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References 2024-04-04 10:11:08
Metal Homeostasis majorpublished
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Metal Homeostasis
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Karen Pendergrass
Karen Pendergrass
Read MoreKaren 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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Kimberly Eyer
Kimberly Eyer
Read MoreKimberly Eyer, a Registered Nurse with 30 years of nursing experience across diverse settings, including Home Health, ICU, Operating Room Nursing, and Research. Her roles have encompassed Operating Room Nurse, RN First Assistant, and Acting Director of a Same Day Surgery Center. Her specialty areas include Adult Cardiac Surgery, Congenital Cardiac Surgery, Vascular Surgery, and Neurosurgery.
Transition metals like iron, zinc, copper, and manganese are crucial for the enzymatic machinery of organisms, but their imbalance can foster pathogenic environments within the gastrointestinal tract.
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Karen Pendergrass
Read More
Researched by:
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Karen Pendergrass
Karen Pendergrass
Read More
Fact-checked by:
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Kimberly Eyer
Kimberly Eyer
Read More
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
Overview
Metallomic homeostasis, or metal homeostasis, refers to the physiological and biochemical maintenance of balanced metal ion concentrations and metal-containing proteins within biological systems. This concept is central to understanding how organisms regulate the uptake, storage, distribution, and excretion of essential and toxic metal elements to maintain optimal cellular and physiological function. [1][2] The term encompasses the dynamic regulation of metal ions such as iron, copper, zinc, nickel, calcium, and manganese, which are critical cofactors in enzymatic reactions and structural components of numerous proteins. [3]
Essential Role
Metal ions are fundamental to virtually all aspects of cellular physiology. They serve as essential cofactors for enzymatic reactions and contribute to critical physiological processes including cellular energy production, signal transduction, structural integrity, and immune function.[4] The concept of metallome, the complete set of inorganic elements required for life, represents an often-overlooked dimension of cellular and organismal biology, comparable in importance to the proteome, metabolome, and lipidome.[5] Metals play structural, catalytic, and electron-transferring roles within cells, making their proper homeostasis indispensable for survival.[6]
Mechanisms of Metal Homeostasis
Organisms maintain metal homeostasis through a complex network of regulatory systems. These include diverse families of metal transporters, metallothioneins, and metal-responsive transcriptional regulators that work coordinately to regulate metal uptake, intracellular distribution, and excretion.[7] For example, zinc homeostasis is maintained through a sophisticated system involving multiple zinc transporters, zinc-binding proteins, and sensors of free zinc ions, collectively ensuring that zinc concentrations remain within physiological ranges despite fluctuating dietary intake. Similarly, iron homeostasis is regulated through the interaction of the peptide hormone hepcidin with the cellular iron exporter ferroportin, nutritional immunity factors that control iron absorption, recycling, and storage to maintain stable iron concentrations.[9]
Consequences of Dysregulation
Disturbed metal homeostasis, or metal dyshomeostasis, has profound consequences for human health and is implicated in the pathogenesis of numerous diseases. Brain metal homeostasis is particularly critical. Alterations in the homeostasis of metals such as copper, iron, and zinc are speculated to be involved in the etiology of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.[10][11] Metal dyshomeostasis has been associated with various cancer types, where elevated levels of certain metals like copper appear to be significant risk factors.[12] Additionally, disrupted metal homeostasis plays a role in metabolic disorders, including obesity and insulin resistance in children, where alterations in chromium, cobalt, and other metal-containing protein levels correlate with metabolic complications.[13]
Frequently Asked Questions
What is Metal Homeostasis?
