Grant: CIHR Fellowship

Chronic arsenic exposure affects over two billion individuals worldwide, and over 50 million people in Bangladesh alone. The U.S. Agency for Toxic Substances and Disease Registries has ranked arsenic as the top concern on the hazardous substance priority list, and the World Health Organization lists arsenic as among the top ten chemicals of most significant global health concern. Health Canada designates arsenic as a Class 1 (highest tier) substance assessed for carcinogenicity. The ramifications of chronic arsenic exposure on human health are severe, and include the development of bladder, lung, kidney and skin cancers; cardiovascular disease; and/or developmental delay. Arsenic poisoning-or, arsenicosis-results from contamination of water and soil due to both environmental and anthropogenic sources. Currently, there are no effective means to either prevent or treat arsenicosis, which therefore underscores the urgency to develop novel intervention and therapeutic strategies. The central hypothesis of the work herein is that the ingestion of arsenic alters the gut microbiota, and that such changes contribute to the development of arsenicosis. To test this hypothesis we propose a systems microbiota-based approach to 1) investigate the effects of arsenic on the composition and function of the microbiota; 2) determine how the microbiome affects the speciation and toxicity of arsenic; and 3) identify the mechanism(s) by which arsenic leads to individual differences in disease outcome. Our study employs metagenomics, biochemistry, microbial ecology and metabolomics, where the findings from such a multi-faceted approach will inform on arsenicosis risk assessment and prevention strategies, as well as developing treatment options for those with chronic arsenic exposure.