Two Montana State University researchers in different disciplines have teamed up to tackle the problem of arsenic poisoning, which is estimated by the World Health Organization to affect more than 100 million people worldwide, primarily through tainted drinking water.
"Just here in the U.S., something like 350,000 people are exposed to arsenic at levels that are above safe drinking standards that, because arsenic is a toxin, can lead to or increase the risk of certain cancers," said Seth Walk, assistant professor in the Department of Microbiology and Immunology in MSU's College of Agriculture and College of Letters and Science.
Walk is leading the five-year study with Tim McDermott, professor in MSU's Department of Land Resources and Environmental Sciences, to determine the role the human gut microbiome play in detoxifying arsenic after it has been ingested. Funding for the project comes from a $1.643 million grant from the National Cancer Institute and the National Institute of General Medical Sciences through its Institutional Development Award, or IDeA, program.
"We think we can impact the risk of cancer, maybe lower it, by understanding how microorganisms that live in the gastrointestinal tract metabolize arsenic," Walk said, adding that the study will leverage his expertise in the human gut microbiome and McDermott's expertise in microbe-arsenic interactions in the environment.
For the past couple of decades, McDermott's work has centered on remediating arsenic in the environment and understanding how a microbe senses and reacts to arsenic. He said he is looking forward to using the knowledge gained through his work and the work of his colleagues around the world to impact human health.
"It's satisfying to be able to transition from environmental settings -- be it hot springs in Yellowstone or arsenic-contaminated soils or well water -- into the biomedical arena," McDermott said.
Arsenic is a naturally occurring toxin that is released over time as rocks erode, and for more than 20 years it has held the top spot on the Environmental Protection Agency's list of the most dangerous toxins humans are exposed to, Walk said. Data from the U.S. Geological Survey suggests there are "hot spots" of arsenic in every state, some known and others not yet known.
"If you drink from a public water source, those sources are regulated," Walk said. "But if you drink from a private well, most people get their well tested once and then maybe never again, unless there's a reason to. It's important to raise awareness because of that."
Walk said that there is a significant problem with arsenic exposure in the western part of Gallatin County because of natural causes, such as thermal activity and the inherent geology of the area, rather than from manmade causes, such as mining.
But, McDermott added, whether arsenic is natural or from anthropogenic sources, it's still toxic.
"Once arsenic is in the environment, it is recycled by microorganisms and gets incorporated into the soil and plant material and into other things," Walk said. "It never really leaves, so it's a problem that isn't going to go away."
Recent studies in Walk's lab have shown that after arsenic is ingested, it can be metabolized by the microbiome in the gut, and that metabolism protects the host by letting the microorganisms "do their thing," Walk said.
"With this grant, we want to define what those mechanisms are, what metabolisms are good, and whether we can make them stronger," he said. "We're going to test hypotheses about whether the host and the host genes are important, and whether specific microorganisms that make up the human microbiome are important. Then, we can look into these microbes in more detail and determine what genes they carry."
Walk said that because of McDermott's previous work and that of others in the environmental microbiology field, the researchers already have an idea about what genes to look for, so they will use a multi-tiered approach based on both the host and microorganisms to see how each metabolizes arsenic.
"Microbes can transform a highly toxic molecule into one that is less toxic and that's what we want to do in the gut," Walk said. "We want to figure out which microbes are doing those metabolisms and how we can promote them to either excrete the arsenic and get it out of the gastrointestinal tract before it's taken up by host cells or transform it into less toxic substances."
This latest project grew from preliminary data McDermott and Walk gathered during a two-year exploratory grant from the National Institute of Environmental Health Sciences, or NIEHS. Their team, including Michael Coryell, Walk's doctoral student in MSU's Department of Microbiology and Immunology, made significant progress with this grant and will soon publish their findings.
"They (NIEHS) recognize the importance of the research, and they're very interested in microbiome research," McDermott said. "Many high-profile papers are coming out in respected journals illustrating how gut microbiome significantly influences the health and well-being of the host."
Walk and McDermott are also working with other MSU researchers with expertise in metabolism and toxicity. These include Brian Bother, professor and director of MSU's Mass Spectrometry Facility; Valerie Copié, professor and director of MSU's Nuclear Magnetic Resonance center; Debra Keil, associate professor of microbiology and immunology; and Ed Schmidt, professor of microbiology and immunology.
"This has been a great partnership," Walk said. "When I was hired here, the call was for systems biology. For this to happen, you need interdisciplinary research, which means you need people who can think across disciplines. The true intent of this approach is being fulfilled with this project."
Mark Jutila, head of MSU's Department of Microbiology and Immunology, said Walk's grant is particularly notable for a number of reasons.
"Dr. Walk has established a nationally recognized research program at MSU and provides unique expertise in the study of the function microorganisms in different compartments of the body and their impact on animal and human health," Jutila said. "This new grant award is particularly exciting since it represents culmination of a number of years of incredible collaborative efforts led by Dr. Walk, taking advantage of expertise across campus.
"Another exciting aspect of this project is the direct relevance to Montana, as well as its potential impact worldwide," he said.