How Toxic and Essential Metals Disrupt Gut Microbiota: A Comprehensive Review Original paper

What was reviewed?

This review article investigates the bidirectional interactions between toxic and essential metals and the gut microbiota, synthesizing evidence on how these interactions influence host metabolic, immunologic, and physiologic outcomes. The paper categorizes ten common heavy metals including arsenic (As), mercury (Hg), lead (Pb), cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), chromium (Cr), silicon (Si), and nickel (Ni) based on their essentiality and toxicity. It compiles data from over 100 experimental studies across animal models and some human cohorts, highlighting how these metals alter microbial diversity, abundance, and metabolic output, and conversely, how gut microbes can modulate metal toxicity, bioavailability, and systemic absorption.

Who was reviewed?

The review synthesizes findings from studies involving humans, rodents (mice and rats), aquatic species (tilapia, zebrafish, crayfish), birds (budgerigars), and insects (bees), as well as in vitro models such as the SHIME (Simulated Human Intestinal Microbial Ecosystem). These models provided diverse insights into host–metal–microbiota interactions across species and life stages.

Most important findings

The review establishes that exposure to toxic heavy metals (THMs) like As, Hg, Pb, Ni, and Cd leads to gut dysbiosis characterized by decreased alpha diversity, disrupted SCFA production, and increased pro-inflammatory cytokines. Arsenic exposure, for instance, consistently elevated Bacteroidetes while suppressing Firmicutes, and perturbed bile acid metabolism. Mercury exposure altered gut-brain and gut-liver metabolites and enriched taxa such as Coprococcus and Oscillospira while suppressing Lactobacillaceae. Lead exposure decreased Ruminococcus and increased Proteobacteria and Succinivibrionaceae, linking microbial shifts to neurotoxicity and metabolic disorders. Cadmium increased pro-inflammatory genera like Helicobacter and Mycoplasma while decreasing protective Lactobacillus spp., impairing immune and reproductive functions.

Essential trace elements, while beneficial at physiological doses, caused microbial disturbances when in excess. High dietary Cu, Mn, or Fe exposure reduced probiotics like Lactobacillus, Bifidobacterium, and Akkermansia, and modulated bile acid, amino acid, and lipid metabolism. Notably, nickel exposure in both humans and mice reduced Lactobacillus and Blautia, increased uric acid, and worsened systemic inflammation. Chromium showed valence-dependent effects: trivalent Cr (Cr^3+) was beneficial, while hexavalent Cr (Cr^6+) promoted dysbiosis and tumorigenesis.

Microbial Taxa Altered by Heavy Metal Exposure

Below is a consolidated table summarizing bacterial taxa that have been reported to increase (↑) or decrease (↓) in relative abundance upon exposure to each of ten heavy metals. Each entry reflects significant changes observed in reviewed studies. Taxonomic ranks (phylum, family, genus, species) are listed as reported. If data for a metal were limited, the findings are correspondingly sparse.

Key implications

This review underscores the critical role of microbial metallomics in modulating human health outcomes. The gut microbiota is not only a target of metal-induced toxicity but also a mediator of metal detoxification. The composition of the microbiota determines the host’s susceptibility to metal-induced metabolic and immune dysfunction, with implications for conditions such as diabetes, cardiovascular disease, neurodegeneration, and cancer. The authors advocate for gender-stratified, multi-metal exposure studies and microbiome-targeted intervention strategies to mitigate health risks. This work directly supports the development of microbiome signatures for environmental metal exposure and the validation of microbiome-targeted detoxification interventions.