Initiative aims to unlock gastrointestinal tract mysteries

Jan 15th, 2009 | By | Category: Issue, January 15, 2009, Research

The secrets to better human health may lie in the gut, and UNL expects to be on the leading edge of this emerging research.

UNL’s Gut Function Initiative has taken shape in the last year, with a team of about 12 scientists from across the university and some key new technology put in place. The initiative’s focus is to unlock the mysteries of the gastrointestinal tract and, ultimately, transform that understanding into practices and products  including what some call “designer foods” – that might help address obesity, disease and other concerns.

“Many of the most significant discoveries in human medicine are likely to occur in the GI ecosystem in the next 10 to 20 years,” said Andy Benson, food microbiologist and a member of the research team.

In fact, the National Institutes of Health, which help set the agenda of national medical research, has declared the study of gastrointestinal bacteria and probiotics a major research initiative. Probiotics are dietary supplements containing potentially beneficial bacteria.

Humans begin life with a sterile gastrointestinal tract, which comprises the small and large intestines. But microorganisms begin to take up residence during birth and rapidly thereafter – initially from mom and then from a variety of sources including environment and diet. Ultimately, the makeup of each person’s gastrointestinal microorganisms is as unique as fingerprints.

“Everybody’s got a different collection,” Benson said.

There are lots of them, to be sure – researchers estimate the GI tract has 10 times more microorganisms than cells in the entire human body, Benson said. It’s no wonder, then, that the composition of those microorganisms and what they do has eluded scientists for so long.

“This ecosystem is hellaciously complex,” said UNL gastrointestinal microbiologist Jens Walter, hired two years ago to be a part of the research team.

Daniel Peterson, a cellular immunologist, said, “Up until the last few years we couldn’t even tell what bacteria were living in the gut.”

Thanks to genomic advances, “we’re now demystifying this previously unmeasurable, incalculable population of bacteria,” added Peterson, who arrived at UNL in August to lead development of a new gnotobiotic facility that will be at the heart of UNL’s effort.

Gastrointestinal microorganisms have many useful functions: they help with digestion, stimulate cell growth, train the immune system, break down toxins and defend against some diseases.

Those are the “good guys” of the GI. There also are “bad guys,” which are believed to be linked to obesity, coronary disease, cancer, inflammatory bowel disease and other disease.

To put it simply, the idea is to find ways to encourage the beneficial bacteria and reduce the bad ones. UNL’s research will focus on three distinct areas:

– what microbial factors promote colonization of the GI tract;

– what host factors control bacterial development; and

– how dietary factors influence colonization.

The Institute of Agriculture and Natural Resources is particularly well-positioned to help answer these questions, Benson said, because it has the food-science expertise to study the GI tract and the production-agriculture expertise to put that knowledge to work.

“This is a new interface between agriculture and human health,” Benson said. “The newest ideas to emerge at this interface can be quickly integrated into the engines of agricultural production.

“For example, knowing how specific groups of the GI microorganisms contribute to health or disease will allow us to devise new dietary principles and nutrient strategies to encourage or inhibit” certain types of microorganisms, he added. “Understanding these key nutrients would have a profound effect on the development and breeding of new crops and ways of cultivating and processing them.”

The same principles could be applied to animal production, Benson said.

One key technology that will inform UNL’s research is the new gnotobiotic facility, a germ-free setting that will allow scientists to breed mice in a sterile environment and experiment with introducing certain, known bacteria into their GI tracts.

“We can bring in one bacteria, or two, at a time,” said Peterson, who will lead this research angle. If scientists know exactly what organisms are present, they can begin to figure out which ones do what.

UNL’s gnotobiotic facility is one of only about 10 in the country, Benson said.

Peterson, a medical doctor with a partial appointment at the University of Nebraska Medical Center, already can foresee exciting possibilities for collaboration with UNMC’s well-regarded gut-transplant program.

“There’s an immediate need, a great chance for application there,” Peterson said.

For example, many premature babies are born with immature GI tracts and this sometimes even results in loss of large amounts of the small intestine. UNL research could lead to vaccines, probiotics or nutritional supplements that would help these babies, Peterson said.

Obesity treatment in adults is another area of promise. Many people report weight gain after antibiotic therapy. Research could lead to development of a “cocktail of bacteria” that would be given to patients immediately after such therapy, which could stave off obesity, Benson said.

The marketing of probiotics has gotten ahead of the science, the UNL researchers say. Grocery-store shelves already are filled with pills, yogurt, smoothies, snack bars, cereals and other products that promise to regulate digestive health.

“There’s a snake-oil component to this,” Benson said. “As scientists we want to understand this and turn it into something realistic and rational that will really benefit consumers.

“This could keep us busy for the next 30, 40 years,” Walter added.

Although the Gut Function Initiative is relatively new, Benson said, it builds on years of previous work at IANR, including genetics research by animal scientist Merlyn Nielsen and cholesterol research by nutrition scientist Tim Carr.

The research will include UNL scientists with expertise in gastrointestinal microbiology, bioinformatics and statistics, immunology, allergy, metabolomics, quantitative genomics and physiology and nutrition. The Gut Function Initiative has received funding from the U.S. Department of Agriculture and the National Institutes of Health.

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