Endometriosis — WikiBiome

A complete internal pelvic reproductive model has four small dark superficial foci, two on one ovary and two on nearby peritoneal tissue. — **Internal pelvic anatomy reconstruction** Editorially reviewed
Internal pelvic orientation with four representative ectopic-tissue foci for endometriosis. The foci are editorial representations, not observed patient lesions, a universal distribution, stage, severity, fertility outcome, or diagnosis.
WikiBiome / Microbiome MedicineNLM-MeSH-condition-, NICHD-pelvic-distribution-, four-focus-, and literal-output-audit-informed reconstruction
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Subject
Endometriosiscondition
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MeSH:D004715
Review
Editorial review completeIdentifiers authority-verified · Accessibility validated · 2026-09-06 · endometriosis|endometriosis-pathology-v1.webp
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Trained-algorithmic mediaCreated with a trained generative algorithm and reviewed by WikiBiome for subject identity, scientific framing, identifiers, provenance, and accessibility.
Scientific basis
Endometriosis — MeSH What is endometriosis?
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CC BY-SA 4.0Created 2026-09-06

Endometriosis is a chronic estrogen-dependent inflammatory condition affecting approximately 10% of reproductive-age women, characterized by the growth of endometrial-like tissue outside the uterus.^{[1]Gut and Vaginal Microbiota in the Endometriosis: Systematic Review and Meta-AnalysisColonetti T, Saggioratto MC, Grande AJ et al. · 2023Open reference 1 ↓} The conventional framing treats it as a hormonal or immune disorder.^{[2]Current Updates on the Role of Microbiome in Endometriosis: A Narrative ReviewSer HL, Au Yong SJ, Shafiee MN et al. · 2023Open reference 2 ↓}

The metallomic and microbiome perspective—developed most comprehensively in the companion signature page—reveals it as an ecological disease driven by metal-dependent microbial communities.

This entity page provides the broader metallomics context: the systemic metal exposures, dietary paradoxes, and environmental links that feed the disease ecology described in the signature.

The pioneering finding is the extraordinary prevalence of nickel allergy in endometriosis patients: 90.3% tested positive for nickel allergic contact mucositis (nickel (Ni) ACM) in the^{[3]Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot StudyBorghini R, Porpora MG, Casale R et al. · 2020Open reference 3 ↓} study—a prevalence far exceeding the general population rate of approximately 30%.

Evidence map37 cited passagesInspect provenance +

Introduction

Endometriosis is a chronic estrogen-dependent inflammatory condition affecting approximately 10% of reproductive-age women, characterized by the growth of endometrial-like tissue outside the uterus. The conventional framing treats it as a hormonal or immune disorder. The metallomic and microbiome perspective—developed most comprehensively in the companion

Introduction

The pioneering finding is the extraordinary prevalence of nickel allergy in endometriosis patients: 90.3% tested positive for nickel allergic contact mucositis (Ni ACM) in the study—a prevalence far exceeding the general population rate of approximately 30%.

Gut Microbiome Connection

Metal-dependent pathogenic consortium. The enriched taxa (E. coli, B. fragilis, S. agalactiae, F. nucleatum, C. albicans) share a common feature: dependence on nickel, iron, and zinc for virulence enzymes. In the cervicovaginal niche, Gardnerella is enriched in endometriosis patients (67.7% vs 36.8% of non-Lactobacillus taxa in sensitivity analysis) and its

Gut Microbiome Connection

Estrobolome dysbiosis. Beta-glucuronidase-producing taxa (E. coli, B. fragilis, S. agalactiae) deconjugate estrogen glucuronides, driving hepatic estrogen recirculation that fuels the estrogen-dependent disease progression.

Gut Microbiome Connection

SCFA producer loss. Lachnospiraceae and Ruminococcus are depleted because they lack robust efflux pumps to survive the metal-rich, pro-inflammatory environment. Their loss causes colonocyte dysfunction, intestinal permeability, and microbial translocation—perpetuating the disease cycle.

Gut Microbiome Connection

Environmental Metal Exposure Links

documented dramatically elevated peritoneal fluid metals in an endometriosis patient following a vegetarian diet with no occupational exposure. The case is instructive: the patient's lacto-ovo vegetarian diet rich in tomatoes, hazelnuts, walnuts, almonds, and olive oil provided a high-nickel dietary load that accumulated in the peritoneal environment.

