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Mismetallation majorpublished
Metals such as iron, zinc, copper, and manganese are essential for various biological processes, yet when they bind to the wrong proteins or enzymes, it can cause a cascade of negative effects, including oxidative stress, protein misfolding, and metabolic dysfunction. To counteract this, cells have evolved several defense mechanisms such as metallochaperones, metal transporters, and antioxidant systems, which ensure proper metal ion incorporation and protect against the detrimental consequences of mismetallation.
Mismetallation
Researched by:
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Divine Aleru
ID
Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
The human microbiome plays a critical role in metal metabolism, influencing both metal absorption and the potential for mismetallation in the body. Studies show that heavy metals can disrupt microbial diversity, leading to dysbiosis and altered metabolic functions in the gut. Moreover, some microbes possess the ability to sequester toxic metals, preventing their absorption and thus minimizing the risks of mismetallation in host tissues. As research in this area progresses, understanding these microbiota-metal interactions will be crucial for exploring new avenues in the prevention and treatment of metal-associated diseases.
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
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.
Divine Aleru
Metal ions such as iron (Fe), zinc (Zn), copper (Cu), manganese (Mn), and others are essential for life. They serve as cofactors in hundreds of enzymes that catalyze critical reactions including DNA synthesis, respiration, antioxidant defence, and metabolism.[1] When proteins bind the correct metal, this process is termed metallation, and it is often tightly regulated. However, when proteins mistakenly bind the wrong metal, the process is known as mismetallation.[2] Mismetallation can render enzymes inactive, impair cellular processes, induce oxidative stress, and contribute to disease states.
Mismetallation is the inappropriate incorporation of a metal ion into a metalloprotein or enzyme site that is designed for a specific metal. Many metalloenzymes have binding environments highly optimized for a particular metal’s chemistry, size, and coordination preferences. However, because metal availability and cellular conditions fluctuate, incorrect metals can sometimes occupy these sites and fail to support or actively hinder function. Mismetallation stems from two broad biochemical realities: Chemical Competitiveness, where some metal ions have similar ionic radii or ligand affinities (e.g., Zn²⁺ vs Mn²⁺), so in certain conditions a non‑cognate ion can outcompete the correct one.[3] Metal Availability Imbalance, where cells normally maintain metal homeostasis through transporters, chaperones, and storage proteins. But stress, metal toxicity, deficiency, or environmental exposure can alter these pools, raising mismetallation risk.[4]
Essential Metals and the Metallome
Roughly 30–40% of enzymes require metals for function, and vast numbers of proteins contain metal‑binding domains.[5] For example, nearly half of all human proteins may bind metal ions, including Zn in transcription factors or Fe in hemoglobin.
| Metal | Role | Common Metalloproteins |
|---|---|---|
| Iron (Fe) | Electron transfer, oxygen transport | Hemoglobin, cytochromes |
| Zinc (Zn) | Structural and catalytic roles | DNA polymerases, zinc-finger proteins |
| Copper (Cu) | Redox reactions | Cytochrome c oxidase, superoxide dismutase |
| Manganese (Mn) | Antioxidant enzyme cofactor | Mn‑superoxide dismutase |
| Magnesium (Mg) | DNA/RNA stabilization | DNA polymerase, ATP‑dependent enzymes |
Causes of Mismetallation
Oxidative Stress and Metal Displacement
Reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, can oxidize metal cofactors in enzymes like iron‑dependent mononuclear proteins. Oxidation destabilizes metal binding, causing the correct metal (e.g., Fe²⁺) to dissociate. In some cases, a less suitable metal (e.g., Zn²⁺) occupies the site, leading to an inactive enzyme.[6] This type of mismetallation is well documented in bacteria like Escherichia coli, which compensate by increasing manganese uptake to replace iron in critical enzymes.[7]
Imbalanced Metal Homeostasis
Cells depend on metallochaperones and transport proteins to safely direct metals to their right places.[8] Genetic defects or dietary metal extremes can overwhelm these systems, resulting in mismetallation. For example, when iron homeostasis is dysregulated, alternative metals like cadmium (Cd²⁺) can enter transport pathways intended for iron, competing with the correct metal and binding inappropriately.[9]
Environmental Metal Exposure
Chronic exposure to heavy metals such as lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) can create metal pools that perturb normal metal utilization and promote mismetallation. These metals can displace essential ions or induce oxidative stress that destabilizes normal metal centers.[10][11]
Nutritional Deficiencies
Deficiencies in essential metals reduce the availability of the correct metal, increasing the relative abundance of other available ions that can misincorporate into proteins.[12] For example, copper deficiency can lead to impaired metalloenzyme maturation and mismetallation in copper‑dependent proteins like superoxide dismutase.[13]
Pathogen and Immune Interactions
During infection, the host immune system restricts access to essential metals in a process called nutritional immunity, effectively depriving pathogens of critical resources, which can trigger mismetallation in both host and microbial enzymes if metal availability becomes too low or uneven.[14]
Cellular Defence Mechanisms Against Mismetallation
Mismetallation can lead to a range of cellular dysfunctions. To mitigate this risk, cells have evolved a variety of defence mechanisms to maintain metal homeostasis and ensure that metals are incorporated properly into their target proteins.[15] These mechanisms are crucial for preventing the deleterious effects of mismetallation, such as enzyme inactivation, oxidative stress, and protein misfolding.
