# Microbial Contributions to Arsenic Transformation in the Gut

> **NIH NIH P42** · UNIVERSITY OF ARIZONA · 2022 · $287,557

## Abstract

ABSTRACT (Project 3: Pawel Kiela, Paul Carini, and Albert Barberán) 
Legacy mine tailings that remain after extraction of economic metals are frequently enriched with co-occurring 
contaminants such as arsenic (As) that pose serious health hazards to neighboring communities and 
ecosystems. As-ingestion has been associated with diabetes, numerous cancers, and cardiovascular 
disorders. The mode of action for As toxicity is not clear; however, the degree of toxicity is associated with the 
valence and the methylation state of As metabolites (e.g. trivalent As species, iAsIII, MMAIII, and DMAIII ,are two 
times more cytotoxic than iAsV; methylated pentavalent arsenicals are 10-fold less cytotoxic than AsV). The gut 
microbiome is a primary point of contact for As in the host because oral ingestion is the principal exposure 
route. In addition, in vitro studies have demonstrated the capacity of human colon microbiota to biotransform 
iAs to both more and less toxic forms. Thus, accurate As risk assessment requires understanding of 
presystemic contributions by the gut microbiome to the bioaccessibility and speciation of the host As-load. The 
overall objectives of this proposal are to 1) contextualize the composition of the mouse gut 
microbiome with its functional capacity to metabolize As and to 2) evaluate the capacity of defined As- 
transforming microbial communities to affect in vivo diabetic outcomes following As exposure. The 
multidisciplinary team will employ a unique approach to identify specific associations between the composition 
of the gut microbiome, its genetic and functional capacity to sequester and/or transform As, and its capacity to 
either exacerbate or mitigate host diabetic outcomes in response to As exposure. Routine microbial taxonomic 
(16S rRNA gene amplicon profiling) and functional gene (shotgun metagenome) analyses will identify the 
impact of host sex, age and As-exposure on mouse fecal community composition. This molecular analysis will 
be combined with function-based high throughput culture analysis of the same fecal communities to facilitate 
the design of 120 distinct synthetic microbial communities (SynComs). The functional capacities of each 
SynCom to transform/sequester iAs will be identified and will potentially capture emergent properties of 
microbially-mediated As biotransformation that might be missed in studies using isolated phylotypes. The 
SynComs will be clustered in functional guilds with differing capacities to increase or decrease the As-load 
experienced by the host. These SynComs will be tested in germ-free mice to evaluate the capacity of specific 
microbial consortia with distinct As biotransformation capacities to modulate diabetic outcomes of As exposure. 
It is hypothesized that microbial communities that reduce As toxicity and associated diabetic outcomes can be 
exploited as potential probiotics. This hypothesis will be tested through verification of the ability of positive- 
outcome S...

## Key facts

- **NIH application ID:** 10337262
- **Project number:** 5P42ES004940-33
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Pawel R Kiela
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $287,557
- **Award type:** 5
- **Project period:** 1997-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337262

## Citation

> US National Institutes of Health, RePORTER application 10337262, Microbial Contributions to Arsenic Transformation in the Gut (5P42ES004940-33). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10337262. Licensed CC0.

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