The Plant-Based Diet Paradox

reviewed evidence that plant-based diets reduce circulating estrogen by 10-25% through increased fiber, which should benefit this estrogen-dependent disease. A low-fat vegan diet increased sex-hormone binding globulin and reduced dysmenorrhea severity. Yet the plant-based foods recommended—legumes, whole grains, nuts, soy, leafy greens—are among the hi

The Zinc-MMP Tissue Invasion Paradox

found that higher dietary zinc intake (14 mg/day) was associated with a 60% increased odds of endometriosis (OR 1.6, 95% CI 1.12-2.27) in NHANES data (4,315 women). This is counterintuitive given zinc's antioxidant and anti-inflammatory roles. The resolution lies in the dual nature of zinc in endometriosis:

The H2S/NF-kB Amplification Loop

demonstrated that hydrogen sulfide promotes endometrial stromal cell proliferation via NF-kB activation. CBS and CSE (H2S-producing enzymes) are overexpressed in ectopic endometrium. NF-kB is also activated by nickel exposure in allergic contact mucositis. This creates a convergent pathway: dietary nickel activates NF-kB in the gut mucosa; H2S from endometri

Introduction

This is the first disease signature fully analyzed using the Karen's Brain pipeline, presented at the Amsterdam Endometriosis Conference by karen pendergrass. The signature has been validated and expanded with data from 27 additional peer-reviewed papers spanning microbiome profiling, metabolomics, multi-site sequencing, and meta-analyses.

Metallomic Signature

The tissue metallomic signature in endometriosis is characterized by elevated zinc, iron, cadmium, lead, and nickel. Cross-referencing 27 additional papers confirms this with quantified consensus frequencies:

Environmental Exposures

Brassica vegetables are cadmium, lead, zinc, and nickel hyperaccumulators—and increased brassica consumption was found as a risk factor for endometriosis, consistent with the metallomic signature.

Nutritional Immunity Response

The host is actively fighting the metal/microbial imbalance. All of the following are elevated in endometriosis:

Mis-metallation Events

Cadmium and lead both enter cells through calcium channels, displacing correct cofactors like zinc or iron (Primitive 3: Mis-metallation and Toxic Metal Entry). When cadmium and lead are combined in the environment, they produce a synergistic effect generating even more oxidative stress and hypoxia than either metal alone.

Virulence Enzymes and Features

Key insight: Glyoxalase is the enzyme that allows pathogens to evade neutrophils in the bloodstream. It is nickel-dependent. Remove the nickel, and you disable this evasion mechanism across all glyoxalase-positive pathogens simultaneously.

Interkingdom Relationships

candida albicans is NOT an incidental finding and is NOT noise—it is a critical component of the disease ecology that 16S studies fail to detect (Primitive 6: Interkingdom Relationships and Functional Shielding).

Introduction

The pioneering finding is the extraordinary prevalence of nickel allergy: 90.3% of symptomatic endometriosis patients tested positive for nickel allergic contact mucositis (Ni ACM) (, open-label pilot, n=31). Peritoneal fluid metal analysis revealed dramatically elevated nickel (4:1 ratio vs control), lead (90:1 ratio), and bismuth (1.5:1 ratio) even in pati

Metallomic Signature

| Metal | Evidence | Confidence | |-------|----------|------------| | nickel | Peritoneal fluid 40.4 ug/L vs <LOD in control (4:1 ratio); 77.8% literature consensus; Ni ACM prevalence 90.3% in symptomatic patients (; ) | High | | iron | Elevated in peritoneal fluid via retrograde menstruation; 70.4% literature consensus; hepcidin elevation indicates function

Metallomic Signature

The nickel-estrogen convergence. Cadmium binds ERa with affinity near estradiol, activating classical estrogen target genes (, expert opinion). Nickel acts via noncompetitive ERa binding and epigenetic mechanisms (histone deacetylation, H3K9 methylation). Both are classified as metalloestrogens, and both accumulate in the peritoneal environment where endomet

Environmental Exposures

Diet (largest contributor): Nickel, zinc, iron, cadmium, lead through plant-based foods, nuts, legumes, whole grains. A lacto-ovo vegetarian patient with no occupational exposure showed dramatically elevated peritoneal metals ()

Environmental Exposures

Retrograde menstruation: Iron exposure to the peritoneal microenvironment; LPS-contaminated menstrual blood drives cyclical inflammation ()

Environmental Exposures

Brassica vegetables: Cadmium, lead, zinc, and nickel hyperaccumulators; increased brassica consumption identified as an endometriosis risk factor ()

Environmental Exposures

The plant-based diet paradox. Plant-based diets reduce circulating estrogen by 10-25% through increased fiber (, prospective cohort review), which should benefit this estrogen-dependent disease. Yet the recommended foods—legumes, whole grains, nuts, soy—are among the highest-nickel foods. For the 90.3% of patients with nickel sensitivity, standard plan

Showing 24 of 37 evidence-bearing passages. Every remaining citation is still indexed in the reference record below.

