Karen Pendergrass is a researcher specializing microbial metallomics and microbiome signatures, with a focus on bridging research and clinical practice. She is the co-founder of several initiatives, including Microbiome Signatures and the Heavy Metal Tested & Certified program, which translate complex science into actionable standards. 
Karen Pendergrass is a researcher specializing microbial metallomics and microbiome signatures, with a focus on bridging research and clinical practice. She is the co-founder of several initiatives, including Microbiome Signatures and the Heavy Metal Tested & Certified program, which translate complex science into actionable standards. Overview
This comprehensive review examines the metabolic interactions between ten common heavy metals—including toxic heavy metals (THMs) such as arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd), and essential trace elements like iron (Fe), copper (Cu), and manganese (Mn)—and the gut microbiota. The review summarizes how both toxic and essential metals influence the composition, diversity, and metabolic functions of the gut microbiome, and, reciprocally, how the gut microbiota modulates the absorption, metabolism, and toxicity of these metals. The analysis incorporates data from in vivo and in vitro studies across multiple species (humans, rodents, fish, birds, and insects), focusing on the bidirectional relationship and the resulting health implications, including metabolic, inflammatory, neurological, and immune disorders. Special attention is given to the consequences of both deficiencies and excesses of essential trace elements, and the additive, synergistic, or antagonistic effects of combined metal exposures, reflecting real-world environmental and dietary exposures.
Who was reviewed?
The review aggregates findings from a broad spectrum of research involving human cohorts, various animal models (rodents, fish, birds, insects), and in vitro systems. These studies investigated the effects of single and combined exposures to heavy metals and trace elements on gut microbiota composition, metabolic pathways, and related health outcomes. Both clinical and epidemiological studies in humans, as well as controlled laboratory experiments in animals, are included. The review highlights population subgroups such as infants, children, and occupationally exposed adults, as well as special conditions such as high-fat diets, specific disease models (e.g., diabetes, cancer), and gender-specific effects.
Key Findings on Heavy Metals, Trace Elements, and the Gut Microbiota
The review highlights how both toxic heavy metals and essential trace elements can disrupt gut microbiota composition and function, with significant implications for host metabolism, immunity, and long-term health. These interactions are highly relevant to heavy metal certification and safety programs because they underscore the role of the gut microbiota as both a target and mediator of metal toxicity. The evidence also emphasizes the complexity of combined exposures, the promise of probiotic interventions, and the potential utility of microbiome biomarkers in certification frameworks.
| Finding | Details |
|---|---|
| Toxic Heavy Metals (THMs) | Arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd) disrupt gut microbiota diversity and metabolic activity, weakening gut barrier function. Linked to metabolic disorders, immune dysregulation, neurotoxicity, inflammation, and chronic disease risk. |
| Essential Trace Elements | Iron (Fe), copper (Cu), and manganese (Mn) are required in small amounts but toxic in excess. Elevated Cu reduces probiotics and impairs gut barrier integrity; Fe imbalance alters fatty acid metabolism, promotes pathogens, and drives inflammation; excess Mn is linked to neurotoxicity and neurotransmitter disruption. |
| Bidirectional Interactions | The gut microbiota can transform, detoxify, or accumulate metals, influencing their bioavailability and toxicity. Lactobacillus, Bifidobacterium, and Akkermansia mitigate toxicity via chelation, metabolic transformation, and gut barrier maintenance. |
| Combined Exposures | Multiple metals often co-occur in food and environment, producing additive, synergistic, or antagonistic effects. Examples include Cr and Ni, which jointly alter microbiota composition, metabolic pathways, and inflammatory outcomes. |
| Probiotic and Biomarker Strategies | Probiotics (conventional and next-generation) reduce absorption and mitigate toxicity. Microbial biomarkers show potential as indicators of exposure or early effect, supporting certification and monitoring. |
| Health Implications | Metal-induced microbiota disruptions are mechanistically linked to diabetes, cardiovascular disease, neurodegenerative conditions, cancer, and immune dysfunction, underscoring broad public health risks. |
Key implications
For heavy metal certification programs (such as HMTC), these findings underscore the necessity of considering not only direct toxicological thresholds but also the indirect and long-term health effects mediated by the gut microbiota. Regulatory standards should account for the complex interplay between metals and the microbiome, including the risks posed by mixtures, the potential for low-level chronic exposures to induce subtle but significant health outcomes, and the protective or mitigating role of specific microbial taxa. Certification protocols may benefit from incorporating assessments of microbiome health, the use of probiotic interventions, and the development of microbial or metabolic biomarkers to monitor exposure and effect. The review also highlights the importance of gender-specific and age-specific considerations, as well as the need to expand research into combined exposures and real-world scenarios to better inform safety standards and regulatory policies.
Citation
Zhu Q, Chen B, Zhang F, Zhang B, Guo Y, Pang M, Huang L, Wang T. Toxic and essential metals: metabolic interactions with the gut microbiota and health implications. Front Nutr. 2024;11:1448388. doi:10.3389/fnut.2024.1448388
Lead is a neurotoxic heavy metal with no safe exposure level. It contaminates food, consumer goods and drinking water, causing cognitive deficits, birth defects and cardiovascular disease. HMTC’s rigorous lead testing applies ALARA principles to protect infants and consumers and to prepare brands for tightening regulations.
Heavy metals are high-density elements that accumulate in the body and environment, disrupting biological processes. Lead, cadmium, arsenic, mercury, nickel, tin, aluminum, and chromium are of greatest concern due to persistence, bioaccumulation, and health risks, making them central to the HMTC program’s safety standards.
Lead is a neurotoxic heavy metal with no safe exposure level. It contaminates food, consumer goods and drinking water, causing cognitive deficits, birth defects and cardiovascular disease. HMTC’s rigorous lead testing applies ALARA principles to protect infants and consumers and to prepare brands for tightening regulations.
