Heavy metals: toxicity and human health effects Original paper

What was reviewed?

This narrative review synthesizes mechanistic and toxicological evidence on heavy metals and human health, with a particular focus on how protein-binding competition and redox disruption converge on gut–immune pathways relevant to dysbiosis. To ensure the focus remains clinically meaningful for microbiome work, the review tracks how aluminum, cadmium, arsenic, mercury, lead, and chromium perturb antioxidant defenses, displace essential metals at enzyme and transporter sites, and impair epithelial integrity, mechanisms that link heavy metals and human health to shifts in microbial ecology, lipopolysaccharide (LPS) translocation, and mucosal inflammation.

Who was reviewed?

Evidence spans occupationally and environmentally exposed humans, in vivo rodent models, and cellular systems that clarify organ- and pathway-specific toxicity. The review aggregates data across inhalational, oral, and dermal exposures, emphasizing intestinal, renal, pulmonary, cardiovascular, and neurobehavioral endpoints. It also details redox signaling nodes (e.g., NF-κB, Nrf2) and host metal-handling proteins (e.g., metallothioneins, transferrin) that mediate the host–microbe consequences of exposure.

Most important findings

Heavy metals disrupt redox balance by binding thiols on antioxidant enzymes (SOD, catalase, GPx) and by displacing essential metals (Fe, Cu, Zn, Ca, Mg) at protein active sites, thereby amplifying reactive oxygen species through Fenton chemistry and impairing mitochondrial function. At the gut interface, aluminum and cadmium exemplify a shared path: epithelial tight-junction dysfunction, increased intestinal permeability, and heightened LPS trafficking that primes Kupffer cells and systemic cytokine responses (IL-1β, IL-6, TNF-α), all of which are consistent with a dysbiotic shift away from probiotic taxa toward opportunistic/pathobiont profiles. In murine colitis models, aluminum exposure intensifies and prolongs inflammation, increases colonic myeloperoxidase activity, suppresses epithelial renewal, and upregulates NF-κB signaling with downstream MMP-9 expression—findings that map to microbiome-linked exacerbation of barrier injury and inflammatory bowel disease phenotypes.

Cadmium further demonstrates microbiome-relevant toxicity via Nrf2- and p62-modulated autophagy flux, mitochondrial complex II/III inhibition, and ion-transport derangements that alter luminal electrolytes and epithelial energetics, conditions that can select for stress-tolerant, inflammation-associated microbes. Across organs, the same protein-binding competition and redox injury that shape the intestinal milieu also drive renal tubular dysfunction (low-molecular-weight proteinuria, glycosuria), pulmonary inflammation and remodeling (airway wall thickening, macrophage M1 polarization), and atherosclerosis-promoting lipid disturbances, each accompanied by cytokine patterns that reinforce microbe–immune crosstalk. Collectively, these data nominate host redox and metal-handling pathways as primary drivers linking exposure to clinically meaningful microbiome signatures, barrier failure, endotoxemia, and inflammation-prone community states.

Key implications

For clinicians integrating microbiome insights, the review supports considering heavy-metal exposure as a modifiable upstream determinant of dysbiosis, especially in patients with IBD, chronic liver disease, chronic kidney disease, or cardiometabolic comorbidity. Practical takeaways include maintaining vigilance for exposure histories (occupational aerosols, contaminated food/water), recognizing biomarker constellations consistent with endotoxemia and oxidative stress (elevated CRP, cytokines, myeloperoxidase), and understanding that chelation—where clinically appropriate—targets a root driver of barrier damage and microbe–immune activation rather than downstream inflammation alone. The mechanistic emphasis on NF-κB/MMP-9, Nrf2, metallothioneins, and mitochondrial injury provides tractable nodes for aligning exposure mitigation with microbiome-sensitive care pathways.