Karen Pendergrass, Standards Team

A low-nickel diet significantly reduced GERD symptoms in 95% of participants, regardless of patch test status. The results suggest dietary nickel may contribute to GERD pathophysiology independently of classical allergy mechanisms.

Nickel allergic contact mucositis was identified in over 90% of endometriosis patients with IBS-like symptoms. A low-nickel diet significantly reduced gastrointestinal, extra-intestinal, and gynecological symptoms, revealing nickel sensitivity as a key driver of endometriosis symptomatology.

What was studied?This pilot study evaluated the prevalence of nickel (Ni) allergy in individuals diagnosed with irritable bowel syndrome (IBS) and investigated the clinical efficacy of a low-nickel diet (LNiD) in this population. Specifically, the authors assessed the impact of the dietary intervention on gastrointestinal symptoms, intestinal permeability, quality of life, and psychological status in […]

This review highlights the safety and efficacy of phage therapy for chronic and prosthetic joint infections, showing a 91% success rate. Targeted pathogens include P. aeruginosa and S. aureus, key MMAs in wound microbiomes, underscoring phages as viable interventions for biofilm-associated, drug-resistant infections.

Tinidazole shows strong alignment with endometriosis microbiome signatures by targeting MMAs such as Prevotella and Fusobacterium. Its pharmacological profile and potential for microbial realignment make it a compelling candidate for fast-tracked translational research and microbiome-targeted intervention.

OverviewThe Research Fast-Track (RFT) designation is a priority label used within the Microbiome Signatures framework to identify microbiome-targeted interventions that demonstrate exceptional translational potential and clinical relevance. This designation highlights interventions that warrant accelerated research, validation, and collaborative exploration due to their alignment with condition-specific microbiome signatures and their capacity to impact disease pathogenesis or […]

This study demonstrates that peritoneal fluid-to-plasma ferritin and lactoferrin ratios distinguish endometriosis stage and severity. Iron overload and shifting iron-binding protein profiles reveal a localized dysregulation that may influence disease progression and potentially pathogenic microbiome selection.

This chapter reviews hyperaccumulator plants, especially in the Brassicaceae family, and their mechanisms of metal uptake. It highlights implications for human health, including how high-metal diets may shift the microbiome toward dysbiosis—an insight relevant to conditions like endometriosis where metallomic imbalances and microbial disruptions intersect.

Fungal pathogens rely on metal acquisition for virulence. This review reveals how host tissues manipulate iron, copper, zinc, and manganese to starve or intoxicate fungi and how pathogens adapt, with implications for antifungal therapy and microbiome-targeted interventions.

Nickel-dependent enzymes like urease and hydrogenase are essential for pathogen virulence. This review outlines the mechanisms by which pathogens acquire and utilize nickel and explores implications for therapy and microbiome balance.

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.

This review highlights how neurodegenerative diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB) exhibit disease-specific metallomic signatures, with copper depletion as a shared feature. Metal imbalances reflect both cause and consequence in neurodegeneration and may offer diagnostic potential when captured through region-specific elemental analysis.

Dementia with Lewy bodies (DLB) brains show widespread copper depletion and region-specific sodium, manganese, iron, and selenium alterations. While copper loss is common to AD and PDD, DLB presents a distinct metallomic fingerprint, enabling disease differentiation via PCA. Metallomic profiling may aid in diagnosing overlapping dementias and reveals unique pathophysiological signatures.

This study identifies a distinct urinary metallomic signature in pancreatic cancer patients, marked by altered calcium, magnesium, copper, and zinc levels, along with lighter zinc isotopic composition. These findings suggest that non-invasive urine tests could enable early PDAC detection by leveraging trace metal imbalances and stable isotope shifts.

A metallomic signature is the condition-specific profile of trace metals and metal-binding molecules that reflects disrupted metal homeostasis.

This literature review maps the microbiome signature of endometriosis across multiple body sites, revealing distinct taxa enriched or depleted in patients compared to controls, highlighting microbial shifts by disease stage, site, and taxa. 

Facultative anaerobes are microorganisms—primarily bacteria—that possess the metabolic flexibility to grow in both the presence and absence of oxygen.

Nickel plays a crucial role in Escherichia coli, serving as a cofactor for hydrogenases, urease, and detoxification enzymes. These functions support metabolism, acid resistance, and virulence in pathogenic strains like STEC. E. coli also employs specialized nickel acquisition systems to counteract host-imposed metal sequestration, ensuring enzymatic activity in hostile environments.

