Karen Pendergrass, Standards Team

The Microbial Metallomics Theory of Parkinson’s Disease, as a unified disease-specific framework integrating ferroptosis, microbial dysbiosis, metallomic selection, and α-synuclein pathology, is credited to Karen Pendergrass.

This review unifies Parkinson’s disease mechanisms under a single framework of heavy metal-induced ferroptosis, microbial virulence, and α-synuclein aggregation, emphasizing the central role of metal-driven dysbiosis and gut-brain axis propagation.

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Lactulose is a non-absorbable disaccharide composed of galactose and fructose that functions as a prebiotic, a selectively fermented ingredient that promotes the growth of beneficial microorganisms in the gut.

Lactulose improved fecal microflora in CKD patients by significantly increasing Bifidobacteria and Lactobacilli while stabilizing renal function. These microbiome shifts counteract dysbiosis-associated toxin generation, supporting lactulose as a clinically relevant microbiome-targeted intervention.

Lactulose functions as a validated microbiome-targeted intervention for CKD by suppressing dominant pathogenic taxa such as Escherichia-Shigella while enriching depleted SCFA-producing bacteria like Bifidobacterium. This dual modulation reduces uremic toxin generation, restores intestinal function, and mechanistically slows CKD progression through targeted correction of dysbiosis.

Lactulose improved renal function in adenine-induced CKD rats by lowering uremic toxins, decreasing indole-producing taxa, and enriching Bifidobacterium and Lactobacillales. These microbiome shifts corresponded with reduced fibrosis and oxidative stress, demonstrating lactulose’s potential as a microbiome-targeted intervention for CKD.

In MSAP patients with gut dysfunction, lactulose and rhubarb similarly restored intestinal function, but lactulose more effectively reduced TNF-α and IL-6, enriched Bifidobacterium and Lactobacillales, suppressed Escherichia-Shigella and Enterococcus, and enhanced SCFA production, supporting its role as a microbiome-targeted intervention in acute pancreatitis.

Chelation is a biochemical and pharmacological process in which small-molecule chelating agents bind to metal ions with high affinity to sequester, redistribute, or remove metallic elements from biological systems.

Unlike antibodies that fight infections by targeting foreign pathogens, autoantibodies mistakenly target the body’s own cells and tissues, attacking what should be recognized as “self”. This loss of immune tolerance represents a fundamental breakdown in one of the immune system’s most important mechanisms: the ability to distinguish between self and non-self.

Microbiome medicine reframes humans as holobionts and uses microbial signatures, sequencing, and computational tools to guide diagnosis, prevention, and treatment. By targeting microbial functions rather than isolated taxa, it enables genuinely personalized interventions that are already beginning to move from association studies into clinical practice.

This study systematically compares 71 compounds for anti ureolytic activity, linking nickel chelation, transporter specific nickel uptake, and urease inhibition in Klebsiella pneumoniae and recombinant systems to inform rational selection of metallomic strategies against urease positive pathobionts in clinical and environmental settings.

Ni(II) Cd(II) mixed ligand complexes showed broad in vitro antimicrobial activity against key bacterial and fungal pathogens and moderate anti-inflammatory effects via albumin denaturation inhibition, supporting metal chelation as a tunable strategy for targeting dysbiosis associated pathobionts while highlighting significant toxicity related translational constraints.

This study shows that nickel strongly enhances Aβ40 aggregation, while the nickel chelator dimethylglyoxime inhibits amyloid beta aggregation by sequestering nickel in vitro. It also links nickel to both metal-driven and infection-related Alzheimer’s mechanisms, positioning nickel chelation at the intersection of these pathogenic pathways.

C. albicans protects P. gingivalis from immune detection by enhancing gingipain activity, suppressing cytokine signaling, and promoting chronic bacterial persistence. Mixed biofilms weaken macrophage and fibroblast responses and alter infection severity in vivo, demonstrating a cross-kingdom partnership that reshapes periodontal disease pathogenesis.

This review integrates ecological and immunological data on microbiome-based-interventions, linking specific taxa, diets, and microbial metabolites to gut community shifts, barrier function, and adaptive immunity, and outlining translational opportunities and risks for clinically targeted microbiome modulation.

