Metallomics Reviews
Heavy Metals and Gut Microbiota: A Systematic Review
Clinical Overview
This systematic review synthesizes 12 human observational studies linking exposure to arsenic, lead, mercury, and cadmium with gut microbiota composition across pregnancy, infancy, childhood, and adulthood. Across matrices (urine, blood, drinking water, feces, hair, toenails, teeth), higher metal burdens consistently associated with dysbiosis, notably increased Collinsella and Proteobacteria and decreased Bifidobacterium and key Bacteroides taxa. Mercury speciation (methylmercury, inorganic Hg, total Hg) showed distinct associations with Firmicutes and specific genera. Although clinical endpoints were sparse, authors highlight plausible links to leaky gut, oxidative stress, metabolic disease, and inflammation, and propose dietary fiber, antioxidant-rich diets, and probiotics as mitigation strategies.
What was reviewed and who was studied
The authors systematically reviewed human cohort, cross-sectional, longitudinal, and nested case–control studies examining major heavy metal exposure (arsenic, lead, mercury, cadmium) and gut microbiota composition, excluding animal and interventional work. Populations included pregnant women, infants, children, and adults in the USA, China, Nepal, and Bangladesh, with metals assessed largely by ICP-MS from biological samples or water and microbiota characterized by fecal 16S rRNA sequencing or metagenomics.
Major findings
| Domain | Summary of findings |
|---|---|
| Arsenic (As) | Five studies showed As in urine, water, or toenails associated with altered gut composition. High As increased Collinsella, Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and As-resistant Escherichia coli, while reducing Erysipelotrichi/Erysipelotrichaceae and Catenibacterium. Associations with Ruminococcus and Clostridiaceae were metal- and age-dependent, and Bifidobacterium generally decreased except where high zinc co-occurred with As. |
| Lead (Pb) | Five studies reported that prenatal and early-life Pb, often reconstructed from teeth or maternal blood, reduced multiple beneficial taxa (e.g., Bifidobacterium bifidum/longum, several Bacteroides OTUs, Alistipes, Coprococcus, Ruminococcus species) and increased Collinsella, Bilophila, and fungal Malassezia species. Adult urinary Pb correlated positively with Proteobacteria and Burkholderiales. Some studies found no significant associations. |
| Mercury (Hg; THg, MeHg, IHg) | Four studies assessed total Hg, methylmercury, and inorganic Hg in feces, hair, blood, and meconium. Higher MeHg and THg generally increased Firmicutes, whereas IHg showed negative relations with some Firmicutes. Rice-derived Hg exposure was linked to reduced Proteobacteria/Gammaproteobacteria but increased Desulfovibrio and methanogens; low Hg via fish versus rice also raised Actinobacteria, Desulfovibrio, and methanogens. MeHg and IHg correlated positively with Collinsella, Ruminococcaceae, Lachnospiraceae, Faecalibacterium, and Parabacteroides in pregnancy, with gestation-specific patterns. |
| Cadmium (Cd) | A single high-quality cross-sectional study in US infants found moderate Cd in toenails positively associated with Bifidobacterium abundance, without broader community reporting, limiting interpretation. |
| Microbiota–health links | One Bangladeshi cohort examining As exposure and carotid intima-media thickness reported no significant associations between specific taxa (e.g., RF3, Epsilonproteobacteria, Campylobacterales, Anaerostipes, Faecalibacterium) and atherosclerosis, and most studies did not directly link microbial changes to hard clinical outcomes. |
| Nutritional context | The discussion integrates evidence that Collinsella overgrowth relates to leaky gut, metabolic disorders, and low dietary fiber intake, and that dietary fiber, antioxidant-rich foods, probiotics, prebiotics, and adequate micronutrients (e.g., iron, zinc) may mitigate heavy-metal-induced dysbiosis and toxicity, positioning nutrition as a modifiable co-determinant of the metallome–microbiome interface. |
Implications for Microbial Metallomics
This review situates human heavy metal exposure as a modifier of the intestinal metallome that reshapes microbial ecology, particularly pathobiont enrichment and loss of beneficial saccharolytic taxa across life stages.
