Parents of children with short bowel syndrome measure their outcomes by the centimeters of intestine that remain after surgery.
“A person needs a minimum of 35 centimeters to live a remotely decent life,” writes one mother. Her son has 41 centimeters.
Many of these children live on intravenous nutrients and fluids, in combination with formula via a gastric tube and a strict diet. All face daily challenges—infections, diarrhea and liver disease.
Through a collaborative project with clinical researchers and a microbiologist in Canada, assistant professor Crystal Levesque of the South Dakota State University Animal Science Department hopes to help find a treatment that will help grow their intestines. Beginning its second year, the project has been supported by an annual $25,000 Maurice Shils Grant from the Nestlé Nutrition Institute awarded through the American Society for Parenteral and Enteral Nutrition Rhoads Research Foundation.
Levesque, a pig nutritionist, did postdoctoral research at the University of Alberta in Edmonton and the University of Guelph in Ontario before coming to SDSU in January 2013. One undergraduate student is also working on the project.
Losing portions of intestines
Short bowel syndrome is rare, affecting only 25 out of every 100,000 live babies, according to fellow collaborator Dr. Paul Wales, a neonatal and pediatric surgeon at the Hospital for Sick Children in Toronto. However, the syndrome strikes 2.5 percent of premature babies, particularly those weighing less than 3.5 pounds. Wales has been instrumental in improving these children’s liver function through the Group for the Improvement of Intestinal Function and Treatment called GIFT.
More than a decade ago the mortality rate was as high as 37.5 percent in Canada, but that has improved to between 10 to 25 percent depending on the treatment center, reports collaborator Dr. Justine Turner, a pediatric gastroenterologist and nutrition researcher at Alberta Health Services.
Turner explained how in some preemies, the intestines are not fully formed or are twisted, while others have their intestines extruding outside their bodies through a hole in the belly button. Other infants experience a decrease in blood flow that causes the lining of the intestine to die, requiring surgical removal of these sections. That then affects their ability to absorb nutrients.
“Typically, these babies are on total parenteral nutrition,” Levesque explained, meaning they receive nutrients via an intravenous tube.
Stimulating bowel growth
“But the gut needs to be fed as well,” she added, noting that a healthy gut is often the first line of defense against infection. “We are trying different treatments that will help the remaining gut improve and grow, a bit wider and a little longer.”
From birth to adulthood, Turner pointed out the intestine doubles in length. The researchers want to understand the innate factors in normal bowel growth to identify growth factors that have the potential to help these babies.
The team is testing two types of treatments for infants--alone and in combination. The first, glucagon-like peptide 2, or GLP-2, is given intravenously, but is approved only for adults. The second treatment is modified bacteria that secrete a natural growth factor found in milk called epidermal growth factor, or EGF, developed at the lab of collaborator Julang Li, a professor of animal and poultry science at University of Guelph.
Levesque and her associates hope that, taken orally, the EGF will stimulate growth in the gut. The researchers seek to improve the gut by feeding it from both sides—intravenously and orally.
In addition, the EGF-secreting bacteria do not colonize the already-compromised intestinal tract, Levesque explained. That’s important, she noted because “the small intestine is sensitive to overgrowth of the bacterial population. In the short term, the modified bacteria secrete EGF to help build the gut, but when feeding stops, the bacteria are excreted.”
The goal is to improve the function of the gut so these babies can tolerate increasing amounts of oral fluids, but the results may vary based on what portions of the intestinal tract remain.
Identifying factors lost
The one-way ileocecal valve at the junction between the small and large intestines prevents the contents of the lower tract from moving back up the small intestine. Often this has to be removed along with the adjacent section of the small intestine called the ileum, Levesque explained, “so they lose that regulatory mechanism.”
Turner pointed out that this is “the exact part we have shown is most needed for normal bowel growth.” Through the use of a pig model, Levesque can help the clinical researchers understand what growth factors are lost when this portion of the bowel is removed and how these hormones can be replaced.
Her work focuses on determining how the gut microbes change when sections of the small intestine are removed with and without the ileocecal valve. She will also look at the effect that treatments, such as EGF, have on intestinal growth. The last of the animal trials will be completed in May.
“By understanding the change in microbial population, we can develop probiotics that interact with those bacteria to improve the population, stimulate further growth and restore the proper barrier function,” Levesque said.
Though researchers are optimistic about GLP-2’s potential for helping babies, but Turner cautioned, “it is not likely to be an answer on its own.”
Through this collaborative project, Turner noted, “We are finding some combinations that show particular promise.”
These treatments can bring a better quality of life to children with short bowel syndrome and to the families who care for them.
About South Dakota State University
Founded in 1881, South Dakota State University is the state’s Morrill Act land-grant institution as well as its largest, most comprehensive school of higher education. SDSU confers degrees from eight different colleges representing more than 175 majors, minors and specializations. The institution also offers 29 master’s degree programs, 13 Ph.D. and two professional programs.
The work of the university is carried out on a residential campus in Brookings, at sites in Sioux Falls, Pierre and Rapid City, and through Cooperative Extension offices and Agricultural Experiment Station research sites across the state.