Joanna Cosgrove03.01.09
Unlocking the Mysteries of the GI Tract
UNL researchers embark on a long-term mission to improve overall health by unraveling the nuances of the gut.
By Joanna Cosgrove
Online Editor
Daniel Peterson, UNL assistant professor food science and technology, and member of the research team, commented that today’s advanced technologies underscored the timing of this endeavor. “The technology for DNA sequencing has made it possible to study organisms that cannot be measured in test tubes and Petri dishes,” he said. “We know not only what genes a bacteria that lives in the gastrointestinal tract have, but also which ones are expressed in different situations. So now we start to ask the fundamental questions like: what bacteria does the body choose to respond to out of the 1000 different species that live there, and what does that response do to the bacteria, and does that conversation between the microbe and the body impact disease and health?”
The GI ecosystem’s relation to human health is such a crucial area of focus that the National Institutes of Health deemed the study of GI bacteria and probiotics a “major research initiative” and help set the agenda of national medical research.
According to an article published in Scarlet, UNL’s newspaper, the microorganism makeup of the human GI tract is as individualized as a fingerprint. 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.
The GI system is comprised of a complex blend of “good” and “bad” microorganisms that help with digestion, stimulate cell growth, train the immune system, break down toxins and defend against some diseases. But this blend of bacteria also can contribute to conditions such as obesity, heart disease, cancer, inflammatory bowel disease, and many others.
Researchers estimate the GI tract has 10 times more microorganisms than cells in the entire human body—no doubt, that’s why the composition of those microorganisms and what they do has eluded scientists for so long.
According to the Scarlet, this research endeavors to uncover ways to encourage beneficial bacteria and reduce bad bacteria. It will focus on three core areas: the microbial factors responsible for promoting the colonization of the GI tract; the host factors controlling bacterial development; and how dietary factors influence colonization. The research will include UNL scientists with expertise in gastrointestinal microbiology, bioinformatics and statistics, immunology, allergy, metabolomics, quantitative genomics and physiology and nutrition.
Dr. Andy Benson, food microbiologist and research team member told the Scarlet, “Knowing how specific groups of 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 said. “Understanding these key nutrients would have a profound effect on the development and breeding of new crops and ways of cultivating and processing them.”
Dr. Peterson will lead the team’s development of a new gnotobiotic facility (one of only 10 in the country), which will be at the heart of UNL’s research effort. The gnotobiotic facility is 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 grow mice that are sterile or free of all bacteria and then use them like a living test tube by inoculating them with a single microbial species, or defined microbial community…unlike a glass test tube, the mouse gut is a dynamic vessel that moves, responds and provides a real gut environment to model what is happening in the human gut,” he explained.
The applications for this knowledge are both far-reaching and immediate, especially as it pertains to the possibility of collaboration with the University of Nebraska Medical Center’s well-regarded gut-transplant program, where, in the case of premature babies born with immature GI tracts, there can be large amounts of small intestine loss. This research could lead to the creation of vaccines, probiotics or nutritional supplements that could help these babies.
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.
“If we learn what causes the abnormal immune responses that we see in colitis and food allergies in the gut, or even the impact of gut microbes on the systemic immune system like rheumatoid arthritis and juvenile diabetes, then we can use things like pre-and probiotics to impact specific changes in gut microbiota to treat or prevent these diseases,” said Dr. Peterson.
As it relates to functional foods and supplements, the team told the Scarlet that the marketing of probiotic pills, yogurts and other snacks to regulate digestive health has gotten ahead of the science. “There’s a snake-oil component to this,” Dr. Benson said. “As scientists we want to understand this and turn it into something realistic and rational that will really benefit consumers.”
The probiotic arm of the research will be helmed by Professor Bob Hutkins, who will work with Dr. Peterson to introduce the probiotics into the gnotobiotic mouse model. “Probiotics are almost paradoxical for gut microbial ecology…[it is] difficult to study the complex nutritional and biochemical web between 500-1000 different bacterial types,” said Dr. Peterson. “Because of the tools and models that are available to us here within the Gut Function Initiative, we can look at the impact of probiotics on both the host and the microbial ecology of the gut, and start to understand the mechanisms by which these probiotics work.”
Another aspect of the research will delve into the opportunities afforded by so-called designer foods. “The picture is emerging that there are changes in the gut microbial community that are associated with specific diseases like obesity. A designer food might be one that is designed to promote the microbes associated with ‘leanness’ and inhibit those that are associated with obesity (a prebiotic type of approach),” said Dr. Peterson. “Whether or not we can someday administer good microbial communities to patients will have to be decided by well-designed research. In many areas the key is not finding good ideas, but finding the models and analytical tools that allow you to test these ideas in a controlled experiment. That is the essence of what we are building here at UNL, a model system and analytical tools that will allow us to prove that a designer food, probiotic, prebiotic or other treatments have clear impacts in a controlled mouse experiment.”
The Scarlet reported that the Gut Function Initiative’s research team could likely span 30-40 years. While the Gut Function Initiative is relatively new, it builds on years of previous work at the UNL’s Institute for Agriculture and Natural Resources (IANR), including genetics research by animal scientist Merlyn Nielsen and cholesterol research by nutrition scientist Tim Carr. The Gut Function Initiative has received funding from the US Department of Agriculture (USDA) and the National Institutes of Health (NIH).
“This is not a short-term research project, but a long-term commitment to understanding the gut immune system in both health and disease,” commented Dr. Peterson.