Karen Pendergrass, Standards Team

Update All Major Updates2025-11-03 13:04:59 Crohn’s Disease majorpublished1

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 LBW 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 RISPR-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 RPS-dependent and RPS-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.

B in Bacteroides thetaiotaomicron binds enterobactin in MVs, 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.

A is the TPase of AB 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 PEC 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 FE Y 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.

Iron is a pivotal nutrient at the host–pathogen interface. Virtually all microbes (with rare exceptions like Borrelia) require iron for processes from NA 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.

Inductively Coupled Plasma Mass Spectrometry (CP-S) 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. CP-S 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 OCl in microscopic clearance, though both showed strong clinical improvement. OCl 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 AP treatments proved most effective, acting through OS/NS 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 (B-PDT), with no recurrence after 6 months. This suggests B-PDT 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 JHO 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.

X 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 AZymes 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 A 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 CR 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, RRs, Th17 immunity, and ARD9-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.

O₃ 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 S-based study reveals that M. canis genotype correlates with disease severity in cats, identifies three genetic clusters, and confirms the dominance of the AT1-1 mating type. Conserved virulence genes (SU1, UB3) 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 EP2 and EP3 during infection. EP3, 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, V outperformed fluconazole and amphotericin B in susceptible isolates, highlighting its promise amid rising antifungal resistance.

Microsporum 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—BV and CV—to the Th1‑centric immunopathology of Graves’ disease, highlighting chemokine signatures relevant to microbiome‑based risk models.

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

Mendelian‑randomization of Japanese WAS 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, CFA depletion) of translational interest.

Mendelian-randomization of Asian WAS 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 (R) 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 ABC and H transporters to overcome host-imposed manganese starvation via calprotectin, preserving OD 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, TPases, 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 A and Agr, and its activity is essential for long-term infection, highlighting a critical microbial adaptation for persistence in acidic microenvironments.

Disabling ADH-dependent respiration in Staphylococcus aureus impairs biofilm and alpha-toxin production via fatty acid-mediated repression of the RS 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 LR/D88 pathways, and may serve as a novel adjunct or standalone topical treatment for RSA skin infections.

Lugdunin is a microbiome-derived cyclic peptide antibiotic with direct anti-S. aureus activity and host immune-boosting effects. It induces L-37 and XCL8, recruits immune cells, and synergizes with host peptides, making it a promising candidate for RSA 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 VL-driven pathogenesis, offering translational insights for microbiome-targeted diagnostics, decolonization, and anti-virulence therapies.

This review outlines the role of metabolic endotoxemia—gut-derived PS 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 (PS) 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.

What was studied?This pilot observational study assessed two interconnected phenomena: (1) the prevalence of nickel allergy in an overweight Italian population and (2) the impact of a normocaloric, Nickel Diet (NiD) on MI and waist circumference in nickel-sensitive individuals. The authors sought to evaluate whether nickel hypersensitivity is more common in overweight individuals and whether […]

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 HANES 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 (TOP).

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.

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

Nickel allergic contact mucositis was identified in over 90% of endometriosis patients with BS-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 (BS) and investigated the clinical efficacy of a low-nickel diet (NiD) 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 MAs in wound microbiomes, underscoring phages as viable interventions for biofilm-associated, drug-resistant infections.

Tinidazole shows strong alignment with endometriosis microbiome signatures by targeting MAs 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.

The Research Track (FT) 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 (D), Parkinson’s disease (D), and dementia with Lewy bodies (LB) 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 (LB) brains show widespread copper depletion and region-specific sodium, manganese, iron, and selenium alterations. While copper loss is common to D and DD, LB presents a distinct metallomic fingerprint, enabling disease differentiation via CA. 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 DAC 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 TEC. 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.