A metalloprotease, also termed a metalloproteinase, is an enzyme that catalyzes the hydrolysis of peptide bonds in proteins, relying on metal ions—most commonly zinc (Zn²⁺), but also calcium (Ca²⁺), manganese (Mn²⁺), or cobalt (Co²⁺)—as essential cofactors for its catalytic activity. Classified within the broader group of proteases (peptidases), metalloproteases are distinct due to their metal-ion […]

Nutritional immunity restricts metal access to pathogens, leveraging sequestration, transport, and toxicity to control infections and immunity.

This review definitively showcases lactoferrin’s antimicrobial prowess against resistant bacteria, detailing its mechanisms, effects on virulence factors like biofilms, and potential to restore microbial balance, marking it as a vital therapeutic ally for clinicians.

This study confirms elevated lactoferrin and anti-lactoferrin antibody levels in endometriosis, suggesting autoimmune involvement. Anti-lactoferrin drops post-surgery, hinting at a biomarker role, while lactoferrin ties to inflammation and potential microbiome links.

What was studied?This study investigated the causal relationship between gut microbiome composition and endometriosis using a two-sample Mendelian randomization (MR) approach. The researchers aimed to determine whether specific gut microbiota taxa have a direct causal effect on endometriosis risk rather than a mere observational association.Who was studied?The study utilized genome-wide association study (GWAS) summary statistics […]

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.

A patient with refractory celiac disease type II achieved complete duodenal villi recovery and symptom resolution after fecal microbiota transfer.

Microbial Metallomics is the study of how microorganisms acquire, use, regulate, and transform metals in any biological or environmental context.

The BBB is a crucial regulatory interface between the circulatory and central nervous systems, and its dysfunction has profound implications for neurodegeneration, inflammation, and systemic disease. Increasing evidence supports the role of the gut microbiome in BBB modulation, highlighting microbiome-targeted therapies as a promising avenue for maintaining neurological health and preventing age-associated cognitive decline.

This review explores the microbiota–gut–brain axis, highlighting the role of gut microbiota in barrier integrity and lymphatic transport. It discusses microbial metabolites, vagus nerve signaling, and meningeal lymphatics as critical communication pathways, emphasizing their implications for gastrointestinal and neurological disorders.

What Was Studied?This study examined the impact of heavy metal exposure on the prevalence and differentiation of osteoarthritis (OA) and rheumatoid arthritis (RA) using interpretable machine learning models. Researchers analyzed data from the National Health and Nutrition Examination Survey (NHANES) (2003–2020) to assess how various heavy metals contribute to arthritis risk.Who Was Studied?The study population […]

This study explored the association between rheumatoid arthritis and heavy metal exposure, identifying a significant deficiency of copper in RA patients. No significant correlations were found for zinc, cobalt, lead, or nickel. The findings suggest that copper deficiency may play a role in RA, warranting further research on trace metals in autoimmune diseases.

OverviewRheumatoid arthritis (RA) is a systemic autoimmune disease marked by chronic joint inflammation, synovitis, and bone erosion, driven by Treg/Th17 imbalance, excessive IL-17, TNF-α, and IL-1 production, and macrophage activation. Emerging evidence links microbial dysbiosis and heavy metal exposure to RA, [1][2] with gut microbiota influencing autoimmune activation via Toll-like receptor (TLR) signaling, inflammasome activation, […]

What was studied?This study investigated the taxonomic and functional gut microbiota profiles of euthyroid individuals with and without thyroid peroxidase antibodies (TPOAb), a marker for autoimmune thyroid diseases such as Hashimoto’s thyroiditis. The goal was to assess whether gut microbiota composition differs in individuals with TPOAb before the clinical onset of autoimmune thyroid disease and […]

This study identifies significant gut microbiota alterations in Hashimoto’s thyroiditis, with reduced beneficial microbes and increased pathogens.

This study revealed novel molecular signatures linking gut microbiota and transcriptome in Hashimoto’s thyroiditis, advancing diagnostic and therapeutic approaches.

Gut microbiota analysis in Hashimoto’s thyroiditis patients identified significant dysbiosis, with increased pro-inflammatory taxa and reduced beneficial microbes, correlating with thyroid autoantibodies.

