The Effects of an Environmentally Relevant Level of Arsenic on the Gut Microbiome and Its Functional Metagenome Original paper

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.