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
Researched by:
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Karen Pendergrass
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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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Kimberly Eyer
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Kimberly Eyer
Kimberly 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.
Research feed -
Karen Pendergrass
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Fact-checked by:
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Kimberly Eyer
ID
Kimberly Eyer
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 
Research Feed Overview
Heavy metals, both essential and non-essential, play a significant role in microbial physiology and influence the gut microbiome, impacting both microbial composition and host health. [x] Transition metals like iron, zinc, copper, nickel, and manganese are crucial for the enzymatic machinery of organisms, but their imbalance can foster pathogenic environments within the gastrointestinal tract. [x] This review examines how heavy metals impact the gut microbiome, explores the mechanisms of bacterial metal homeostasis, and discusses the implications for human health.
Metal Homeostasis and Microbial Physiology
Bacteria maintain metal homeostasis to cope with fluctuating metal levels. They acquire, balance, and regulate transition metals, ensuring proper cofactoring of metal-dependent enzymes. Regulatory mechanisms allow bacteria to sense metal concentrations and adjust gene expression, vital for survival under varying metal conditions. Efficient metal homeostasis enhances microbial virulence, enabling pathogens to outcompete host mechanisms like nutritional immunity.
Impact of Heavy Metals on the Gut Microbiome
Heavy metals, both essential and non-essential, reshape the gastrointestinal microbiome through diverse mechanisms. Excessive essential metals disrupt microbial balance, favoring pathogenic bacteria over commensals, while non-essential metals like arsenic and lead, even at lower levels, profoundly impact microbial diversity and function. [x] Additionally, heavy metal exposure, such as arsenic, prompts adaptive responses in the microbiome, selecting for metal-resistant bacteria, thus altering the gut’s microbial composition and health dynamics.
What heavy metals are utilized by pathogenic microbes?
| Heavy Metal | Utilization by Pathogenic Microbe |
|---|---|
| Iron | Salmonella enterica uses siderophores to scavenge iron from the host, enhancing its virulence. |
| Zinc | Staphylococcus aureus uses zinc uptake regulator (Zur) to manage its zinc needs, contributing to its survival in the host. |
| Copper | Mycobacterium tuberculosis resists copper toxicity through copper efflux systems, aiding in its persistence. |
| Mercury | Clostridium difficile may utilize mercury resistance genes to survive in mercury-rich environments. |
| Nickel | Helicobacter pylori utilizes nickel-dependent enzymes like hydrogenase and urease for energy production and to neutralize gastric acid, enhancing its survival in the stomach. Salmonella Typhimurium relies on nickel for the function of its hydrogenases, crucial for survival within macrophages. |
What health conditions are associated with metal homeostasis disruptions?
| Health Condition | Associated Metal Homeostasis Disruption |
|---|---|
| Multiple Sclerosis | Linked with disturbances in zinc and copper homeostasis, influencing disease progression. |
| Endometriosis | Associated with disruptions in iron and nickel homeostasis, potentially driving disease pathology through oxidative stress. |
| Neurodegenerative Diseases | Imbalances in copper, iron, and zinc are implicated in diseases like Alzheimer’s and Parkinson’s. |
| Cardiovascular Diseases | Dysregulation of copper and iron metabolism can contribute to cardiovascular pathologies such as atherosclerosis. |
Therapeutic Implications
Understanding the intricacies of metal homeostasis in microbes offers valuable insights for developing novel therapeutic strategies. Targeting metal uptake systems or efflux mechanisms presents opportunities to combat infections by disrupting crucial microbial processes. Such strategies highlight the potential of leveraging metal homeostasis for therapeutic gains. In conclusion, the dynamic interplay between heavy metals and the gut microbiome significantly affects human health. By advancing our understanding of microbial metal acquisition and the impacts of metal exposure, we can better manage diseases associated with dysbiosis and develop targeted treatments that modify the gut microbiome.
Research Feed
Copper in microbial pathogenesis: meddling with the metal
This study explores the dual role of copper in microbial pathogenesis, highlighting how it serves both as a vital nutrient and a potent antimicrobial agent. The research delves into the sophisticated mechanisms developed by pathogens, like Mycobacterium tuberculosis and Pseudomonas aeruginosa, to evade copper's toxicity, including specialized copper pumps and regulatory proteins. It also investigates copper's critical role in the host's immune defense, influencing infection outcomes. Findings suggest that copper's antimicrobial properties could be leveraged in healthcare to develop new treatment strategies, and its application in environmental settings could help control pathogen growth.
