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On the Hunt for Gut Microbe Troublemakers

Most people take their digestive system for granted. Few are aware of the link between some of the gut's natural microbial inhabitants and chronic disease.

Photo of Andrew Benson

Scientists have linked obesity, diabetes, some cancers and inflammatory bowel disease to some permanent residents in the gut. The challenge is to discover exactly which of the hundreds of species living in the gastrointestinal tract cause disease and under what conditions. Better understanding the role of gut microbes in disease could lead to new treatment options.

University of Nebraska-Lincoln food microbiologist Andrew Benson is on the hunt. He recently received a $997,732, two-year grant from the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases funded by the American Recovery and Reinvestment Act (ARRA) for this research. This project fits into the overarching goal of UNL's Gut Function Initiative, an interdisciplinary team that Benson helps lead, to understand the role of microorganisms in health.

To find the organisms responsible for disease, Benson first looks for specific genes in mice that cause the intestines of different animals to be colonized by different combinations of organisms. This is a difficult task because the composition of microbes in the gastrointestinal tract is a complex genetic trait controlled by the interactions of many genes.

By comparing the genes of individuals with different gut microbial populations, like comparing fast runners to slow runners, Benson can identify the different sets of genes that program different microbial compositions.

Next, he will look for overlaps between those genes and the genes associated with disease. The overlap will point back to the disease-inducing gut composition, and therefore the specific organisms. Although Benson is studying mice, the same microorganisms most likely have a similar effect in humans.

"Once you find the organisms, it gives you a different perspective on treating that disease," Benson said. "Rather than suppressing your immune system, for example, you can try to eliminate organisms that are problems."

Narrowing a complex genetic trait to specific genes, however, is difficult. Benson recruited Daniel Pomp, former UNL geneticist now at the University of North Carolina, to give the team the combined tools and expertise needed to do the job. Using a statistical genetic mapping technique, Pomp is comparing genes from mice strains that his team has bred to have different traits of microbial compositions.

"The mice are a very powerful set of genetic resources that we have access to," said Benson. "This really puts us on the map."

Mapping gut composition traits against an individual's genetic makeup is a unique approach and has received much interest from the NIH for its potential to lead to novel, more effective treatment options for diseases such as colitis, Crohn's and inflammatory bowel disease.

For Benson's team, ARRA funding provided an opportunity to move quickly into this exciting and promising new research area. He was able to retain three technicians and hire two others.

This article originally appeared on the University of Nebraska-Lincoln website. Reposted with permission.

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