Quick answer: Metallomic homeostasis, or metal homeostasis, refers to the physiological and biochemical maintenance of balanced metal ion concentrations and metal-containing proteins within biological systems. This concept is central to understanding how organisms regulate the uptake, storage, distribution, and excretion of essential and toxic metal elements to maintain optimal cellular and physiological function. [1][2] The term encompasses the dynamic regulation of metal ions such as iron, copper, zinc, nickel, calcium, and manganese, which are critical cofactors in enzymatic reactions and structural components of numerous proteins. [3]
Research Feed
Metallomic signatures of brain tissues distinguishes between cases of dementia with Lewy bodies, Alzheimer’s disease, and Parkinson’s disease dementia
June 26, 2024
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Parkinson’s Disease •
Parkinson’s Disease
Parkinson’s disease is increasingly recognized as a systemic disorder involving coordinated disturbances across the gut–brain axis, rather than a condition confined to dopaminergic neurodegeneration alone. Converging evidence implicates gut dysbiosis, altered microbial metabolites, impaired intestinal barrier integrity, and metal dyshomeostasis as upstream drivers of neuroinflammation and alpha-synuclein pathology. These interconnected microbiome, metabolomic, and metallomic signals provide a mechanistic framework for understanding disease initiation, progression, and therapeutic targeting beyond the central nervous system.
Metallomic Signatures •
Metallomic Signatures
Did you know?
Metallomic signatures can reveal hidden drivers of disease by mapping how trace metals like nickel, iron, and cadmium shape microbial behavior and immune responses. These signatures not only help identify toxic exposures but also spotlight metal-dependent pathogens, offering new targets for precision-guided therapies.
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Copper in microbial pathogenesis: meddling with the metal
February 16, 2012
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Microbes •
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains the key types of microorganisms, bacteria, viruses, fungi, protozoa, and archaea, along with major examples of pathogenic and beneficial species.
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Influence of heavy metal exposure on gut microbiota: Recent advances
August 13, 2023
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Women’s Health •
Women’s Health
Women’s health includes conditions like hormonal disorders, infertility, menopause, and reproductive cancers. Emerging research shows the microbiome plays a key role in disease development and treatment. MicrobiomeSignatures.com investigates condition-specific microbiome signatures to uncover disease causes and develop targeted microbiome-based therapies.
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Urinary lead concentration and composition of the adult gut microbiota in a cross-sectional population-based sample
September 10, 2019
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Microbes •
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains the key types of microorganisms, bacteria, viruses, fungi, protozoa, and archaea, along with major examples of pathogenic and beneficial species.
Alias iure reprehenderit aut accusantium. Molestiae dolore suscipit. Necessitatibus eum quaerat. Repudiandae suscipit quo necessitatibus. Voluptatibus ullam nulla temporibus nobis. Atque eaque sed totam est assumenda. Porro modi soluta consequuntur veritatis excepturi minus delectus reprehenderit est. Eveniet labore ut quas minima aliquid quibusdam. Vitae possimus fuga praesentium eveniet debitis exercitationem deleniti.
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Update History
Copper (Cu)
Copper serves as both a vital nutrient and a potential toxin, with its regulation having profound effects on microbial pathogenesis and immune responses. In the body, copper interacts with pathogens, either supporting essential enzyme functions or hindering microbial growth through its toxicity. The gastrointestinal tract, immune cells, and bloodstream are key sites where copper plays a crucial role in controlling infection and maintaining microbial balance. Understanding copper’s interactions with the microbiome and host defenses allows for targeted clinical strategies.
Zinc
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.
Nutritional Immunity
Nutritional immunity restricts metal access to pathogens, leveraging sequestration, transport, and toxicity to control infections and immunity.
Parkinson’s Disease
Parkinson’s disease is increasingly recognized as a systemic disorder involving coordinated disturbances across the gut–brain axis, rather than a condition confined to dopaminergic neurodegeneration alone. Converging evidence implicates gut dysbiosis, altered microbial metabolites, impaired intestinal barrier integrity, and metal dyshomeostasis as upstream drivers of neuroinflammation and alpha-synuclein pathology. These interconnected microbiome, metabolomic, and metallomic signals provide a mechanistic framework for understanding disease initiation, progression, and therapeutic targeting beyond the central nervous system.
Parkinson’s Disease
Parkinson’s disease is increasingly recognized as a systemic disorder involving coordinated disturbances across the gut–brain axis, rather than a condition confined to dopaminergic neurodegeneration alone. Converging evidence implicates gut dysbiosis, altered microbial metabolites, impaired intestinal barrier integrity, and metal dyshomeostasis as upstream drivers of neuroinflammation and alpha-synuclein pathology. These interconnected microbiome, metabolomic, and metallomic signals provide a mechanistic framework for understanding disease initiation, progression, and therapeutic targeting beyond the central nervous system.
