Necrotizing enterocolitisÂ (NEC) is a major cause of injury and death in premature newborns, affecting nearly 10% of infants born prematurely or with low birth weight. In spite of numerous studies over the years, it has been difficult to track down a single unifying cause for this disease. Last year, however,Â Dr. Akhil Maheshwari, physician and researcher at the University of Illinois Chicago College of Medicine, made a discovery that has exciting potential applications in the early diagnosis and treatment of this disease.
During NEC, bacteria in theÂ baby’s intestine trigger a strong inflammatory response causingÂ tissue damage. ThisÂ is somewhat surprising when you consider that, as adults, each of usÂ normally carriesÂ trillions of bacteria in our large intestines, all of which stayÂ in perfect harmony withÂ the hostÂ in a mutually beneficial relationship.
Maheshwari and his colleagues wondered how this could be possible.Â He postulatedÂ that (1) the mature intestine must have developed ways to adapt to the huge load of immunostimulatory bacteria in the gut lumen, minimizingÂ adverse inflammatory responsesÂ to these bacteria and their products,Â and (2) these mechanisms for the normal suppression of inflammationÂ are not yet in place in the premature intestine.
This line of reasoning could go a long way toward explaining why NEC is associated with several, diverse causes of gut injury, seemingly lacking any common thread.Â Instead we can now envision it, not as single disease entity, but as aÂ generic response of the developing intestinal tissue to diverse forms of injury.
This new theory led Dr Maheshwari and colleagues to examine the differences between the premature and the adult intestine.Â What they discovered is that the developing intestine lacks a protein, calledÂ transforming growth factor-beta 2, that trains the host defense mechanisms in the intestine to minimize the inflammatory responses while still maintaining mechanisms for eliminating wayward bacteria.
This discoveryÂ raises exciting possibilities both for early diagnosis of NEC and forÂ developingÂ novel ways to treat this disease.
In the 2012Â Joseph V. Scaletti Memorial Catalyst Lecture, Dr Maheshwari focuses on unique aspects of inflammation in the premature intestine and outlines potential mechanisms for correcting areas of imbalance for both preventative and therapeutic purposes.