High Prevalence of Nickel Allergy in an Overweight Female Population: A Microbial Metallomics Commentary Original paper
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Women’s Health
Women’s Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
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Microbial Metallomics
Microbial Metallomics
Microbial Metallomics is the study of how microorganisms interact with metal ions in biological systems, particularly within the human microbiome.
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Low‑Nickel Diet (LNiD)
Low‑Nickel Diet (LNiD)
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
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, Low-Nickel Diet (LNiD) on BMI and waist circumference in nickel-sensitive individuals. The authors sought to evaluate whether nickel hypersensitivity is more common in overweight individuals and whether nickel restriction could offer metabolic benefits.
Who was studied?
The study involved 87 overweight adults (BMI > 26 kg/m²), predominantly female (72 of 87). Participants were screened for nickel allergy via standard patch testing. Among these, 43 women and 2 men tested positive and were advised to follow a low-nickel diet (80–100 µg/day). A 6-month follow-up was completed by 24 allergic overweight women, whose BMI, waist circumference, and body fat percentage were tracked as outcome variables.
Most Important Findings
The prevalence of nickel allergy in overweight women was 59.7%, substantially higher than the 12.5% seen in the general female population. In those with both metabolic syndrome and liver steatosis, the prevalence rose to 61.1%. A normocaloric, Low-Nickel Diet (LNiD) significantly reduced BMI (by 4.2 units), waist circumference (by 11.7 cm), and body fat percentage (by 5.1%) in the adherent cohort, all with p-values <0.001.
From a microbial perspective, the authors speculated that elevated dietary nickel may promote the growth or activity of nickel-dependent bacteria. This observation aligns with emerging concepts in microbial metallomics: many gut microbes use nickel as a catalytic cofactor in key enzymes such as urease, [NiFe]-hydrogenase, and glyoxalase I—enzymes directly linked to microbial virulence, stress response, and survival in host environments. Helicobacter pylori, for instance, hoards nickel to support its colonization of the gastric mucosa. The authors even referenced studies suggesting that a low-nickel diet enhances H. pylori eradication.
This pilot study opens the door to consider nickel-dependence as a defining functional trait in specific gut microbial populations associated with obesity. Excess nickel intake may act as a selective pressure that favors nickelophilic organisms, which in turn may modulate host immunity and metabolism. Moreover, nickel-selective dysbiosis may represent an unrecognized microbial signature in overweight individuals, particularly women with metabolic syndrome and liver steatosis.
IL-17, a cytokine elevated in both obesity and nickel hypersensitivity, provides a mechanistic bridge. Nickel-specific T cells produce IL-17, and menopausal estrogen deficiency further upregulates this cytokine. Taken together, a nickel-driven Th17 inflammatory axis may amplify gut inflammation and metabolic disruption through both host immune mechanisms and microbial activation pathways.
Greatest Implications
The data suggest that overweight women, especially those with comorbid metabolic dysfunction, may harbor nickel-selective microbial communities contributing to obesity through metallomic and immunologic pathways. Clinically, this highlights the need to screen for nickel allergy in metabolic and obesity management settings and suggests that nickel restriction may serve as a dual-purpose intervention, addressing both allergic and metabolic symptoms. From a microbiome signatures perspective, this study supports the inclusion of nickel-dependent microbial traits as part of a broader metallomic signature for obesity and metabolic syndrome. Interventions like a Low-Nickel Diet (LNiD) or nickel chelators (e.g., lactoferrin or dimethylglyoxime (DMG) may represent microbiome-targeted strategies that alter not only dietary exposure but microbial composition and activity. Further metagenomic and metallomic analyses are warranted to define nickel-dependent microbial associations and their causal contributions to the obese phenotype.
Low‑Nickel Diet (LNiD)
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Low‑Nickel Diet (LNiD)
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Urease
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.
Microbiome Signatures Definition: A Conceptual Advancement for Translational Microbiome Science
Microbiome signatures are reproducible ecological and functional patterns—encompassing traits, interactions, and metabolic functions—that reflect microbial adaptation to specific host or environmental states. Beyond taxonomy, they capture conserved features like metal metabolism or immune modulation, enabling systems-level diagnosis and intervention in health and disease.
Metallomic Signatures
A metallomic signature is the condition-specific profile of trace metals and metal-binding molecules that reflects disrupted metal homeostasis.
Low‑Nickel Diet (LNiD)
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
Lactoferrin
Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein classified as a postbiotic with immunomodulatory, antimicrobial, and prebiotic-like properties.