Integrated microbiome signature

One disease. Five evidence layers.

A generated systems view of the metals, organisms, host sequestration signals, ecological conditions, and microbial functions indexed for Endometriosis.

Evidence layer

Metallomic signature

Elements and antioxidants reported as elevated, accumulated, depleted, or systemically altered.

high confidence

↑

Elevated or accumulated

Zinc Iron Cadmium Lead Nickel Copper Bismuth

↓

Depleted or redistributed

Glutathione (GSH)

Evidence layer

Taxonomic signature

Organisms reported as enriched or depleted, with their indexed functional context kept beside the name.

moderate confidence

Enriched taxa8

Escherichia coli

Primary pathobiont -- siderophore-mediated iron acquisition, LPS/TLR4 activation, beta-glucuronidase-driven estrogen deconjugation; LPS 4-6x higher in menstrual fluid of patients

Bacteroides fragilis

zinc (Zn)-dependent BFT toxin cleaves E-cadherin; beta-glucuronidase activity drives estrogen recirculation; iron piracy via siderophores

Streptococcus agalactiae

Group B Strep — zinc (Zn)/nickel (Ni) critical cofactors, beta-glucuronidase positive, iron piracy

Fusobacterium nucleatum

zinc (Zn)/nickel (Ni)-dependent enzymes, oxygen consumption creating local hypoxia, NOT involved in estrogen deconjugation

Candida albicans

Interkingdom biofilm partner; oxygen consumption creates anaerobic niches; functional shielding of bacterial pathogens; increased biomass in presence of nickel

Gardnerella

Enriched in cervicovaginal niche (67.7% vs 36.8% of non-Lactobacillus taxa); sialidase-driven mucus degradation facilitates pathobiont colonization

Streptococcus

Enriched in cervical microbiota; beta-glucuronidase-producing species contribute to estrogen recirculation

Blautia

Abundance positively correlated with serum estradiol; beta-glucuronidase activity links to estrobolome dysbiosis

Depleted taxa5

Lactobacillus

Enriched in gut/peritoneum but DEPLETED in vaginal cavity — translocation likely; nickel-dependent, glyoxalase-positive

Lachnospiraceae

SCFA producers — lost competitive advantage in iron-rich pro-inflammatory environment

Ruminococcus

Decreased in endometriosis; fecal calprotectin correlated with Ruminococcus abundance suggesting inflammatory displacement

Lachnospiraceae (Family)

SCFA producers -- lost competitive advantage in metal-rich, pro-inflammatory environment; Lachnospira significantly decreased in stage 3/4 patients

Roseburia

SCFA producer depleted in endometriosis gut; lacks robust efflux pumps to survive metal-rich environment

Evidence layer

Nutritional immunity

Host metal-withholding, inflammatory, antioxidant, and microbial-metabolite signals indexed in the signature.

moderate confidence

↑

Elevated host signals

Calprotectin (S100A8/A9)Lactoferrin Transferrin Hepcidin Lipocalin-2

↓

Depleted protective signals

Glutathione (GSH)

Evidence layer

Ecological state

The environmental conditions that connect the organism-level observations into a system.

moderate confidence

WB.ECO / SYSTEM MODEL8 connected states

Hypoxiaindexed ecological state

Biofilmindexed ecological state

Estrogen Recirculationindexed ecological state

Functional Shieldingindexed ecological state

Fermentative Metabolismindexed ecological state

Acidic Microenvironmentindexed ecological state

LPS TLR4 NF KB Loopindexed ecological state

H2S NF KB Amplificationindexed ecological state

Evidence layer

Virulence functions

Microbial structures, enzymes, and acquisition systems implicated by the linked evidence.

moderate confidence

Zinc-Metalloprotease NiFe-Hydrogenase Nickel-Urease Nickel-Glyoxalase Beta-Glucuronidase SiderophoresSialidaseBFT Fragilysin

Encyclopedia article

The disease record, in full.

The original WikiBiome disease narrative remains intact beneath the generated signature atlas.

