The Human Gut Microbiome’s Influence on Arsenic Toxicity Original paper

What was reviewed?

This review examined how the human gut microbiome and arsenic toxicity intersect, focusing on ways gut bacteria alter arsenic speciation, bioavailability, metabolism, and excretion. It summarized evidence that gut microbes reduce arsenate, efflux, and sequester arsenite via ars operons (ArsC, ArsB/Acr3, ArsA, ArsD), methylate arsenic through ArsM to mono- and dimethylated species, and generate thiolated and glutathione-conjugated forms that change toxicity. It also covered ex vivo human stool incubations showing microbiome-driven conversion of pentavalent species into more toxic trivalent organoarsenicals, animal studies linking microbiome disruption to higher body burdens, and population studies connecting exposure with shifts in community structure and resistance genes.

Who was reviewed?

The authors synthesized culture studies of gut and environmental bacteria, ex vivo work with human fecal samples, gnotobiotic and antibiotic-perturbed mouse models (including humanized AS3MT-knockout mice), and limited human epidemiology. The authors discussed US infant cohorts where urinary arsenic correlated with gains and losses in genera, Bangladeshi children where high household water arsenic enriched Enterobacteriaceae and resistance genes, and rodent experiments showing that even 10 ppb exposures shifted microbiome composition and host pathways. They also highlighted clinical angles around arsenic trioxide therapy, noting how patient microbiomes may influence oral bioavailability and toxicity, and called for epidemiologic studies that track microbiome function alongside arsenic speciation and health outcomes.

Most important findings

The microbiome can directly biotransform arsenic and change host exposure. Bacteria reduce arsenate to arsenite and pump it out, methylate arsenite to MMA and DMA, and, in low-oxygen gut settings, can favor more toxic trivalent organoarsenicals; stool incubations from humans produced MMA(III) and DMA(III) from pentavalent precursors. In vivo, microbiome depletion increases host arsenic load: antibiotic-treated mice showed reduced fecal excretion and greater hepatic and pulmonary accumulation, while colonization with commensals such as Faecalibacterium protected AS3MT-deficient mice. Arsenic itself perturbs gut communities in dose- and time-dependent ways, with reported enrichment of

Gammaproteobacteria/Enterobacteriaceae in exposed children and decreases in common commensals in animal models; sex, feeding status, and micronutrients modify these effects. Notably, arsenic exposure co-selects antibiotic and metal resistance genes, consistent with ars loci co-occurring on mobile elements. Across models, SCFA-producing taxa (e.g., Blautia, Lachnospiraceae, Ruminococcus, Faecalibacterium) tracked with better survival or lower toxicity, suggesting functional markers for a microbiome signatures database. Mechanistically, microbial redox chemistry, methylation, thiolation, and adsorption to Gram-positive extracellular polymers emerge as key routes by which microbes lower or raise the effective dose at the mucosa and shape urinary speciation profiles relevant to clinical risk.

Key implications

Clinicians should factor microbiome status into arsenic risk assessment and care. Unnecessary antibiotics may raise tissue burdens by stripping biomass that binds or transforms arsenic, while diets that support SCFA producers could help restore barrier function and detox pathways. Iron sufficiency may blunt arsenic-driven dysbiosis, and zinc deficiency may worsen it, so basic nutrition matters in exposed patients. For monitoring and research, pair exposure metrics with microbiome readouts and arsenic speciation, since the same dose can yield different toxicity depending on gut community function. In oncology, as oral arsenic trioxide use expands, integrate stool microbiome profiling and recent antibiotic history into pharmacovigilance and PK/PD studies. Overall, the review argues for microbiome-aware public health and precision mitigation that combine source remediation with strategies to preserve or rebuild protective gut functions.