This review explores the toxicity of heavy metals and pesticides in agricultural ecosystems, detailing their ecological and health impacts. It highlights pathways, bioaccumulation, and synergistic interactions, emphasizing the need for improved agricultural practices and bioremediation to mitigate these toxicants’ harmful effects on soil, plants, and human health.

The study reviewed adverse events linked to nickel hypersensitivity in Essure implants, noting rare reactions and the role of the menstrual cycle in modulating hypersensitivity.

Excess nickel disrupts gut microbiota, promoting dysbiosis and contributing to conditions like obesity and systemic nickel allergy syndrome (SNAS). Probiotics and nickel-restricted diets show promise in mitigating these effects, underscoring the need for further research and clinical intervention.

This review explores copper’s role in diabetes and diabetic kidney disease, emphasizing its impact on oxidative stress, glycemic control, and renal function. Findings highlight the potential of copper homeostasis as a therapeutic target and the Zn/Cu ratio as a biomarker for diabetes management and DKD progression.

This study evaluated the associations of zinc, copper, and Zn/Cu ratio with cardiometabolic risk factors in Qatari adults, revealing copper’s protective role and Zn/Cu ratio’s adverse implications for metabolic health.

Ammonium tetrathiomolybdate (TM) inhibits endometriosis progression in TNFR1-deficient mice by reducing copper and estradiol levels, lesion growth, angiogenesis, and oxidative stress.

This study links higher dietary zinc intake with increased endometriosis risk among American women, highlighting zinc’s complex role in immune modulation and estrogen-related pathways. Findings emphasize the importance of balanced intake for managing endometriosis risk.

Chronic chlorpyrifos exposure induces obesity and insulin resistance by altering gut microbiota, increasing gut permeability, and driving inflammation.

Nickel allergy, smoking, and dietary nickel intake may worsen chronic fatigue and muscle pain. Managing exposure can improve symptoms.

This review highlights how gluten-free, Mediterranean, and anti-inflammatory diets improve pain perception in endometriosis by reducing inflammation and modulating the gut microbiome. Probiotics and bioactive nutrients such as curcumin enhance therapeutic outcomes.

This review explores how dietary modifications impact endometriosis progression. Antioxidants, omega-3s, and anti-inflammatory diets show promise in symptom relief and hormonal regulation. Personalized nutrition emerges as a pivotal tool for improving patient outcomes.

This study examined blood nickel and endometriosis, revealing significantly higher nickel levels in affected Sri Lankan women, supporting a potential metalloestrogenic role.

This case report describes markedly elevated lead, nickel, and bismuth in the peritoneal fluid of a young woman with endometriosis, highlighting dietary and environmental exposure considerations and potential biomarker relevance.

The Bradford Hill Criteria emphasized a holistic assessment of evidence to determine causality rather than requiring rigid experimental proof.

OverviewMetal Homeostasis Copper dysregulation plays a definitive role in the pathogenesis of Type 1 Diabetes Mellitus (T1DM). Elevated copper levels increase the risk of developing T1DM by 15-fold per standard deviation, highlighting copper’s critical influence on oxidative stress and inflammatory pathways central to the disease. Studies show that T1DM patients exhibit higher copper levels and […]

Microbiome findings provide mechanistic insights into how chlorhexidine (CHX) mouthwash might contribute to breast cancer and breast disease in a causal manner.

The study linked reduced oral microbiome diversity and altered microbial profiles to breast cancer and non-malignant breast disease, highlighting strong correlations between oral and fecal microbiomes in cases versus controls. Genera such as Porphyromonas showed significant inverse associations with breast cancer risk.

Microbial dysbiosis, marked by reduced bacterial load and altered species composition, is linked to breast cancer progression. Enrichment of Methylobacterium radiotolerans in tumors and depletion of Sphingomonas yanoikuyae in normal tissue suggest diagnostic and therapeutic potential for microbiota-based interventions in breast cancer.

Gut microbiota influences early breast cancer prognosis and treatment side effects, with specific commensals correlating to outcomes. Chemotherapy alters microbiota, favoring beneficial species and improving immune modulation and neuroprotection.

This study reveals distinct gut microbiota profiles in breast cancer and DCIS patients, with reduced alpha diversity and functional shifts linked to inflammation. Major microbial associations, including enriched Bacteroides guilds, underscore potential microbiome-targeted interventions. Oral microbiota showed minimal differences, highlighting the gut’s critical role in breast cancer progression.