Dysbiosis in chronic kidney disease (CKD) reflects a shift toward reduced beneficial taxa and increased pathogenic, uremic toxin-producing species, driven by a bidirectional interaction in which the uremic environment disrupts microbial composition and dysbiotic metabolites accelerate renal deterioration.

This review summarizes evidence linking physical activity to reduced breast cancer risk, with significant benefits for postmenopausal women. Mechanisms include hormonal modulation, reduced inflammation, enhanced immunity, and potential microbiome interactions, supporting exercise as a key preventive strategy.

Lactoferrin and its peptides exhibit broad antifungal activity through membrane disruption, immunomodulation, and iron sequestration, with documented synergy with azoles. Lactoferricin B is potent against dermatophytes, including Microsporum canis, and exemplifies how antimicrobial peptides can pair metallomic deprivation with rapid candidacidal effects.

Zinc oxide nanoparticles inhibited Microsporum canis growth in a concentration-dependent manner and significantly reduced SUB1 virulence-gene expression. MIC values of 250–500 ppm and fungicidal activity at 500–1000 ppm indicate strong antifungal potential with implications for nanoparticle-based veterinary antifungal strategies.

Short-chain fatty acids are microbially derived metabolites that regulate epithelial integrity, immune signaling, and microbial ecology. Their production patterns and mechanistic roles provide essential functional markers within microbiome signatures and support the interpretation of MBTIs, MMAs, and systems-level microbial shifts across clinical conditions.

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract that can cause a wide range of symptoms, including abdominal pain, diarrhea, and fatigue. The exact cause of the disease remains unclear, but it is believed to result from a combination of genetic predisposition and environmental factors. Although there is no cure, ongoing advancements in medical research continue to improve management strategies and quality of life for those affected by Crohn’s disease.

Iron supplementation in infants reduces Bifidobacterium abundance by 6.37%, as confirmed by meta-analysis. While critical for anemia prevention, oral iron may disrupt the infant gut microbiota, potentially supporting pathogen growth. Prebiotic co-administration could mitigate adverse effects.

High-dose enteral iron supplementation in VLBW infants was associated with reduced microbial diversity, Proteus enrichment, and increased microbial potential for ferroptosis and epithelial invasion, highlighting risks of intestinal dysbiosis.

This review outlines current strategies targeting siderophore biosynthesis as a therapeutic approach to microbial infections, emphasizing enzyme-specific inhibitors, nanoparticle delivery, and CRISPR-based interventions to impair iron acquisition and reduce virulence.

This review outlines how Staphylococcus aureus overcomes host nutritional immunity by acquiring iron, manganese, and zinc, underscoring the critical role of metal transport systems in virulence and immune evasion.

This review details recent enzymatic and structural insights into NRPS-dependent and NRPS-independent siderophore biosynthesis, emphasizing implications for antimicrobial development and microbiome-targeted therapies.

Siderophores are microbial iron-chelating molecules that enable pathogens to overcome host iron restriction, shape microbiome ecology, and serve as therapeutic targets.

Redundant siderophores and an Sst catechol transporter enable Staphylococcus aureus iron acquisition from transferrin, including catecholamine-liberated and xenosiderophore-bound pools, and jointly drive virulence in mice. Targeting Hts, Sir, and Sst impairs growth and organ colonization.

XusB in Bacteroides thetaiotaomicron binds enterobactin in OMVs, sustains commensal fitness, and creates a lipocalin 2 resistant iron pool that Salmonella can recapture, redefining commensal-iron-acquisition-and-nutritional-immunity during colitis.

Aferric enterobactin disables myeloperoxidase, granting E. coli a survival edge in colitis, while lipocalin 2 restores enzyme function and counters colonization.

Lipocalin 2 sequesters enterobactin to starve bacteria of iron, while the iroA cluster glucosylates enterobactin into salmochelins that evade capture, sustaining virulence. Targeting iroA may restore host iron withholding without disrupting commensals.

