Vanderbilt University Medical Center has received a four-year, $2.23 million federal grant to determine whether a carbohydrate commonly found in human milk can protect the intestinal barrier from injury in adults.
The research, led by Fang Yan, MD, PhD, professor of Pediatrics, Medicine and Cell & Developmental Biology, may lead to new treatments for diseases such as inflammatory bowel disease (IBD) and mucositis, a severe complication of chemotherapy.
Epithelial cells lining the intestinal tract make up a “barrier,” a semipermeable mucosal structure that allows essential nutrients and immune molecules to be absorbed into the bloodstream, while preventing the entry of disease-causing molecules and bacteria.
IBD is a multigenic autoinflammatory disease that, along with other inflammatory disorders and cancer treatments, including chemotherapy and radiation therapy, can damage and disrupt the homeostasis (normal functioning) of the intestinal lining. Symptoms can include abdominal pain, diarrhea, bleeding, electrolyte imbalance, malnutrition, fatigue and severe infections.
Human milk contains carbohydrates called oligosaccharides that are beneficial, not only in helping infants grow, but in supporting intestinal health in adults. The most abundant oligosaccharide in human milk, 2’-fucosyllactose (2’-FL), is not found in dairy milk.
In previous studies, Yan and her colleagues found that 2’-FL can protect the intestinal barrier and help heal intestinal injury from colitis and mucositis in an adult mouse model.
The current study, funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, aims to establish the mechanism through which 2’-FL modulates the “community” of microorganisms that inhabit the human intestinal tract and how it directly protects intestinal tissues.
There is evidence that 2’-FL promotes the growth of beneficial bacteria and stimulates the transactivation of the epidermal growth factor receptor (EGFR) in intestinal epithelial cells.
Beneficial bacteria produce chemicals that protect the intestinal barrier. EGFR signaling stimulates cellular responses that can preserve the epithelial barrier and enhance regeneration of cells that have been damaged by disease or chemotherapy.
If successful, the research could help lay a foundation for developing human milk-derived oligosaccharides as a therapy for disorders of the intestinal barrier in adults, Yan said.
Yan’s colleagues includeSteven Townsend, PhD, John McLean, PhD, Stacy Sherrod, PhD, and Gabriela Codreanu, PhD (Department of Chemistry); Sari Acra, MD, PhD, Harpreet Kaur, PhD, Kasey Schalich, PhD, and Matthew Buendia, MD (Pediatrics); Richard Peek, MD and Yash Chotski, MD (Medicine); and M. Kay Washington, MD, PhD (Pathology, Microbiology and Immunology).
The research is supported by NIH grant R01DK136893.
