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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).
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. [20] 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.
High iron levels from retrograde menstruation promote pathogenic bacteria, lesion growth, inflammation, and oxidative stress.[21] Studies suggest that nickel sensitivity affects 90.3% of patients, or possibly even more [22], and that a Low-nickel diet (LNiD) shows significant clinical benefits. [23] 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 (MMPs), which are implicated in endometriotic lesion invasion.[24]Metalloestrogens like cadmium, nickel, and lead increase oxidative stress, inflammation, and estrogenic activity. [25] These findings highlight the role that the metallomic signature plays in the condition, and the potential of chelation therapies, dietary modifications, and reduced heavy metal exposures for managing or preventing endometriosis.
| Metal | Findings |
|---|---|
| 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.[27] 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. [28] |
| 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). [29][30] Nickel’s classification as a metalloestrogen highlights its estrogen-mimicking capabilities, contributing to hormonal dysregulation in endometriosis. [31] 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. [33] 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. [34] 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. [35][36] |
| 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. [37][38][39] |
| 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. [40] |
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. u003csupu003e[u003ca href=u0022https://doi.org/10.3389/fcimb.2021.788836u0022u003exu003c/au003e]u003c/supu003e 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.rnrnConsider that u003ca href=u0022https://microbiomesignatures.com/definition/estrogen/u0022u003eestrogenu003c/au003e appears to mediate the microbiome as much as the microbiome mediates estrogen. u003csupu003e[u003ca href=u0022https://doi.org/10.1093/biolre/ioac147u0022u003exu003c/au003e]u003c/supu003e
Diet is a key modulator of the microbiome, with different dietary patterns influencing microbial composition and function. While a u003ca href=u0022https://microbiomesignatures.com/interventions/low-nickel-diet/u0022u003elow-nickel dietu003c/au003e alone can have a substantial impact, additional interventions such as probiotics, prebiotics, u003ca href=u0022https://microbiomesignatures.com/definition/vaginal-microbiome-transplant-vmt/u0022u003eVMTu003c/au003e and u003ca href=u0022https://microbiomesignatures.com/definition/fecal-microbiota-transplantation-fmt/u0022u003eFMTu003c/au003e 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.
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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.
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Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
Did you know?
Gut microbiota predict endometriosis better than vaginal microbiota.
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Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
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).
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Lorem ipsum dolor sit amet, consectetur adipiscing elit. Proin ut laoreet tortor. Donec euismod fermentum pharetra. Nullam at tristique enim. In sit amet molestie
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Lorem ipsum dolor sit amet, consectetur adipiscing elit. Proin ut laoreet tortor. Donec euismod fermentum pharetra. Nullam at tristique enim. In sit amet molestie
Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
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.
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.
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.
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.
Matrix Metalloproteinases (MMPs) are zinc-dependent enzymes that regulate extracellular matrix remodeling, with critical roles in health, disease, and interactions with the microbiome.
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
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.
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.
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Oral-microbiome-derived signatures enable non-invasive diagnosis of laryngeal cancers.J Transl Med. July 15, 2023.
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Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies.Med. October 3, 2024.
Read ReviewMori-Yamanaka K, Kimura F, Nakamura A, Hanada T, Kitazawa J, Morimune A, Tsuji S, Murakami T.
Exploratory Study of Serum Lactoferrin and Anti-Lactoferrin Antibody Concentrations in Patients with Endometriosis.Tohoku J Exp Med. 2023.
Read ReviewWyatt J, Fernando SM, Powell SG, et al.
The role of iron in the pathogenesis of endometriosis: a systematic review.Hum Reprod Open. (Jul 27, 2023 )
Read ReviewZurawin RK, Zurawin JL.
Adverse events due to suspected nickel hypersensitivity in patients with essure micro-inserts.Minim Invasive Gynecol. 2011
Borghini R, Porpora MG, Casale R, Marino M, Palmieri E, Greco N, Donato G, Picarelli A.
Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot Study.Nutrients. 2020
Read ReviewHuang, 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 ReviewOsuchowska-Grochowska et al.
Brief Review of Endometriosis and the Role of Trace Elements.International Journal of Molecular Sciences.
Read ReviewWyatt J, Fernando SM, Powell SG, et al.
The role of iron in the pathogenesis of endometriosis: a systematic review.Hum Reprod Open. (Jul 27, 2023 )
Wyatt J, Fernando SM, Powell SG, et al.
The role of iron in the pathogenesis of endometriosis: a systematic review.Hum Reprod Open. (Jul 27, 2023 )
Read ReviewBradley, Justin M et al.
Bacterial iron detoxification at the molecular level.Journal of Biological Chemistry. (December, 2020)
Read ReviewBorghini R, Porpora MG, Casale R, et al.
Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot Study.Nutrients. (Jan 28, 2020)
Read ReviewYuk JS, Shin JS, Shin JY, Oh E, Kim H, Park WI.
Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study.PLoS One. October 6, 2015.
Read ReviewSilva, N. & Senanayake, Hemantha & Peiris-John, Roshini & Wickremasinghe, Rajitha & Sathiakumar, Nalini & Waduge, Vajira.
Presence of metalloestrogens in ectopic endometrial tissue.J Pharm Biomed Sci. 2012
Read ReviewAquino NB, Sevigny MB, Sabangan J, Louie MC.
The role of cadmium and nickel in estrogen receptor signaling and breast cancer: metalloestrogens or not?J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. (September 12, 2012)
Borghini R, Porpora MG, Casale R, et al.
Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot Study.Nutrients. (Jan 28, 2020)
Read ReviewSilva, N. & Senanayake, Hemantha & Peiris-John, Roshini & Wickremasinghe, Rajitha & Sathiakumar, Nalini & Waduge, Vajira.
Presence of metalloestrogens in ectopic endometrial tissue.J Pharm Biomed Sci. 2012
Read ReviewKim M-G, Min Y-S, Ahn Y-S.
Does Exposure of Lead and Cadmium Affect the Endometriosis?International Journal of Environmental Research and Public Health. 2021
Read ReviewOsuchowska-Grochowska, Ida & Blicharska, Eliza & Gogacz, Marek & Nogalska, Agata & Winkler, Izabela & Szopa, Agnieszka & Ekiert, Halina & Tymczyna-Borowicz, Barbara & Rahnama-Hezavah, Mansur & Grochowski, Cezary.
Brief Review of Endometriosis and the Role of Trace Elements.International Journal of Molecular Sciences.
Read ReviewSilva, N. & Senanayake, Hemantha & Peiris-John, Roshini & Wickremasinghe, Rajitha & Sathiakumar, Nalini & Waduge, Vajira.
Presence of metalloestrogens in ectopic endometrial tissue.J Pharm Biomed Sci. 2012
Read ReviewKim M-G, Min Y-S, Ahn Y-S.
Does Exposure of Lead and Cadmium Affect the Endometriosis?International Journal of Environmental Research and Public Health. 2021
Read ReviewOsuchowska-Grochowska, Ida & Blicharska, Eliza & Gogacz, Marek & Nogalska, Agata & Winkler, Izabela & Szopa, Agnieszka & Ekiert, Halina & Tymczyna-Borowicz, Barbara & Rahnama-Hezavah, Mansur & Grochowski, Cezary.
Brief Review of Endometriosis and the Role of Trace Elements.International Journal of Molecular Sciences.
Read ReviewHuang, 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 ReviewSalliss ME, Farland LV, Mahnert ND, Herbst-Kralovetz MM.
The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain.Hum Reprod Update. (2021)
Read ReviewUzuner C, Mak J, El-Assaad F, Condous G.
The bidirectional relationship between endometriosis and microbiome.Front Endocrinol (Lausanne). Mar 7, 2023
Read ReviewChang CY, Chiang AJ, Lai MT, et al.
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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