HrtA is the ATPase of HrtAB that protects S. aureus from heme toxicity. Catalytic residues are essential in vitro and in vivo. Heme-stressed hrtA mutants undergo stringent-like reprogramming with a shift from cytolytic to immunomodulatory toxins, redefining virulence control by heme availability.

This review integrates host nutritional immunity with UPEC transition metal control, detailing siderophore and metallophore functions, copper “nutritional passivation,” and interspecies antagonism, and outlines translational targets for diagnostics and therapy in urinary tract infection.

What was reviewed?This editorial synthesizes evidence on the role of iron in bacterial pathogenesis, emphasizing how iron scarcity and host nutritional immunity shape virulence, metabolic strategy, and antibiotic tolerance across diverse pathogens. Mechanisms covered include siderophore production and piracy, heme acquisition, ferrous iron uptake via Feo, and regulatory circuitry such as Fur and the newly […]

This review maps the battle for iron between bacterial pathogens and hosts, detailing nutritional immunity, bacterial siderophores and heme uptake, siderocalin defense, stealth siderophores, and clinical implications for infection risk, vaccines, and microbiome-informed care.

This review summarizes evidence that both low and high plasma iron increase infection risk, particularly in individuals with HFE C282Y homozygosity. Maintaining stable transferrin saturation is vital for immune function, with implications for managing hemochromatosis and iron deficiency to prevent infections and support microbiome health.

OverviewIron is a pivotal nutrient at the host–pathogen interface. Virtually all microbes (with rare exceptions like Borrelia) require iron for processes from DNA synthesis to respiration. [1] In human hosts, free iron is vanishingly scarce due to “nutritional immunity,” wherein iron is locked up in hemoproteins or tightly bound by transport proteins.[2] This metal tug-of-war […]

This review details how nutritional immunity shapes host–pathogen interactions through metal sequestration and intoxication, highlights key microbial metal acquisition systems, and discusses their implications for microbiome signatures and the development of novel antimicrobial therapies.

OverviewInductively Coupled Plasma Mass Spectrometry (ICP-MS) is an analytical technique used to determine the elemental composition of a sample by ionizing the sample with an inductively coupled plasma and then measuring the mass-to-charge ratio of the ions. ICP-MS is a highly sensitive method, capable of detecting elements at trace and ultra-trace levels, making it valuable in […]

Candida albicans enables systemic Staphylococcus aureus infection via Als3p-mediated hyphal invasion. This “microbial hitchhiking” allows S. aureus to bypass epithelial barriers, with major implications for immunocompromised patients.

This comparative study evaluated ketoconazole and hypochlorous acid for dermatophytosis in cats and dogs. Ketoconazole outperformed HOCl in microscopic clearance, though both showed strong clinical improvement. HOCl may serve as a partial alternative pending further optimization.

Cold atmospheric plasma significantly inhibited T. rubrum and M. canis growth in vitro, matching the efficacy of ciclopirox olamine. Daily 10-minute CAP treatments proved most effective, acting through ROS/RNS mechanisms, offering a promising contact-free alternative to systemic or topical antifungals.

Ciclopirox and its salt form exhibit broad-spectrum antifungal, antibacterial, and anti-inflammatory activity via iron chelation and enzyme inhibition. With low resistance potential, they outperform many azoles and show promise in oncology, virology, and neuroinflammation, making them valuable tools in dermatology and beyond.

A single case of M. canis dermatophytosis in a dog was cured using Methylene blue-mediated antimicrobial photodynamic therapy (MB-APDT), with no recurrence after 6 months. This suggests MB-APDT is a fast, effective, and safe treatment for dermatophytosis in companion animals.

Zinc ions enhanced siderophore production in fungi from Panax ginseng rhizosphere, with optimal levels at 150 µg/ml. Penicillium commune JJHO produced ferrichrome-type siderophores, suggesting zinc may drive microbial adaptations in metal-rich environments with implications for plant health and bioremediation.

This study found that berberine and palmatine hydrochloride synergistically inhibit M. canis by disrupting cell structure and modulating virulence-related genes. The combination outperformed clotrimazole in vivo, showing strong potential for treating dermatophytosis.

