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

Abstract

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.

Gut Mucosal and Fecal Microbiota Profiling Combined to Intestinal Immune System in Neonates Affected by Intestinal Ischemic Injuries

“…The main ischemic and inflammatory diseases described in newborn are necrotizing enterocolitis (NEC), midgut volvulus, focal intestine perforation (Messaoudi et al, 2015;Chen et al, 2016;Wieck et al, 2016). Several published data suggest that in neonates affected by intestinal inflammatory injuries such as Necrotizing Enterocolitis (NEC), a reduced diversity and an altered gut microbiota composition may lead to a pro-inflammatory condition that may play a key role in their pathogenesis (Torrazza and Neu, 2013;Till et al, 2015;Moschopoulos et al, 2018). Despite specific bacteria have not been identified, recent papers have shown that some microbial signatures (e.g., Clostridium spp.…”

Necrotizing Enterocolitis, Gut Microbiota, and Brain Development: Role of the Brain-Gut Axis

“…The recognition of NEC-specific dysbiosis and/or the alteration of the microbiota may allow for a timely diagnosis, targeted treatment, and possibly even prevention or treatment of NEC. Furthermore, the inflammatory cascade induced by microbiota in NEC is considered not to be limited to the gut but may also influence the brain via the so-called bidirectional gut-brain axis [8]. …”

Necrotizing enterocolitis

“…The poor neurodevelopmental outcomes in infants with NEC may be secondary to a systemic inflammatory response and/or alterations in the gut‐brain axis . Neuronal degeneration in specific regions of the brain and blood‐cerebrospinal fluid barrier disruption occurs after induction of NEC in the preterm piglet model .…”

“…59,60 The poor neurodevelopmental outcomes in infants with NEC may be secondary to a systemic inflammatory response and/or alterations in the gut-brain axis. 7,61 Neuronal degeneration in specific regions of the brain and blood-cerebrospinal fluid barrier disruption occurs after induction of NEC in the preterm piglet model. 62 Using the same piglet model, genes associated with neuroinflammation were differentially expressed in the hippocampus following NEC induction, especially when injury is localized in the small intestine.…”