The National Institute of Allergy and Infectious Diseases of the National Institutes of Health will grant $433,340 for two years to the lab of Xiaolei Tang, PhD, professor at Loma Linda University School of Medicine, to pursue the research project titled “Targeting Intestinal Stem Cells to Augment the Repair of Epithelial Barrier.”
“I am very excited that our idea is supported by the experts in our field,” Tang said in a university feature story by Ansel Oliver. “I hope that this study will eventually benefit patients at Loma Linda University Health and around the world.”
IBD is triggered by an inappropriate immune response towards gut bacterial flora, or bacterial microbiota. Normally, the digestive tract harbours a complex community of different bacteria that help defend the body from infections, develop the immune system, and make the intestines able to digest food. Recent research also suggests that these bacteria can send signals to the brain.
In IBD, the immune system mistakes the body’s own microbes, food, and other materials for foreign bodies, and attacks the intestine. Gut bacteria are normally contained outside the intestinal wall. However, in people with IBD, the excessive gut inflammation ends up damaging the intestinal wall, allowing the bacteria to sneak in.
As bacteria reach internal organs, IBD worsens, which in turn allows more bacteria to pass through the gut wall. Unless the wall is repaired, this harmful cycle continues.
No medications are currently available to overcome this particular problem. However, recent studies suggest that vitamin D may be helpful.
Vitamin D is key for the normal functioning of intestinal stem cells (ISCs), which are responsible for renewing the gut wall every five to seven days, ensuring its integrity. Tang and his team hypothesized that such renewal capacity can be exploited to repair the injured intestinal wall in IBD patients.
They will first determine if vitamin D delivered to the intestine promotes ISCs’ capacity for regenerating the intestinal wall, or epithelium, both in healthy mice and in a mouse model of colitis. They will also explore the ways in which, on a molecular scale, vitamin D can enhance the regenerative function of ISCs.
The project intends to provide evidence on whether boosting intestinal epithelial repair can be a novel therapeutic strategy for IBD.
Current IBD medications, which block intestinal immune responses, are able to reduce disease severity, delay disease progression, and improve quality of life but frequently patients “do not go into remission, suggesting that novel therapeutic strategies targeting different mechanisms are needed,” the researchers wrote in their grant summary.
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