The study revealed altered gut microbiota in postmenopausal breast cancer patients, with enriched inflammation-associated species and depleted butyrate producers. Functional gene changes suggest links to systemic inflammation and metabolic imbalance, providing insights into microbiota’s role in cancer progression.

This study shows that breast cancer, rather than menopausal status, drives subtle gut microbiota changes. Dysbiosis in BC patients included reduced Blautia obeum and Bifidobacterium. Functional impacts, such as downregulated NAD pathways, suggest gut microbiota’s potential role in cancer progression.

BL21 improved metabolic, hormonal, inflammatory, and microbiome dysfunction in a DHT-induced PCOS model, restoring beneficial taxa and supporting gut–brain–ovary axis regulation.

A 4-week prebiotic diet in PD patients increased faecal SCFAs, improved gut-brain metabolite profiles, and alleviated gastrointestinal symptoms, but core dysbiosis persisted. Results support microbiota-directed dietary interventions as a promising adjunct for Parkinson’s management.

This study characterizes ASD gut microbiome signatures, identifies microbial and cytokine disruptions, and evaluates diet and probiotics as targeted modulators of microbial–immune networks in Colombian children.

A longitudinal study showing that specific bacterial vaginosis subtypes and microbial networks strongly predict Chlamydia trachomatis acquisition, reinfection, and sequelae in adolescents and young women.

Metaproteomic profiling revealed Candida-rich communities in BV-negative women, while Malassezia and Conidiobolus characterized BV-positive states. Functional shifts and strong fungal–bacterial associations highlight intertwined ecological dynamics.

Gut microbiome dysbiosis precedes kidney transplant rejection, marked by loss of SCFA-producing taxa, reduced diversity, and enrichment of disease-associated bacteria. This prerejection signature reflects a prolonged CKD-like state and may serve as an early biomarker and therapeutic target.

This study shows how a toxic gut microbiome enriched in uraemic toxin-producing species drives CKD progression, validated across cohorts and animal models, with diet emerging as a modifiable factor.

This study shows that diet strongly alters gut microbiota in CKD, with low-protein, high-fiber intake enhancing SCFA-producing bacteria and reducing TMAO and inflammation.

This study links reduced gut microbial diversity and specific taxa (e.g., Acidaminococcus, Hungatella) to breast cancer, influenced by diet. Findings suggest microbiome-targeted interventions and dietary strategies could mitigate breast cancer risk.

This study identifies gut dysbiosis in breast cancer patients, highlighting reduced SCFA-producing bacteria and altered microbial pathways. Findings suggest microbiome-targeted interventions could aid breast cancer treatment.

This study explores the mammary microbiota’s composition and function before and after breast cancer diagnosis, revealing dysbiosis and metabolic shifts as early markers.

The study analyzed breast tumor and adjacent tissues, linking microbiota composition to cancer pathways. Key findings implicate specific microbes in breast cancer progression.

What was studied?This study investigated the gut microbiota profiles, diagnostic value, and functional pathways specific to premenopausal breast cancer patients. It aimed to identify unique gut microbial markers distinguishing premenopausal breast cancer patients from postmenopausal patients and age-matched controls. The study also explored functional pathways of gut microbiota linked to breast cancer progression and diagnostic […]

This review highlights microbiome alterations in endometriosis, including gut and vaginal dysbiosis, and explores microbiome-targeted therapies and diagnostics.

Pueraria lobata extract enhances antioxidant activity and modulates gut microbiota by increasing Lactobacillaceae and Bacteroidetes while reducing harmful taxa.

This review assesses plant-derived agents for endometriosis therapy, focusing on mechanisms like inflammation, angiogenesis, and apoptosis. Key agents such as resveratrol and curcumin show preclinical promise, while Chinese herbal medicine (CHM) demonstrates clinical utility.

What Was StudiedThis study explored the potential link between the consumption of fruits and vegetables and the risk of laparoscopically confirmed endometriosis. Using data collected from the Nurses’ Health Study II, the researchers analyzed dietary habits over a 22-year period, investigating whether certain food groups and nutrients influenced the likelihood of developing endometriosis.Who Was StudiedParticipants […]

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.

HBOT demonstrates complete remission and holds significant promise as a candidate for microbiome-targeted intervention for endometriosis.