| Mechanism | Description |
|---|---|
| Metallochaperones | Proteins that bind and transport specific metal ions to their target enzymes. These chaperones reduce the risk of incorrect metal binding, protecting against mismetallation by ensuring metals are delivered to the correct binding sites.[16] |
| Metal Transporters & Homeostasis Networks | Specialized proteins and transport systems regulate metal ion levels within the cell. Storage proteins like ferritin for iron and regulatory proteins control metal ion pools, preventing excessive accumulation of one metal and thus the potential for mismetallation.[17] |
| Antioxidant Systems | Oxidative stress can destabilize metal binding in enzymes. Antioxidant systems such as glutathione and catalase help limit ROS (reactive oxygen species) levels, thus preserving the integrity of metalloproteins and preventing their mismetallation by ensuring metals remain in their proper oxidative states.[18] |
Mismetallation and the Microbiome
The human microbiome, most especially in the gut, is a dense ecosystem of bacteria, archaea, fungi, and viruses that interact with host physiology. While direct mechanistic studies on mismetallation in the microbiome are still emerging, we know that metal exposure alters microbial composition and function, and microbial communities influence metal absorption and metabolism in the host.[19]
Metal-Microbiota Interactions
Heavy metals, such as lead and mercury, can disrupt the delicate balance of microbial populations (dysbiosis) in the gut.[20] These metals can alter microbial diversity and metabolism by affecting the growth of specific microbial species.[21] For instance, lead exposure has been shown to affect the Firmicutes:Bacteroidetes ratio in the gut, leading to alterations in nitrogen metabolism and overall microbial community structure.[22]
Microbial Metal Sequestration
Some microbes, especially those in the gut, are capable of sequestering metals, including toxic ones, through the production of metal-binding compounds (e.g., metallothioneins).[23] This sequestration limits the bioavailability of metals to the host, thus preventing the absorption of excess metals that could contribute to mismetallation in host cells. This process also reduces the risk of metal-induced toxicity in the body.
Microbiota and Metal Detoxification
Gut microbiota play a role in detoxifying harmful metals by transforming them into less toxic forms.[24] These microbial processes not only affect metal availability in the gut but also influence systemic metal homeostasis and prevent imbalances that could lead to mismetallation in the body.[25] Although the precise role of mismetallation in microbial enzymes is underexplored, it is likely that when microbial metal pools are disrupted, whether by dietary changes or environmental exposure, bacteria may exhibit altered metalloprotein function. This could affect microbial metabolism and survival, as well as their ability to interact with the host’s metal systems.
Heavy Metal Toxicities and Microbiome Dysbiosis
High environmental exposure to toxic metals (e.g., arsenic, lead, cadmium) can disrupt gut microbiota and contribute to metabolic and inflammatory diseases by altering metal utilization and microbiota function.[26] Mismetallation represents a subtle but widespread biochemical problem with implications across human physiology, cellular metabolism, ageing, immune function, and even gut microbiome ecology.[27] It is driven by oxidative stress, imbalanced metal homeostasis, environmental exposure, and genetic defects in metal handling. Cells counteract mismetallation with metallochaperones, regulatory networks, and antioxidant systems, but in disease contexts these systems can be overwhelmed. Understanding mismetallation more deeply offers new ways to approach diseases ranging from inherited copper disorders to neurodegeneration and microbiome‑linked chronic diseases. Continued research into metal homeostasis at the host–microbiome interface could reveal novel therapeutic targets and strategies to modulate metal‑associated pathologies
Research Feed
Metallation and mismetallation of iron and manganese proteins in vitro and in vivo: the class I ribonucleotide reductases as a case study
October 1, 2013
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The Role of Metal Ions in Enzyme Catalysis and Human Health
August 18, 2025
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Metal Preferences and Metallation
August 24, 2014
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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The Mismetallation of Enzymes during Oxidative Stress
August 26, 2014
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Moving metals: how microbes deliver metal cofactors to metalloproteins
July 5, 2023
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Metallochaperones: A critical regulator of metal homeostasis and beyond
February 17, 2022
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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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Cadmium induces iron deficiency anemia through the suppression of iron transport in the duodenum
July 6, 2020
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Heavy Metals Toxicity: Mechanism, Health Effects, and Therapeutic Interventions
August 19, 2025
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Cardiovascular Health •
Cardiovascular Health
Did you know?
Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) is strongly linked to cardiovascular disease, potentially influencing atherosclerosis more than cholesterol, making the gut microbiome a key therapeutic target.
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The Impact of Arsenic, Cadmium, Lead, Mercury, and Thallium Exposure on the Cardiovascular System and Oxidative Mechanisms in Children
June 25, 2025
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Cardiovascular Health •
Cardiovascular Health
Did you know?
Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) is strongly linked to cardiovascular disease, potentially influencing atherosclerosis more than cholesterol, making the gut microbiome a key therapeutic target.
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Lysosome-related Organelles as Mediators of Metal Homeostasis
August 26, 2014
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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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Parkinson-like wild-type superoxide dismutase 1 pathology induces nigral dopamine neuron degeneration in a novel murine model
March 5, 2025
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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The exploitation of nutrient metals by bacteria for survival and infection in the gut
October 30, 2025
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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How Toxic and Essential Metals Disrupt Gut Microbiota: A Comprehensive Review
Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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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Essential metals in health and disease
September 22, 2022
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Metallochaperones: Bind and Deliver
June 2, 2002
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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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Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking
December 10, 2024
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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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Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions
February 28, 2012
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Toxic and essential metals: metabolic interactions with the gut microbiota and health implications
July 29, 2024
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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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Metal(loid)-gut microbiota interactions and microbiota-related protective strategies: A review
September 18, 2024
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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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Lead exposure in relation to gut homeostasis, microbiota, and metabolites
July 3, 2025
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Metals •
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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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Bioremediation and Tolerance of Humans to Heavy Metals through Microbial Processes: a Potential Role for Probiotics?
August 21, 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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Update History
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.
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.
Lead (Pb)
Lead exposure has a profound effect on the microbiome, disrupting microbial diversity, immune responses, and contributing to the development of antimicrobial resistance (AMR). Understanding how Pb interacts with microbial communities and impacts host-pathogen dynamics is essential for clinicians to mitigate long-term health risks and improve treatment strategies.
Cadmium (Cd)
Cadmium (Cd) is a highly toxic heavy metal commonly found in industrial, agricultural, and environmental settings. Exposure to cadmium can occur through contaminated water, food, soil, and air, and it has been linked to a variety of health issues, including kidney damage, osteoporosis, and cancer. In agriculture, cadmium is often present in phosphate fertilizers and can accumulate in plants, entering the food chain. Its toxicity to living organisms makes cadmium a subject of regulatory concern worldwide, particularly in industrial waste disposal and environmental monitoring.
Arsenic (As)
Arsenic can disrupt both human health and microbial ecosystems. Its impact on the gut microbiome can lead to dysbiosis, which has been linked to increased disease susceptibility and antimicrobial resistance. Arsenic's ability to interfere with cellular processes, especially through its interaction with essential metals like phosphate and zinc, exacerbates these effects.
Nutritional Immunity
Nutritional immunity restricts metal access to pathogens, leveraging sequestration, transport, and toxicity to control infections and immunity.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Cardiovascular Health
Recent research has revealed that specific gut microbiota-derived metabolites are strongly linked to cardiovascular disease risk—potentially influencing atherosclerosis development more than traditional risk factors like cholesterol levels. This highlights the gut microbiome as a novel therapeutic target for cardiovascular interventions.
Trimethylamine N-Oxide (TMAO)
TMAO is a metabolite formed when gut bacteria convert dietary nutrients like choline and L-carnitine into trimethylamine (TMA), which is then oxidized in the liver to TMAO. This compound is linked to cardiovascular disease, as it promotes atherosclerosis, thrombosis, and inflammation, highlighting the crucial role of gut microbiota in influencing heart health.
