Jörn-Hendrik Weitkamp, M.D., Pranathi Matta and colleagues are studying ways to identify necrotizing enterocolitis earlier. (photo by Joe Howell)
Premature babies, and particularly those who have early formula, are at increased risk for developing NEC. About 40 percent of babies with NEC require surgery to remove dead bowel tissue and half of these babies do not survive.
Jörn-Hendrik Weitkamp, M.D., a neonatologist and assistant professor of Pediatrics at Monroe Carell Jr. Children’s Hospital at Vanderbilt, and colleagues are reporting in the journal Gut that they have identified a new target for therapeutic interventions for NEC.
The team discovered that disruptions in immune system regulation — not previously considered to be important in NEC pathophysiology — may play a role in the disease, particularly in the “adaptive” immune response mediated by B cells and T cells.
This type of cellular immunity was not found in mouse models, Weitkamp said, but he knew from other studies that immune responses in newborn mice are not identical to immune responses in newborn humans.
The Vanderbilt researchers examined stored human intestinal tissue samples that had been surgically removed from preterm babies diagnosed with NEC or other intestinal diseases and found high levels of T cells (called T regulatory (Treg) cells) not found in the gut of newborn mice.
Treg cells suppress the immune response and are critical for keeping the immune system in balance, preventing harmful inflammation.
Because of limitations related to Treg cell detection in stored tissue samples, the investigators collected fresh intestinal tissue samples and found that babies with NEC had about 60 percent fewer Treg cells than babies with non-NEC problems.
“We believe that the T regulatory cells we’ve identified are in fact functional Treg cells and that they are down-regulated at the time of NEC,” Weitkamp said. “Our studies challenge the dogma that cellular immunity is not important in the immediate neonatal period or in the pathophysiology of NEC.”
Weitkamp and colleagues are now studying the intestinal microbiome — the collection of microbes colonizing the gut — in the surgically removed samples.
“We know that the microbiome and the immune system are important in shaping each other,” he said. “We need to understand exactly how that works and which components typically found in human milk — such as certain vitamins, prebiotics and probiotics — are important for healthy microbiome and healthy immune system development.”
Such components, he said, might become the basis for interventions to prevent the development of NEC.
The studies were supported by grants from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Vanderbilt’s National Institutes of Health-supported Clinical and Translational Science Award (CTSA) and Digestive Disease Research Center (DDRC).
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Monroe Carell Jr. Children’s Hospital at Vanderbilt