This study demonstrates hyperbaric oxygen therapy (HBOT) achieves complete remission of endometriotic lesions in a rat model by reducing hypoxia, inflammation, and TNF-α levels. While HBOT shows potential as a non-invasive therapy for endometriosis, further studies are needed to validate its impact on microbiome modulation.

This study highlights hyperbaric oxygen therapy’s (HBOT) role in reducing inflammation and NFκB expression in a mouse model of endometriosis. The findings suggest HBOT as a promising non-invasive treatment for managing endometriosis-associated inflammation, targeting hypoxia-induced molecular pathways and offering potential microbiome benefits through reduced inflammatory burden.

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.

This review highlights the potential of plant-derived therapies for endometriosis. Key findings include anti-inflammatory, anti-proliferative, and anti-angiogenic effects of herbal extracts and bioactive compounds, offering safer long-term alternatives to conventional treatments.

Metronidazole is a validated microbiome-targeted intervention (MBTI) for endometriosis, reducing key dysbiotic taxa and suppressing inflammation and lesion progression.

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.

Hyperglycemia weakens placental immunity in GDM, increasing bacterial invasiveness. Metformin reduces bacterial counts of E. coli and S. agalactiae, providing protective benefits beyond insulin. Cytokine tolerization under hyperglycemia highlights the need for enhanced therapeutic interventions.

Pueraria Flower Extract (PFE) addresses microbial imbalances and inflammation in endometriosis, validating its role as a microbiome-targeted therapy.

Pueraria thomsonii flower extract reduces visceral fat and BMI without sexual dimorphism, offering a safe intervention for obesity management.

This study demonstrates the potential of ¹H-NMR metabolomics to diagnose endometriosis non-invasively by identifying metabolic biomarkers and disrupted pathways. Quadratic Discriminant Analysis outperformed Artificial Neural Networks in diagnostic accuracy.

This study used 1H-NMR metabonomics to identify serum biomarkers for early endometriosis diagnosis. Elevated lactate, alanine, and reduced glucose levels highlight metabolic disruptions, offering a minimally invasive diagnostic tool.

This study highlights metabolic alterations in endometrial tissue and serum of minimal and mild endometriosis patients, identifying amino acid biomarkers with diagnostic potential. A combined serum panel demonstrated 100% sensitivity and 83% specificity for Stage II diagnosis, offering a promising step toward non-invasive early detection of endometriosis.

This study links cervical microbiome diversity with endometriosis severity. Findings reveal microbial imbalances, particularly in advanced stages, correlate with pain, infertility, and inflammatory pathways. The cervical microbiome may serve as a diagnostic and therapeutic target for improving outcomes in endometriosis, highlighting its role in reproductive health and disease progression.

This review highlights the bidirectional relationship between endometriosis and the microbiome, showcasing dysbiosis as a key factor in inflammation and estrogen metabolism. Emerging microbiome-targeted therapies hold promise for diagnosis and treatment.

This review highlights the gut and genital microbiome’s roles in estrogen-driven conditions like endometriosis, infertility, and CPP, emphasizing dysbiosis’ impact on inflammation and estrogen metabolism.

The study links lead and cadmium exposure to increased endometriosis risk, emphasizing lead’s role at low blood levels and synergistic effects with cadmium. It advocates for strict monitoring and preventive measures to minimize exposure.

This study quantified metalloestrogens—cadmium, nickel, and lead—in ectopic endometrial tissue, suggesting their role in endometriosis persistence.

This study identifies nickel allergy as an independent risk factor for endometriosis, highlighting shared immune dysregulation and estrogenic pathways. Using a population-based cohort, researchers found a 2.5-fold increased odds of nickel allergy in women with endometriosis, emphasizing the role of environmental exposures in its pathogenesis.

This review explores bacterial iron homeostasis, focusing on detoxification pathways, oxidative stress mitigation, and iron-storage mechanisms. It highlights regulatory proteins like Fur and DtxR and storage proteins like ferritins. These insights provide potential therapeutic targets for limiting bacterial growth and addressing iron-related dysbiosis in host-pathogen interactions.

This review explores the role of trace elements and oxidative stress in endometriosis, highlighting their potential as therapeutic targets. It underscores the need for further research into the trace elements’ roles in endometriotic lesions.

Iron overload in endometriosis contributes to oxidative stress, inflammation, and tissue damage, driving lesion persistence and subfertility. Ferroptosis resistance and dysregulated iron metabolism highlight therapeutic opportunities using iron chelators and modulators.