Fluconazole downregulates the metallothionein gene in Microsporum canis, enhancing copper cytotoxicity. This ergosterol-independent antifungal mechanism reveals a novel vulnerability in M. canis and identifies metallothionein as a promising therapeutic target.

HapX regulates iron metabolism in A. benhamiae by controlling siderophore production and repressing iron-dependent genes, yet is dispensable for keratin-based virulence, suggesting compensatory iron acquisition strategies.

This study characterized the siderophores produced by Microsporum and Trichophyton species, revealing that M. canis secretes ferrichrome and ferricrocin under iron-limited conditions, indicating siderophore pathways as exploitable therapeutic targets.

Genome sequencing of feline and canine Microsporum canis reveals close genetic identity to an invasive human strain and dissects secreted CAZymes that drive keratin degradation and potential zoonosis.

This review outlines therapeutic strategies and susceptibility profiles for Microsporum canis, highlighting the need for standardized testing and noting poor efficacy for fluconazole and griseofulvin. Terbinafine and itraconazole remain preferred options.

Zinc deficiency significantly impairs Microsporum canis growth and virulence. The ZafA gene regulates zinc uptake and pathogenesis, and its deletion disrupts zinc transporters, conidiation, and host infection, suggesting it as a novel antifungal drug target.

This study identified catalase and hemolysin as key virulence factors linked to antifungal resistance in Microsporum canis strains from symptomatic hosts. Voriconazole, terbinafine, and posaconazole were most effective.

This case study confirmed Microsporum canis infection in cats through PCR and identified high antifungal resistance, with only itraconazole proving effective. These findings highlight the growing need for antifungal susceptibility testing in zoonotic dermatophytosis.

This study identified compound 2d as a potent antifungal agent against dermatophytes, demonstrating efficacy via ergosterol pathway suppression, cell wall disruption, and oxidative stress induction. It was non-toxic to mammalian cells, making it a strong candidate for further antifungal drug development.

This review outlines the pathogenic strategies of dermatophytes and host antifungal responses, with a focus on keratinolytic enzymes, PRRs, Th17 immunity, and CARD9-related immune dysfunction, offering insight into novel diagnostic and therapeutic strategies.

This review evaluates antifungal susceptibility and therapeutic options for Microsporum canis, highlighting methodological variability in testing and identifying terbinafine and itraconazole as the most reliable agents.

Ag₀.₉₉Fe₁.₀₁O₃ nanoparticles, especially when combined with cinnamon, clove, or lemongrass essential oils, exhibited strong synergistic antifungal effects against multiple dermatophytes, offering a promising strategy against antifungal resistance.

This US-based study reveals that M. canis genotype correlates with disease severity in cats, identifies three genetic clusters, and confirms the dominance of the MAT1-1 mating type. Conserved virulence genes (SSU1, SUB3) offer potential diagnostic utility.

This review details the enzymatic and genetic virulence arsenal of Microsporum canis, highlighting understudied factors like biofilms and dipeptidylpeptidases. Greater insight into these mechanisms could improve treatment and prevention strategies.

This study identified a metalloprotease gene family in Microsporum canis and confirmed in vivo expression of MEP2 and MEP3 during infection. MEP3, a keratinolytic enzyme, was expressed recombinantly and may contribute to fungal virulence, supporting its use in vaccine development.

Bee venom showed partial antifungal activity against resistant M. canis isolates, supporting its evaluation as a potential topical therapeutic. While not as potent as terbinafine, BV outperformed fluconazole and amphotericin B in susceptible isolates, highlighting its promise amid rising antifungal resistance.

OverviewMicrosporum canis (M. canis) is a zoophilic dermatophyte common in cats and dogs, responsible for 90% of feline dermatophytoses worldwide.[1][2] It has significant zoonotic potential, transmitting to humans through fomites or direct animal contact, causing severe superficial mycosis. M. canis is considered anthropo-zoophilic and can infect pediatric or immunocompromised patients, causing severe inflammatory responses such […]

A multi‑ethnic review summarising >80 genetic loci underlying Graves’ disease, their clinical correlates and emerging precision‑medicine applications.

This review maps the immune‑microbial mechanisms driving Graves’ disease and evaluates next‑generation biologics, small molecules and tolerance‑inducing peptides that may replace conventional ablation therapies.