Metallomic Signature#

The tissue metallomic signature from the endometriosis signature page shows elevated zinc, iron, cadmium, lead, and nickel with depleted glutathione. From the peritoneal fluid data:

Metal	Peritoneal Fluid Finding	Systemic Relevance
[[nickel	nickel (Ni)]]	40.4 ug/L vs. <LOD in control (4:1 ratio); 77.8% literature consensus	Cofactor for Urease, glyoxalase, Hydrogenase in pathogenic taxa; nickel ACM prevalence 90.3% in symptomatic patients
[[iron	iron (Fe)]]	Elevated in peritoneal fluid via retrograde menstruation	70.4% literature consensus; siderophore competition; functional anemia via hepcidin (host defense, NOT deficiency)
[[lead	lead (Pb)]]	75 ug/L vs. 0.72 ug/L in control (90:1 ratio)	59.3% consensus; mis-metallation via calcium (Ca) channels; synergistic with cadmium (Cd) for Oxidative Stress
[[cadmium	cadmium]]	Elevated in peritoneal environment	18.5% consensus; metalloestrogen (ERa binding); synergistic with lead
[[zinc	zinc (Zn)]]	Elevated locally (lesion microenvironment)	14.8% consensus; MMP cofactor enabling tissue invasion; calprotectin target
[[copper	copper (Cu)]]	Elevated	14.8% consensus; microbial virulence cofactor

The Hepcidin Signal: Functional Anemia vs. True Deficiency#

A critical clinical insight from the signature analysis: hepcidin is elevated in endometriosis, indicating the body is deliberately withholding iron from pathogens. Low serum iron in endometriosis patients represents a host defense strategy (functional anemia), not a nutritional deficiency.

This has direct therapeutic implications—iron supplementation may be counterproductive (see STOPs below).

Gut Microbiome Connection#

The microbiome dimension of endometriosis is extensively documented in the signature page. Key elements relevant to the metallomic context:

Metal-dependent pathogenic consortium. The enriched taxa (E. coli, B. fragilis, S. agalactiae, F. nucleatum, C. albicans) share a common feature: dependence on nickel, iron, and zinc for virulence enzymes.^{[4]Associations Between Endometriosis and Gut MicrobiotaSvensson A, Brunkwall L, Roth B et al. · 2021Open reference 4 ↓}^{[5]The Endobiota Study: Comparison of Vaginal, Cervical and Gut Microbiota Between Women with Stage 3/4 Endometriosis and Healthy ControlsAta B, Yildiz S, Turkgeldi E et al. · 2019Open reference 5 ↓}

In the cervicovaginal niche, *Gardnerella* is enriched in endometriosis patients (67.7% vs 36.8% of non-Lactobacillus taxa in sensitivity analysis) and its sialidase-driven mucus degradation may facilitate pathobiont colonization.^{[5]The Endobiota Study: Comparison of Vaginal, Cervical and Gut Microbiota Between Women with Stage 3/4 Endometriosis and Healthy ControlsAta B, Yildiz S, Turkgeldi E et al. · 2019Open reference 5 ↓} Nickel-dependent glyoxalase enables immune evasion across all glyoxalase-positive pathogens. Iron-dependent siderophores power biofilm formation.

Zinc-dependent metalloproteases enable tissue invasion.

Estrobolome Dysbiosis. Beta-glucuronidase-producing taxa (E. coli, B. fragilis, S. agalactiae) deconjugate estrogen glucuronides, driving hepatic estrogen recirculation that fuels the estrogen-dependent disease progression.^{[6]Gut microbiome in endometriosis: a cohort study on 1000 individualsPerez-Prieto I, Vargas E, Salas-Espejo E et al. · 2024Open reference 6 ↓}^{[7]The bidirectional relationship between endometriosis and microbiomeUzuner C, Mak J, El-Assaad F et al. · 2023Open reference 7 ↓}

SCFA producer loss. Lachnospiraceae and Ruminococcus are depleted because they lack robust efflux pumps to survive the metal-rich, pro-inflammatory environment.^{[8]Gut microbiota imbalance and its correlations with hormone and inflammatory factors in patients with stage 3/4 endometriosisShan J, Ni Z, Cheng W et al. · 2021Open reference 8 ↓}^{[9]Ni 2020 — Fecal Metabolomics and Gut Microbiota Correlation in Endometriosis MiceZhexin Ni, Shuai Sun, Yanli Bi et al. · 2020Open reference 9 ↓} Their loss causes colonocyte dysfunction, intestinal permeability, and microbial translocation—perpetuating the disease cycle.