Cardiovascular Health
Recent research has revealed that specific gut microbiota-derived metabolites are strongly linked to cardiovascular disease risk—potentially influencing atherosclerosis development more than traditional risk factors like cholesterol levels. This highlights the gut microbiome as a novel therapeutic target for cardiovascular interventions.
Trimethylamine N-Oxide (TMAO)
TMAO is a metabolite formed when gut bacteria convert dietary nutrients like choline and L-carnitine into trimethylamine (TMA), which is then oxidized in the liver to TMAO. This compound is linked to cardiovascular disease, as it promotes atherosclerosis, thrombosis, and inflammation, highlighting the crucial role of gut microbiota in influencing heart health.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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.
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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 Role of Metal Ions in Enzyme Catalysis and Human Health.. Ankur Kumar Sharma. (2025).. (International Journal of Contemporary Research in Multidisciplinary, 4(4), 560–569.)
- Metallation and mismetallation of iron and manganese proteins in vitro and in vivo: The class I ribonucleotide reductases as a case study.. Stubbe, J. (2012).. (Metallomics : Integrated Biometal Science, 4(10), 1020.)
- Metal Preferences and Metallation.. Foster, A. W., Osman, D., & Robinson, N. J. (2014).. (Journal of Biological Chemistry, 289(41), 28095-28103.)
- The Mismetallation of Enzymes during Oxidative Stress.. Imlay, J. A. (2014).. (The Journal of Biological Chemistry, 289(41), 28121.)
- Moving metals: How microbes deliver metal cofactors to metalloproteins.. Kunkle, D. E., & Skaar, E. P. (2023).. (Molecular Microbiology, 120(4), 547.)
- The Mismetallation of Enzymes during Oxidative Stress.. Imlay, J. A. (2014).. (The Journal of Biological Chemistry, 289(41), 28121.)
- The Mismetallation of Enzymes during Oxidative Stress.. Imlay, J. A. (2014).. (The Journal of Biological Chemistry, 289(41), 28121.)
- Metallochaperones: A critical regulator of metal homeostasis and beyond.. Rono, J. K., Sun, D., & Yang, Z. M. (2022).. (Gene, 822, 146352.)
- Cadmium induces iron deficiency anemia through the suppression of iron transport in the duodenum.. Fujiwara, Y., Lee, J., Banno, H., Imai, S., Tokumoto, M., Hasegawa, T., Seko, Y., Nagase, H., & Satoh, M. (2020).. (Toxicology Letters, 332, 130-139.)
- Heavy Metals Toxicity: Mechanism, Health Effects, and Therapeutic Interventions.. Chen, C., & Zhang, F. (2025).. (MedComm, 6(9), e70241. https://doi.org/10.1002/mco2.70241)
- The Impact of Arsenic, Cadmium, Lead, Mercury, and Thallium Exposure on the Cardiovascular System and Oxidative Mechanisms in Children.. Wróblewski, M., Miłek, J., Godlewski, A., & Wróblewska, J. (2025).. (Current Issues in Molecular Biology, 47(7), 483.)
- Lysosome-related Organelles as Mediators of Metal Homeostasis.. Blaby-Haas, C. E., & Merchant, S. S. (2014).. (The Journal of Biological Chemistry, 289(41), 28129.)
- Parkinson-like wild-type superoxide dismutase 1 pathology induces nigral dopamine neuron degeneration in a novel murine model.. Abdeen, A. H., Trist, B. G., Nikseresht, S., Harwood, R., Roudeau, S., Rowlands, B. D., Kreilaus, F., Cottam, V., Mor, D., Richardson, M., Siciliano, J., Forkgen, J., Schaffer, G., Genoud, S., Li, A. A., Proschogo, N., Antonio, B., Falkenberg, G., Brueckner, D., . . . Double, K. L. (2025).. (Acta Neuropathologica, 149(1), 22.)
- The exploitation of nutrient metals by bacteria for survival and infection in the gut.. Bushman SD, Skaar EP (2025). (PLoS Pathog 21(10): e1013580.)
- Essential metals in health and disease.. Jomova, K., Makova, M., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., Rhodes, C. J., & Valko, M. (2022).. (Chemico-Biological Interactions, 367, 110173.)
- Metallochaperones: Bind and Deliver.. Rosenzweig, A.C. (2002).. (Chemistry & Biology, 9(6), 673–677.)