Metallomic Signatures
A metallomic signature is the condition-specific profile of trace metals and metal-binding molecules that reflects disrupted metal homeostasis.
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains key microbe types, bacteria, viruses, fungi, protozoa, and archaea, plus major pathogenic and beneficial examples.
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.
Microbes
Microbes are microscopic organisms living in and on the human body, shaping health through digestion, vitamin production, and immune protection. When microbial balance is disrupted, disease can occur. This guide explains key microbe types, bacteria, viruses, fungi, protozoa, and archaea, plus major pathogenic and beneficial examples.
References
- The molecular landscape of cellular metal ion biology.. Aulakh.. (Cell Systems. 2025.)
- Correlative analysis of metallomic gene expression and metal ion content within the mouse hippocampus.. Mamsa.. (Metallomics. 2025.)
- Recent advances in the application of metallomics in diagnosis and prognosis of human cancer.. Zhang.. (Metallomics. 2022.)
- Lighting Up and Identifying Metal-Binding Proteins in Cells.. A. Tiemuer, H. Zhao, J. Chen, H. Li, and H. Sun.. (JACS Au, Nov. 2024.)
- The mouse metallomic landscape of aging and metabolism.. Morel.. (Nature Communications. 2022.)
- The impact of species, respiration type, growth phase and genetic inventory on absolute metal content of intact bacterial cells.. Budhraja.. (Metallomics. 2019.)
- The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis.. Shumin Sun, Enjun Xie et al.. (Advanced Science. 2024.)
- Zinc in Cellular Regulation: The Nature and Significance of “Zinc Signals”.. Wolfgang Maret.. (International Journal of Molecular Sciences. 2017.)
- Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis.. E. Nemeth, T. Ganz. (International Journal of Molecular Sciences. 2021.)
- Characterising the spatial and temporal brain metal profile in a mouse model of tauopathy.. Shalini S Rao, L. Lago et al.. (Metallomics. 2019.)
- Metallomic analysis of brain tissues distinguishes between cases of dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease dementia.. Scholefield M, Church SJ, Xu J, Cooper GJS.. (Front Neurosci. 2024 Jun 26;18:1412356.)
- Recent advances in the application of metallomics in diagnosis and prognosis of human cancer.. Yan Zhang, Jie He et al.. (Metallomics. 2022.)
- Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity.. lvaro Gonzlez-Domnguez, Mara Milln-Martnez et al.. (Nutrients. 2023.)
Mamsa.
Correlative analysis of metallomic gene expression and metal ion content within the mouse hippocampus.Metallomics. 2025.
Zhang.
Recent advances in the application of metallomics in diagnosis and prognosis of human cancer.Metallomics. 2022.
A. Tiemuer, H. Zhao, J. Chen, H. Li, and H. Sun.
Lighting Up and Identifying Metal-Binding Proteins in Cells.JACS Au, Nov. 2024.
Shumin Sun, Enjun Xie et al.
The Intestinal Transporter SLC30A1 Plays a Critical Role in Regulating Systemic Zinc Homeostasis.Advanced Science. 2024.
Wolfgang Maret.
Zinc in Cellular Regulation: The Nature and Significance of “Zinc Signals”.International Journal of Molecular Sciences. 2017.
E. Nemeth, T. Ganz
Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis.International Journal of Molecular Sciences. 2021.
Shalini S Rao, L. Lago et al.
Characterising the spatial and temporal brain metal profile in a mouse model of tauopathy.Metallomics. 2019.
Scholefield M, Church SJ, Xu J, Cooper GJS.
Metallomic analysis of brain tissues distinguishes between cases of dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease dementia.Front Neurosci. 2024 Jun 26;18:1412356.
Read ReviewYan Zhang, Jie He et al.
Recent advances in the application of metallomics in diagnosis and prognosis of human cancer.Metallomics. 2022.
lvaro Gonzlez-Domnguez, Mara Milln-Martnez et al.
Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity.Nutrients. 2023.