This review links genetics, hormones, environment and especially viral exposures—EBV and HCV—to the Th1‑centric immunopathology of Graves’ disease, highlighting chemokine signatures relevant to microbiome‑based risk models.

Mendelian‑randomization of 18,340 MiBioGen participants and > 349k FinnGen controls identifies 32 gut genera with causal roles—some protective, others harmful—across six thyroid diseases, highlighting therapeutic microbiome targets.

Mendelian‑randomization of Japanese GWAS data shows a bidirectional genetic link between Graves’ disease and rheumatoid arthritis. The findings reinforce shared autoimmune pathways, highlight overlapping Prevotella‑dominant gut dysbiosis, and support reciprocal clinical screening and microbiome‑targeted interventions.

Graves Disease potentiates depression via autoimmune cytokines, hormonal excess and gut‑microbiome shifts. This review consolidates epidemiology and mechanisms, highlighting microbial signatures (Prevotellaceae, SCFA depletion) of translational interest.

Mendelian-randomization of East-Asian GWAS data shows Crohn disease genetics raise Graves disease risk, while ulcerative colitis genetics are protective, highlighting microbiome-immune pathways linking gut and thyroid autoimmunity.

This bidirectional Mendelian Randomization (MR) study establishes a causal link between Graves’ disease and gut microbiome alterations, confirming thyroid–gut axis interactions and identifying key microbial taxa as risk or protective factors.

This review maps the bidirectional interactions between toxic and essential metals and the gut microbiota, detailing microbial shifts and host impacts. It highlights specific microbial taxa disrupted by metals like arsenic, cadmium, and nickel, providing insight into metal-driven dysbiosis and its implications for disease pathogenesis.

This study shows that Staphylococcus aureus uses MntABC and MntH transporters to overcome host-imposed manganese starvation via calprotectin, preserving SOD activity and enabling systemic infection.

This review highlights Staphylococcus aureus as a multifaceted pathogen with niche-specific colonization, immune evasion, iron acquisition strategies, and extensive resistance mechanisms, emphasizing its microbiome interactions and emerging therapeutic targets.

This review examines bacterial resistance systems to toxic metals, detailing efflux pumps, ATPases, and metallothioneins. It explores their mechanisms, gene regulation, and clinical or environmental relevance.

This review outlines how S. aureus leverages diverse virulence factors—α-toxin, leukocidins, biofilms, and immune evasion mechanisms—regulated by systems like Agr to persist and cause disease. It discusses anti-virulence strategies and implications for targeted therapies.

Metallophores in S. aureus enable metal acquisition and virulence; disrupting these systems may offer novel antimicrobial strategies.

Urease enables S. aureus to survive acid stress and persist in murine kidneys. Its expression is regulated by CcpA and Agr, and its activity is essential for long-term infection, highlighting a critical microbial adaptation for persistence in acidic microenvironments.

Disabling NADH-dependent respiration in Staphylococcus aureus impairs biofilm and alpha-toxin production via fatty acid-mediated repression of the SaeRS system, significantly reducing virulence. These findings highlight metabolic pathways as promising antimicrobial targets.

This study sequenced and analyzed plasmids from poultry-associated Staphylococcus aureus, uncovering diverse resistance and virulence genes, novel mobilizable plasmids, and highlighting poultry as a reservoir for clinically relevant resistance determinants transferable to human strains.

The study demonstrates that Staphylococcus aureus adapts its glucose and lactate metabolism to oxygen levels, efficiently catabolizing lactate to acetate under aerobic conditions. This oxygen-dependent metabolic flexibility may provide a competitive advantage in human host niches.

This review systematically evaluates how trace elements influence thyroid hormone synthesis, metabolism, and disease pathogenesis, emphasizing their diagnostic, preventive, and therapeutic significance in clinical endocrinology.

This review summarizes current evidence on how trace elements influence thyroid hormone synthesis, metabolism, and the development of thyroid diseases, highlighting mechanistic links, clinical implications, and the interplay with the microbiome.

