Pathophysiology of Necrotizing Enterocolitis: An Update

NEC is a devastating disease that, once present, is very difficult to treat. In the absence of an etiologic treatment, preventive measures are required. Advances in decoding the pathophysiology of NEC are being made but a more comprehensive understanding is needed for the targeting of preventative strategies. A better definition of the disease as well as diagnostic criteria are needed to be able to specifically label a disease as NEC. Multiple environmental factors combined with host susceptibility appear to contribute to enhanced risks for developing this disease. Several different proximal pathways are involved, all leading to a common undesired outcome: Intestinal necrosis. The most common form of this disease appears to involve inflammatory pathways that are closely meshed with the intestinal microbiota, where a dysbiosis may result in dysregulated inflammation. The organisms present in the intestinal tract prior to the onset of NEC along with their diversity and functional capabilities are just beginning to be understood. Fulfillment of postulates that support causality for particular microorganisms is needed if bacteriotherapies are to be intelligently applied for the prevention of NEC. Identification of molecular effector pathways that propagate inflammation, understanding of, even incipient role of genetic predisposition and of miRNAs may help solve the puzzle of this disease and may bring the researchers closer to finding a treatment. Despite recent progress, multiple limitations of the current animal models, difficulties related to studies in humans, along with the lack of a "clear" definition will continue to make it a very challenging disease to decipher.