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking. Daiana A. Capdevila, Johnma J. Rondón, Katherine A. Edmonds, Joseph S. Rocchio, Matias Villarruel Dujovne, and David P. Giedroc. (Chemical Reviews 2024 124 (24), 13574-13659)
- Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions.. Lushchak, V. I. (2012).. (Journal of Amino Acids, 2012, 736837.)
- Toxic and essential metals: Metabolic interactions with the gut microbiota and health implications.. Zhu, Q., Chen, B., Zhang, F., Zhang, B., Guo, Y., Pang, M., Huang, L., & Wang, T. (2024).. (Frontiers in Nutrition, 11, 1448388.)
- Toxic and essential metals: Metabolic interactions with the gut microbiota and health implications.. Zhu, Q., Chen, B., Zhang, F., Zhang, B., Guo, Y., Pang, M., Huang, L., & Wang, T. (2024).. (Frontiers in Nutrition, 11, 1448388.)
- Metal(loid)-gut microbiota interactions and microbiota-related protective strategies: A review.. Peng, Z., Liao, Y., Yang, W., & Liu, L. (2024).. (Environment International, 192, 109017.)
- Lead exposure in relation to gut homeostasis, microbiota, and metabolites.. Tao, Y., Liu, D., Shi, Q., Sun, Q., Liu, C., & Zeng, X. (2025).. (Applied and Environmental Microbiology, 91(7), e00372-25.)
- Bioremediation and Tolerance of Humans to Heavy Metals through Microbial Processes: A Potential Role for Probiotics?. Monachese, M., Burton, J. P., & Reid, G. (2012).. (Applied and Environmental Microbiology, 78(18), 6397.)
- Metal(loid)-gut microbiota interactions and microbiota-related protective strategies: A review.. Peng, Z., Liao, Y., Yang, W., & Liu, L. (2024).. (Environment International, 192, 109017.)
- Toxic and essential metals: Metabolic interactions with the gut microbiota and health implications.. Zhu, Q., Chen, B., Zhang, F., Zhang, B., Guo, Y., Pang, M., Huang, L., & Wang, T. (2024).. (Frontiers in Nutrition, 11, 1448388.)
- Lead exposure in relation to gut homeostasis, microbiota, and metabolites.. Tao, Y., Liu, D., Shi, Q., Sun, Q., Liu, C., & Zeng, X. (2025).. (Applied and Environmental Microbiology, 91(7), e00372-25.)
- The Mismetallation of Enzymes during Oxidative Stress.. Imlay, J. A. (2014).. (The Journal of Biological Chemistry, 289(41), 28121.)
Ankur Kumar Sharma. (2025).
The Role of Metal Ions in Enzyme Catalysis and Human Health.International Journal of Contemporary Research in Multidisciplinary, 4(4), 560–569.
Read ReviewStubbe, J. (2012).
Metallation and mismetallation of iron and manganese proteins in vitro and in vivo: The class I ribonucleotide reductases as a case study.Metallomics : Integrated Biometal Science, 4(10), 1020.
Read ReviewFoster, A. W., Osman, D., & Robinson, N. J. (2014).
Metal Preferences and Metallation.Journal of Biological Chemistry, 289(41), 28095-28103.
Read ReviewImlay, J. A. (2014).
The Mismetallation of Enzymes during Oxidative Stress.The Journal of Biological Chemistry, 289(41), 28121.
Read ReviewKunkle, D. E., & Skaar, E. P. (2023).
Moving metals: How microbes deliver metal cofactors to metalloproteins.Molecular Microbiology, 120(4), 547.
Read ReviewImlay, J. A. (2014).
The Mismetallation of Enzymes during Oxidative Stress.The Journal of Biological Chemistry, 289(41), 28121.
Read ReviewImlay, J. A. (2014).
The Mismetallation of Enzymes during Oxidative Stress.The Journal of Biological Chemistry, 289(41), 28121.
Read ReviewRono, J. K., Sun, D., & Yang, Z. M. (2022).
Metallochaperones: A critical regulator of metal homeostasis and beyond.Gene, 822, 146352.
Read ReviewFujiwara, Y., Lee, J., Banno, H., Imai, S., Tokumoto, M., Hasegawa, T., Seko, Y., Nagase, H., & Satoh, M. (2020).
Cadmium induces iron deficiency anemia through the suppression of iron transport in the duodenum.Toxicology Letters, 332, 130-139.
Read ReviewChen, C., & Zhang, F. (2025).