What was studied?
The study investigated the role of copper in microbial pathogenesis. Specifically, it examined how copper serves as both a necessary nutrient for microbial organisms and a microbial weapon used by hosts against pathogens. The research explored copper’s dual roles, its involvement in various microbial resistance mechanisms, and its interaction with the host’s immune responses.
Who was studied?
The study focused on various microbial species, including bacteria and fungi. It delved into the copper homeostasis mechanisms of pathogens like Mycobacterium tuberculosis and Pseudomonas aeruginosa, and also examined model organisms such as Saccharomyces cerevisiae to understand copper’s role in microbial pathogenesis and resistance.
What were the most important findings?
Significant findings from the study demonstrate that copper is utilized by hosts as an antimicrobial agent, significantly impacting pathogen growth and survival. Additionally, pathogens have evolved sophisticated mechanisms to counteract copper toxicity. These adaptations include the development of specific copper pumps and regulatory proteins that meticulously manage copper uptake and expulsion. Moreover, copper is found to play a critical role in the immune defense strategy of hosts, substantially influencing the outcomes of infections. These insights underscore the complex interplay between copper, pathogens, and host defenses.
What are the greatest implications of this study?
The implications of this research are broad and significant for both healthcare and environmental management. Understanding copper’s role in microbial pathogenesis could lead to the development of new antimicrobial strategies and treatments that leverage copper’s toxic effects on pathogens. Additionally, this knowledge could inform the use of copper in medical and environmental applications to control pathogen growth, thereby reducing infection rates and enhancing public health safety.
Influence of heavy metal exposure on gut microbiota: Recent advances
This review highlights that heavy metal exposure disrupts gut microbiota composition and function, leading to dysbiosis and various health implications. Heavy metals alter gene expression in both the host and microbiota, affecting immune regulation and oxidative stress pathways. Dysbiosis induced by heavy metals can lead to inflammation, gut motility disturbances, and increased susceptibility to diseases like inflammatory bowel diseases. The study underscores the importance of understanding heavy metal-induced dysbiosis and its implications for human and environmental health, advocating for further research in this area.
What was studied?
The study investigated the impact of heavy metal exposure on the composition and function of gut microbiota. Specifically, it looked at how heavy metals such as arsenic, cadmium, lead, and mercury affect the diversity, richness, and metabolism of gut bacteria.
Who was studied?
The research encompassed various model organisms, including humans, mice, rats, chickens, fish, crayfish, and asiatic toad. Studies were conducted on both adult and juvenile stages of these organisms to understand the effects of heavy metal exposure on gut microbiota across different life stages.
What were the most important findings?
Several significant findings have emerged from the study: Heavy metal exposure has been shown to induce dysbiosis in the gut microbiota, manifesting in alterations in microbial composition, gene expression, metabolism, and immune response. Moreover, the gut microbiota play a pivotal role in the detoxification and elimination of heavy metals, facilitated through enzymatic reactions, bioaccumulation, and methylation processes. Notably, exposure to heavy metals results in shifts in the abundance of specific bacterial phyla within the gut microbiome, including Proteobacteria, Firmicutes, and Bacteroidetes. These alterations in gut microbiota composition and function have far-reaching health implications, including oxidative stress, neurobehavioral damage, disrupted lipid metabolism, compromised immune function, and heightened susceptibility to inflammatory bowel diseases.
What are the greatest implications of this study?
The study underscores several important implications: It stresses the criticality of comprehending how heavy metals affect gut microbiota, as this knowledge is essential for evaluating the environmental and public health risks linked to heavy metal exposure. Moreover, the findings advocate for the development of guidelines and interventions aimed at mitigating heavy metal-induced toxicity and safeguarding gut microbiota health. Further research is imperative to uncover the mechanisms behind heavy metal-induced dysbiosis of gut microbiota and its repercussions on human health, necessitating investigations into microbial alterations at the species and strain levels using advanced sequencing methodologies like metagenomics. Additionally, epidemiological studies involving human populations are warranted to directly assess the health consequences of heavy metal exposure on gut microbiota and to guide the formulation of preventive measures and public health policies.
Urinary lead concentration and composition of the adult gut microbiota in a cross-sectional population-based sample
This study explores the link between urinary lead concentration and adult gut microbiota composition. Conducted on 696 participants, it reveals associations between lead levels and increased microbial diversity and richness. Specific bacterial groups, like Proteobacteria, correlate with elevated lead.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.