# Mechanisms of arsenic detoxification by the human microbiome

> **NIH NIH R01** · MONTANA STATE UNIVERSITY - BOZEMAN · 2024 · $374,699

## Abstract

Project Summary
 The proposed project addresses the role of the human microbiome in the detoxifying arsenic following
ingestion. Arsenic poisoning is a significant worldwide threat to public health that leads to a variety of human
diseases, including cancer. Polymorphisms in genes involved with arsenic metabolism and transport have been
epidemiologically linked to increased risk of lung, skin, bladder, and liver cancer, but there is large inter-individual
variability in cancers among similarly exposed individuals, indicating other important factors are involved in
disease penetrance. We showed the gut microbiome is an important determinant in arsenicosis and this project
continues to evaluate which microbiome-arsenic interactions provide the most benefits during exposure. This
includes engineering bacteria to evaluate specific microbiome-driven arsenical metabolisms in the gut of
gnotobiotic mice, focusing specifically on reduction, methylation, and thiolation pathways (Aim 1). We also found
antibiotic perturbation of the murine microbiome significantly increases the toxicity of inorganic arsenic and leads
to inter-individual differences in lethality. At least some of these differences appear to result from sepsis or
sepsis-like disease also observed in human arsenic poisoning. We will quantify the impact of commonly
prescribed antibiotics on arsenic toxicity and test whether microbiome manipulation can be used to rescue
arsenic-attributable sepsis (Aim 2). This information is important given the large number of individuals treated
with antibiotics in the US and countries around world. PD/PI's Walk and McDermott have had success leading
this multidisciplinary research program since 2017. The research new team members and collaborators with
years of training and technical expertise in murine models of the gut microbiome, microbial ecology, molecular
biology, arsenical speciation, clinical pharmacology, and immunology. Collectively, the assembled team will
ensure the continued success of a highly productive research effort into microbiome-arsenic-host interactions.

## Key facts

- **NIH application ID:** 10882697
- **Project number:** 2R01CA215784-06
- **Recipient organization:** MONTANA STATE UNIVERSITY - BOZEMAN
- **Principal Investigator:** Timothy McDermott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $374,699
- **Award type:** 2
- **Project period:** 2017-08-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882697

## Citation

> US National Institutes of Health, RePORTER application 10882697, Mechanisms of arsenic detoxification by the human microbiome (2R01CA215784-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10882697. Licensed CC0.

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