The Effects of an Environmentally Relevant Level of Arsenic on the Gut Microbiome and Its Functional Metagenome Original paper
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Divine Aleru
I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
What was studied?
This original study tested how an environmentally relevant dose of arsenic changes the gut ecosystem and its gene functions in mice using a combined 16S rRNA and shotgun metagenomics approach. The authors exposed mice to 100 ppb arsenic in drinking water for 13 weeks and tracked shifts in community structure and pathways. The work centered on the arsenic gut microbiome functional metagenome, asking whether low-dose exposure lowers short-chain fatty acid (SCFA) capacity, raises inflammatory signals such as lipopolysaccharide (LPS), and selects for stress and resistance genes that could affect host health. The study also mapped specific taxa that rise or fall with exposure to support reproducible microbiome signatures.
Who was studied?
The team used specific-pathogen-free female C57BL/6 mice. They first normalized the microbiota by fecal transplant and cage rotation, then split animals into control and exposed groups with arsenic provided in the water at 100 ppb. All mice received the same purified diet, and the facility kept temperature, humidity, and light cycles stable. Fecal samples were collected before exposure and after 13 weeks to compare diversity, composition, and metagenomic functions across time and treatment. Sequencing and downstream analyses defined taxonomic shifts and differential gene pathways linked to arsenic exposure.
Most important findings
Arsenic exposure reduced alpha diversity and separated beta-diversity profiles from controls over time. Firmicutes decreased while Verrucomicrobia increased, with notable genus-level losses in Lactococcus, Ruminococcus (Lachnospiraceae and Ruminococcaceae), Coprococcus, Dorea, Oscillospira, and unassigned Clostridiales. Akkermansia, Bifidobacterium, and Anaerostipes increased. Functionally, genes tied to pyruvate metabolism and SCFA synthesis (including acetate kinase and 3-hydroxybutyryl-CoA dehydrogenase) declined, suggesting reduced capacity to make butyrate and acetate that support epithelial energy and immune balance. In parallel, genes of the starch utilization system (susB, susC, susD, susR) rose, a likely compensatory shift in glycan harvesting. Arsenic enrichment of LPS biosynthesis, assembly, and transport genes pointed to a more pro-inflammatory bacterial output.
Oxidative stress and DNA repair modules (eg, superoxide dismutase, catalase, DnaJ, RecN) increased, consistent with a metal-induced stress milieu. Vitamin pathways expanded, including folate and B6, B12, thiamin, riboflavin, and menaquinone biosynthesis, a pattern that may reflect microbiome attempts to buffer redox stress and support methylation. Notably, classic arsenic resistance determinants (arsenate reductase and ACR3 efflux) decreased, while cobalt/zinc/cadmium resistance, multidrug efflux pumps, beta-lactamases, and many conjugative transposon proteins (Tra family) increased, signaling pressure toward horizontal gene transfer and antibiotic resistance traits under arsenic exposure. Together, these results define a signature of reduced SCFA potential, higher LPS capacity, and a stress-adapted, resistance-leaning gene repertoire at 100 ppb arsenic.
Key implications
For clinicians, this profile flags two actionable risks at low-dose exposure: weakened SCFA support for barrier function and immune tone, and amplified LPS-linked inflammatory signaling that can prime systemic effects. For microbiome databases, the directional taxa and pathway shifts provide a concise signature: loss of SCFA-producing Firmicutes lineages, gain of Akkermansia and Bifidobacterium, decline in pyruvate/SCFA genes, rise in Sus, LPS, stress, and vitamin modules, and enrichment of multidrug and conjugation genes. These signatures can guide exposure stratification in clinical cohorts, help interpret dysbiosis patterns in arsenic-exposed patients, and inform interventions that restore SCFA output while limiting pro-inflammatory load. The rise in resistance and horizontal gene transfer potential suggests environmental arsenic may co-select antibiotic resistance, an added concern for infection control.
Arsenic can disrupt both human health and microbial ecosystems. Its impact on the gut microbiome can lead to dysbiosis, which has been linked to increased disease susceptibility and antimicrobial resistance. Arsenic's ability to interfere with cellular processes, especially through its interaction with essential metals like phosphate and zinc, exacerbates these effects. By understanding how arsenic affects microbial communities and how these interactions contribute to disease, we can develop more effective interventions, including microbiome-targeted therapies and nutritional strategies, to mitigate its harmful effects.
Lipopolysaccharide (LPS), a potent endotoxin present in the outer membrane of Gram-negative bacteria that causes chronic immune responses associated with inflammation.