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Mediators of Inflammation
Volume 2018, Article ID 7456857, 8 pages
Review Article

The Neurodevelopmental Perspective of Surgical Necrotizing Enterocolitis: The Role of the Gut-Brain Axis

1Department of Pediatrics, Flushing Hospital Medical Center, SUNY-Stonybrook School of Medicine, Flushing, NY, USA
2Division of Neonatology and Center for Research in Neuroscience, Children’s National Medical Center, George Washington University School of Medicine, Washington, DC, USA
3Department of Emergency Medicine, Children’s National Medical Center, George Washington University School of Medicine, Washington, DC, USA
4Division of Pediatric Surgery, Palmetto Health Children’s Hospital, University of South Carolina School of Medicine, Columbia, SC, USA
5St. Christopher’s Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, USA

Correspondence should be addressed to Panagiotis Kratimenos; gro.lanoitansnerdlihc@sonemitark.sitoiganap

Received 3 September 2017; Revised 22 January 2018; Accepted 5 February 2018; Published 11 March 2018

Academic Editor: Mirella Giovarelli

Copyright © 2018 Chariton Moschopoulos et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


This state-of-the-art review article aims to highlight the most recent evidence about the therapeutic options of surgical necrotizing enterocolitis, focusing on the molecular basis of the gut-brain axis in relevance to the neurodevelopmental outcomes of primary peritoneal drainage and primary laparotomy. Current evidence favors primary laparotomy over primary peritoneal drainage as regards neurodevelopment in the surgical treatment of necrotizing enterocolitis. The added exposure to inhalational anesthesia in infants undergoing primary laparotomy is an additional confounding variable but requires further study. The concept of the gut-brain axis suggests that bowel injury initiates systemic inflammation potentially affecting the developing central nervous system. Signals about microbes in the gut are transduced to the brain and the limbic system via the enteric nervous system, autonomic nervous system, and hypothalamic-pituitary axis. Preterm infants with necrotizing enterocolitis have significant differences in the diversity of the microbiome compared with preterm controls. The gut bacterial flora changes remarkably prior to the onset of necrotizing enterocolitis with a predominance of pathogenic organisms. The type of initial surgical approach correlates with the length of functional gut and microbiome equilibrium influencing brain development and function through the gut-brain axis. Existing data favor patients who were treated with primary laparotomy over those who underwent primary peritoneal drainage in terms of neurodevelopmental outcomes. We propose that this is due to the sustained injurious effect of the remaining diseased and necrotic bowel on the developing newborn brain, in patients treated with primary peritoneal drainage, through the gut-brain axis and probably not due to the procedure itself.