Heavy Metals Toxicity: Mechanism, Health Effects, and Therapeutic Interventions.MedComm, 6(9), e70241. https://doi.org/10.1002/mco2.70241
Read ReviewWróblewski, M., Miłek, J., Godlewski, A., & Wróblewska, J. (2025).
The Impact of Arsenic, Cadmium, Lead, Mercury, and Thallium Exposure on the Cardiovascular System and Oxidative Mechanisms in Children.Current Issues in Molecular Biology, 47(7), 483.
Read ReviewBlaby-Haas, C. E., & Merchant, S. S. (2014).
Lysosome-related Organelles as Mediators of Metal Homeostasis.The Journal of Biological Chemistry, 289(41), 28129.
Read ReviewAbdeen, A. H., Trist, B. G., Nikseresht, S., Harwood, R., Roudeau, S., Rowlands, B. D., Kreilaus, F., Cottam, V., Mor, D., Richardson, M., Siciliano, J., Forkgen, J., Schaffer, G., Genoud, S., Li, A. A., Proschogo, N., Antonio, B., Falkenberg, G., Brueckner, D., . . . Double, K. L. (2025).
Parkinson-like wild-type superoxide dismutase 1 pathology induces nigral dopamine neuron degeneration in a novel murine model.Acta Neuropathologica, 149(1), 22.
Read ReviewBushman SD, Skaar EP (2025)
The exploitation of nutrient metals by bacteria for survival and infection in the gut.PLoS Pathog 21(10): e1013580.
Read ReviewJomova, K., Makova, M., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., Rhodes, C. J., & Valko, M. (2022).
Essential metals in health and disease.Chemico-Biological Interactions, 367, 110173.
Read ReviewRosenzweig, A.C. (2002).
Metallochaperones: Bind and Deliver.Chemistry & Biology, 9(6), 673–677.
Read ReviewDaiana A. Capdevila, Johnma J. Rondón, Katherine A. Edmonds, Joseph S. Rocchio, Matias Villarruel Dujovne, and David P. Giedroc
Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal TraffickingChemical Reviews 2024 124 (24), 13574-13659
Read ReviewLushchak, V. I. (2012).
Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions.Journal of Amino Acids, 2012, 736837.
Read ReviewZhu, Q., Chen, B., Zhang, F., Zhang, B., Guo, Y., Pang, M., Huang, L., & Wang, T. (2024).
Toxic and essential metals: Metabolic interactions with the gut microbiota and health implications.Frontiers in Nutrition, 11, 1448388.
Read ReviewZhu, Q., Chen, B., Zhang, F., Zhang, B., Guo, Y., Pang, M., Huang, L., & Wang, T. (2024).
Toxic and essential metals: Metabolic interactions with the gut microbiota and health implications.Frontiers in Nutrition, 11, 1448388.
Read ReviewPeng, Z., Liao, Y., Yang, W., & Liu, L. (2024).
Metal(loid)-gut microbiota interactions and microbiota-related protective strategies: A review.Environment International, 192, 109017.
Read ReviewTao, Y., Liu, D., Shi, Q., Sun, Q., Liu, C., & Zeng, X. (2025).
Lead exposure in relation to gut homeostasis, microbiota, and metabolites.Applied and Environmental Microbiology, 91(7), e00372-25.
Read ReviewMonachese, M., Burton, J. P., & Reid, G. (2012).
Bioremediation and Tolerance of Humans to Heavy Metals through Microbial Processes: A Potential Role for Probiotics?Applied and Environmental Microbiology, 78(18), 6397.
Read ReviewPeng, Z., Liao, Y., Yang, W., & Liu, L. (2024).
Metal(loid)-gut microbiota interactions and microbiota-related protective strategies: A review.Environment International, 192, 109017.
Read ReviewZhu, Q., Chen, B., Zhang, F., Zhang, B., Guo, Y., Pang, M., Huang, L., & Wang, T. (2024).
Toxic and essential metals: Metabolic interactions with the gut microbiota and health implications.Frontiers in Nutrition, 11, 1448388.
Read ReviewTao, Y., Liu, D., Shi, Q., Sun, Q., Liu, C., & Zeng, X. (2025).
Lead exposure in relation to gut homeostasis, microbiota, and metabolites.Applied and Environmental Microbiology, 91(7), e00372-25.
Read ReviewImlay, J. A. (2014).
The Mismetallation of Enzymes during Oxidative Stress.The Journal of Biological Chemistry, 289(41), 28121.
Read Review