Candida functional shielding. C. albicans biofilms consume oxygen (creating anaerobic niches for obligate anaerobes), shield bacteria from immune detection, and show increased biomass in the presence of nickel.^{[10]Bacterial contamination hypothesis: a new concept in endometriosisKhan KN, Fujishita A, Hiraki K et al. · 2018Open reference 10 ↓}

Environmental Metal Exposure Links#

^{[11]Elevated Lead, Nickel, and Bismuth Levels in the Peritoneal Fluid of a Peritoneal Endometriosis Patient without Toxic Habits or Occupational Exposure following a Vegetarian DietLopez-Botella A, Gomez-Torres MJ, Sanchez R et al. · 2023Open reference 11 ↓} documented dramatically elevated peritoneal fluid metals in an endometriosis patient following a vegetarian diet with no occupational exposure.

The case is instructive: the patient's lacto-ovo vegetarian diet rich in tomatoes, hazelnuts, walnuts, almonds, and olive oil provided a high-nickel dietary load that accumulated in the peritoneal environment.

Sources of the metal burden include. Diet (largest contributor): zinc (Zn), iron (Fe), nickel (Ni), cadmium (Cd), lead (Pb) through plant-based foods, nuts, legumes, whole grains. Brassica vegetables: Cadmium, lead, zinc, and nickel hyperaccumulators; increased brassica consumption was found as a risk factor for endometriosis.

Retrograde menstruation: iron exposure to the peritoneal microenvironment.

Smoking: cadmium, lead, nickel. Stainless steel cookware: nickel, chromium (Cr), iron. Cosmetics: lead, nickel, cadmium.

Dietary Metal Paradoxes#

Full evidence is maintained on the canonical paradox articles.

The Plant-Based Diet / Nickel TrapAnti-inflammatory and plant-forward diets are the standard nutritional recommendation for endometriosis, PCOS, rheumatoid arthritis, and IBD. These diets emphasize legumes, whole grains, nuts, seeds, dark choco

Read paradox →02

The Zinc-Endometriosis ReversalZinc is depleted in nearly every disease state examined in this wiki -- cancer (breast, prostate, lung, pancreatic, esophageal, colorectal), type 2 diabetes, PCOS, autism, postpartum depression, and IBD. Zinc s

Read paradox →03

The H2S/NF-kB Amplification Loopdemonstrated that hydrogen sulfide promotes endometrial stromal cell proliferation via NF-kB activation. CBS and CSE (H2S-producing enzymes) are overexpressed in ectopic endometrium. NF-kB is also activated by

Read paradox →

Developmental Vulnerability#

Endometriosis onset typically occurs during adolescence and early reproductive years, a period of high estrogen activity and ongoing reproductive tract development. Prenatal and pubertal exposure to metalloestrogens (cadmium (Cd), nickel (Ni)) during these windows may prime susceptibility.

No studies have evaluated chronic low-dose metalloestrogen exposure during puberty specifically in relation to endometriosis risk—this remains a critical gap. See Developmental Metal Vulnerability: Critical Windows of Susceptibility.

Current Interventions with Metal Relevance#

Validated (from signature page)#

Intervention	Mechanism
Low-Nickel Diet	Disables nickel (Ni)-dependent glyoxalase, urease, hydrogenase; reduces Candida co-aggregate biofilm biomass; all 15 GI, 7 extra-intestinal, and 3 gynecological symptoms improved significantly
Low-Red-Meat Diet for Endometriosis	Reduces free iron and zinc available to pathogens
Low-Fat Diet for Endometriosis	Reduces E. coli growth; lowers circulating estrogen by 10-25%
E. coli Nissle 1917	Outcompetes pathogenic E. coli via superior siderophore systems; lacks virulence genes
Saccharomyces boulardii	Outcompetes Candida; cell walls bind cadmium and lead
Lactoferrin Supplementation (Cross-Condition)	Supports nutritional immunity; chelates iron + nickel from pathogens; alternative to iron supplementation
NAC supplementation	Replenishes depleted glutathione—the only factor neutralizing cadmium (Cd) and lead (Pb)

STOPs#

STOP	Rationale
Iron supplementation	Hepcidin elevation = functional anemia (host defense). Iron feeds siderophore-producing pathogens.
Zinc supplementation	Calprotectin is already sequestering zinc as host defense. Zinc feeds MMP-producing pathogens.

Open Questions#

Unresolved questions identified by the current evidence record.

01Nickel allergy as diagnostic tool: Should nickel (Ni) ACM testing (nickel omPT) become standard in the endometriosis workup, given 90.3% prevalence in symptomatic patients?