The study demonstrated that serum calprotectin is significantly elevated during acute subacute thyroiditis and drops with recovery, offering a novel, independent marker for disease activity, though it does not predict permanent hypothyroidism.

Lugdunin suppresses S. aureus colonization through direct antimicrobial action and by amplifying skin innate immunity. It synergizes with host antimicrobial peptides, promotes neutrophil recruitment via TLR/MyD88 pathways, and may serve as a novel adjunct or standalone topical treatment for MRSA skin infections.

Lugdunin is a microbiome-derived cyclic peptide antibiotic with direct anti-S. aureus activity and host immune-boosting effects. It induces LL-37 and CXCL8, recruits immune cells, and synergizes with host peptides, making it a promising candidate for MRSA and atopic dermatitis interventions.

Metallophores in S. aureus are critical for pathogenicity, enabling metal acquisition under nutritional immunity. This review highlights their biosynthesis, regulation, and role in virulence, identifying them as key microbial targets for diagnostics and therapy.

Pathobionts are native microbes with the capacity to cause disease under disrupted host or microbiome conditions.

This study shows that oxygen drives a shift in S. aureus metabolism from glucose fermentation to aerobic lactate oxidation. Lactate supports growth and energy production under oxygenated conditions, offering a survival advantage in host niches where sugars are scarce but lactate is abundant.

This review synthesizes key mechanisms of Staphylococcus aureus virulence, including colonization strategies, immune evasion, metabolic adaptability, and antimicrobial resistance. It highlights major microbial associations, such as siderophore-mediated modulation of the nasal microbiome and PVL-driven pathogenesis, offering translational insights for microbiome-targeted diagnostics, decolonization, and anti-virulence therapies.

This review outlines the role of metabolic endotoxemia—gut-derived LPS in circulation—in chronic inflammation and disease. It explores microbial, dietary, and immunological mechanisms underlying endotoxemia and evaluates antimicrobial peptides and microbiome-targeted diets as promising interventions.

In healthy adults, co-ingesting orange juice with a high-fat, high-carbohydrate meal dramatically blunted postprandial inflammatory responses. Orange juice prevented meal-induced rises in plasma endotoxin (LPS) and monocyte Toll-like receptor expression, highlighting a novel dietary strategy to counteract metabolic endotoxemia and oxidative stress, with implications for mitigating insulin resistance and atherosclerosis.

This review uncovers the dual role of urease as both a catalytic and multifunctional virulence protein with broad clinical and agricultural implications, highlighting its impact on microbiome composition, host-pathogen dynamics, and therapeutic strategy.

This study links nickel allergy to overweight status in women and shows that a low-nickel diet reduces BMI and waist size while suggesting immunologic and microbiome-related mechanisms.

Urease is a nickel-dependent microbial enzyme that breaks down urea into ammonia, altering local pH and nitrogen availability. While essential for microbial survival in acidic niches and nutrient-limited environments, urease activity also contributes to conditions like ulcers, urinary stones, colitis, and hepatic encephalopathy.

This review illustrates zinc’s dose- and species-dependent impact on gut microbiota, linking both deficiency and excess to dysbiosis and systemic inflammation. Physiological Zn enhances barrier integrity and probiotic efficiency, while excess Zn favors pathogens. Zn–microbiota interactions extend beyond the gut, influencing neurodevelopmental and metabolic diseases.

Excessive zinc intake may worsen endometriosis by activating estrogen receptors, disrupting immune function, and altering the microbiome. A large NHANES study found that intake above 14 mg/day significantly increases endometriosis risk. With many supplements exceeding this threshold, routine zinc supplementation may contribute to disease progression rather than prevention, prompting a Suggested Termination of Practice (STOP).

This study found no significant correlation between serum calprotectin levels and the severity of endometriosis. Despite its known role as an inflammatory biomarker, calprotectin did not differentiate between stages of disease, suggesting limited utility in clinical staging and reinforcing the need for localized biomarker assessment.

Hypersensitivity to mercury and nickel was significantly more common in fatigued and autoimmune patients than in healthy controls. Removal of dental metals reversed symptoms and immune activation, suggesting that metal-driven immune dysregulation may underlie fatigue and autoimmunity.