Arsenic is a naturally occurring toxic metalloid element to which prolonged exposure in humans is associated with keratosis, hyperpigmentation, lung and cardiovascular disease, and multiple forms of cancer. Chronically exposed individuals show high variability in symptoms, even among similarly exposed individuals. Host specific factors like genetic variability, body weight, and diet only partially account for this observed variability. In ecosystems where it occurs naturally, arsenic can exist in a variety of organic and inorganic chemical compounds of varying degrees of toxicity. In these environments, biochemical transformations of arsenic are primarily driven by microbial processes. Some microbes also have the ability to incorporate arsenic into their cellular biomass. The gastrointestinal tract (GIT) microbiome of mammals confers numerous important functional benefits to the host organism, many of which are not well understood or characterized. It has also been shown that altering gut microbial communities of mice can change the profile of arsenic transformations that take place in these communities. Preliminary research suggests that the GIT microbiome functions to protect the murine host from ingested arsenic. We have demonstrated that germ-free mice and mice with antibiotic-disrupted GIT microbiomes accumulate more arsenic in host tissues when compared with similarly exposed mice with conventional microbiomes. When the primary host system for detoxifying systemic arsenic is inactivated, mortality is observed in germ-free and antibiotic treated mice, even at low levels of arsenic exposure. The proposed research aims to investigate the function of the human microbiome in arsenic toxicity by leveraging the use of germ-free mice, which can be colonized with the GIT microbiome from a human donor. This research will investigate not only the influence of the human microbiome on host arsenic exposure, but also the mechanisms by which it influences. Arsenic transformations will be measured in germ-free and humanized mice while tracking host health to determine the health impacts of specific transformations in vivo. In order to determine if specific microbial groups increase or decrease the host's exposure to toxic arsenicals, the microbiome of humanized mice will be manipulated while monitoring arsenic transformations and host health. This research will elucidate new functions of the human microbiome relating to arsenic toxicity. There is potential for this project to have immediate impacts on human health interventions.

Public Health Relevance

There are many examples showing that the vast number microscopic organisms living inside of human the body can protect us from poisons and toxins that we are exposed to in our food and water. There is reason to believe that these beneficial germs are playing an important role in preventing people exposed to arsenic from getting sick. With this project we will ask which kinds of germs are the most beneficial to people who are exposed to arsenic and how we can take advantage of this information to inform public health decisions about arsenic and arsenic exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31ES026884-01
Application #
9124576
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Chadwick, Lisa
Project Start
2016-08-15
Project End
2019-08-14
Budget Start
2016-08-15
Budget End
2017-08-14
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Montana State University - Bozeman
Department
Microbiology/Immun/Virology
Type
Earth Sciences/Resources
DUNS #
625447982
City
Bozeman
State
MT
Country
United States
Zip Code
59717
Coryell, Michael; McAlpine, Mark; Pinkham, Nicholas V et al. (2018) The gut microbiome is required for full protection against acute arsenic toxicity in mouse models. Nat Commun 9:5424