| Concept | Implication |
|---|---|
| Collinsella enrichment with As, Pb, and Hg | Collinsella emerges as a recurrent pathobiont signal of higher metal burden, mechanistically linked in the discussion to leaky gut, oxidative stress, and metabolic endotoxemia, suggesting a potential microbial biomarker of metal-associated intestinal barrier injury. |
| Proteobacteria and Enterobacteriaceae expansion under As and Pb | Metal-related increases in Proteobacteria, Gammaproteobacteria, and Enterobacteriaceae, including As-resistant E. coli, indicate selection for metal-tolerant, inflammatory taxa, providing an ecological readout of chronic environmental exposure and potential diagnostic signature of pro-inflammatory metallomic states. |
| Loss of Bifidobacterium and key Bacteroides with As and Pb | Depletion of Bifidobacterium and several Bacteroides OTUs in infants and children suggests disruption of early-life colonization trajectories, with consequences for SCFA production, immune education, and xenobiotic detoxification capacity. |
| Hg speciation (MeHg, IHg, THg) and Firmicutes/Ruminococcaceae patterns | Distinct associations of MeHg and IHg with Firmicutes, Lachnospiraceae, Ruminococcaceae, and Faecalibacterium during pregnancy highlight that oxidation state and source (rice versus fish) shape metallome–microbiome interactions, underscoring the need to measure speciation, not just total Hg. |
| Cd and Bifidobacterium in infants | The positive association between moderate Cd and Bifidobacterium hints that low–moderate Cd may interact with co-exposures (e.g., nutrients) in non-linear ways, emphasizing the importance of mixture models that integrate essential and toxic elements when interpreting gut metallomics. |
| Nutritional modulation of metal–microbiome effects | The authors’ emphasis on fiber, antioxidant-rich diets, probiotics, prebiotics, and micronutrient sufficiency frames the gut metallome as nutritionally tunable, suggesting combined dietary and microbial interventions as future strategies for mitigating metal-related dysbiosis. |
Limitations
The evidence base is small and uneven across metals, with no eligible aluminium studies and only one cadmium paper. Many studies are cross-sectional, limiting causal inference, and populations, matrices, exposure levels, and geographic settings are heterogeneous. Adjustment for co-exposure to other metals and relevant covariates is incomplete, and microbiota outcomes and taxa reporting are not standardized, precluding meta-analysis or definitive quantitative thresholds.
Future perspectives
The authors’ synthesis supports several next steps. Larger, harmonized longitudinal cohorts should quantify mixtures of essential and toxic elements (including speciation for Hg and potentially As) alongside standardized fecal sequencing to resolve temporal dynamics. Integrating maternal, infant, and child data will clarify critical windows of susceptibility. Focused analyses on recurrent taxa such as Collinsella, Proteobacteria, and Bifidobacterium may yield candidate biomarkers of metal burden and dysbiosis. Nutritional and probiotic/prebiotic interventions, explicitly designed around metal exposure levels and dietary patterns, are logical translational trials to test whether modulating the gut metallome can attenuate barrier dysfunction and systemic toxicity.
Key takeaways for Researchers and Clinicians
Across human populations in the USA, China, Nepal, and Bangladesh, this review links higher arsenic, lead, and mercury exposure—with limited data for cadmium—to reproducible gut microbiome shifts: expansion of Collinsella and Proteobacteria, reduced Bifidobacterium and Bacteroides, and Hg-speciation–specific changes in Firmicutes and Ruminococcaceae. Direct clinical outcomes were rarely measured, but the authors integrate these patterns with literature on leaky gut, metabolic disease, and inflammatory conditions, particularly in vulnerable windows such as pregnancy and early infancy.
Methodologically, the work highlights ICP-MS-based multi-matrix exposure assessment, hair/teeth as developmental archives, and 16S rRNA or metagenomic profiling as core tools for clinical metallomics. Clinically, the paper argues for reducing environmental metal exposure while leveraging dietary fiber, antioxidant-rich foods, probiotics, and micronutrient repletion to buffer gut barrier damage and dysbiosis. A concise translational hook is that Collinsella-centric, metal-linked dysbiosis may become a measurable interface between environmental regulation, nutritional policy, and microbiome-informed preventive care.
Citation
Rezazadegan M, Forootani B, Hoveyda Y, Rezazadegan N, Amani R. Major heavy metals and human gut microbiota composition: a systematic review with nutritional approach. J Health Popul Nutr. 2025;44:21. doi:10.1186/s41043-025-00750-4