D printed vaginal ovules to treat endometriosis and fibrotic uterine diseases.Eur J Pharm Sci. 2023
Zipper R, Pryor B, Lamvu G.
Transvaginal Photobiomodulation for the Treatment of Chronic Pelvic Pain: A Pilot Study.Womens Health Rep (New Rochelle). November 23, 2021
Abbe C, Mitchell CM.
Bacterial vaginosis: a review of approaches to treatment and prevention.Front Reprod Health. May 31, 2023
Qin R, Tian G, Liu J, Cao L.
The gut microbiota and endometriosis: From pathogenesis to diagnosis and treatment.https://doi.org/10.3389/fcimb.2022.1069557
Quaranta G, Sanguinetti M, Masucci L.
Fecal Microbiota Transplantation: A Potential Tool for Treatment of Human Female Reproductive Tract Diseases.Front Immunol. November 26, 2019
P D Gupta, K Pushkala.
FMT as an Effective Therapeutic Agent for EndometriosisJournal of Clinical and Medical Case Reports and Reviews. July 30, 2022
Guo C, Zhang C.
Role of the gut microbiota in the pathogenesis of endometriosis: a review.Front Microbiol. March 5, 2024
Samaneh Y, ShahidehJahanian S, Azadeh M, Anoshirvan K.
The association of food consumption and nutrient intake with endometriosis risk in Iranian women: A case-control study.Int J Reprod Biomed. 2019
Pereira FEXG, Medeiros FDC, Rocha HAL, Silva KSD.
Effects of omega-6/3 and omega-9/6 nutraceuticals on pain and fertility in peritoneal endometriosis in rats.Acta Cir Bras. 2019
Harris, H. R., Eke, A. C., Chavarro, J. E., & Missmer, S. A.
Harris, H. R., Eke, A. C., Chavarro, J. E., & Missmer, S. A. (2018). Fruit and vegetable consumption and risk of endometriosis. Human Reproduction, 33(4), 715–727. doi:10.1093/humrep/dey014Journal of Human Reproduction. 2018.
Read ReviewKim KH, Park JK, Choi YW, et al.
Hexane extract of aged black garlic reduces cell proliferation and attenuates the expression of ICAM-1 and VCAM‑1 in TNF-α-activated human endometrial stromal cells.Int J Mol Med. (2013)
Gao JJ, Hu YW, Wang YC, et al.
ApoM Suppresses TNF-α-Induced Expression of ICAM-1 and VCAM-1 Through Inhibiting the Activity of NF-κB.DNA Cell Biol. (2015)
Thomson M, Ali M.
Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent.Curr Cancer Drug Targets. 2003
Kolahdouz Mohammadi R, Arablou T
Resveratrol and endometriosis: In vitro and animal studies and underlying mechanisms (Review).Biomed Pharmacother. 2017
Dull AM, Moga MA, Dimienescu OG, Sechel G, Burtea V, Anastasiu CV.
Therapeutic Approaches of Resveratrol on Endometriosis via Anti-Inflammatory and Anti-Angiogenic Pathways.Molecules. 2019
Jiang T, Chen Y, Gu X, et al.
Review of the Potential Therapeutic Effects and Molecular Mechanisms of Resveratrol on Endometriosis.Int J Womens Health. 2023
Psilopatis I, Vrettou K, Fleckenstein FN, Theocharis S.
The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities.Cells. 2023
Huang, Y., Wei, Y., Liang, F. et al.
Exploring the link between dietary zinc intake and endometriosis risk: insights from a cross-sectional analysis of American womenBMC Public Health (2024)
Read ReviewHarris, H. R., Eke, A. C., Chavarro, J. E., & Missmer, S. A.
Harris, H. R., Eke, A. C., Chavarro, J. E., & Missmer, S. A. (2018). Fruit and vegetable consumption and risk of endometriosis. Human Reproduction, 33(4), 715–727. doi:10.1093/humrep/dey014Journal of Human Reproduction. 2018.
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