Fundamentals of Neurogastroenterology: Basic Science

Abstract

This review examines the fundamentals of neurogastroenterology that may underlie the pathophysiology of functional GI disorders (FGIDs). It was prepared by an invited committee of international experts and represents an abbreviated version of their consensus document that will be published in its entirety in the forthcoming book and online version entitled ROME IV. It emphasizes recent advances in our understanding of the enteric nervous system, sensory physiology underlying pain, and stress signaling pathways. There is also a focus on neuroimmmune signaling and intestinal barrier function, given the recent evidence implicating the microbiome, diet, and mucosal immune activation in FGIDs. Together, these advances provide a host of exciting new targets to identify and treat FGIDs and new areas for future research into their pathophysiology.

Keywords: enteric nervous system; mucosal barrier function; neuroimmune signaling; sensory physiology.

Conflict of interest statement

Conflicts of interest

The authors disclose no conflicts.

Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Mechanisms underlying sensitization. Luminal factors and mediators released in response to ischemia, injury, and inflammation act on the sensory endings to drive sensitization. These peripheral mechanisms are reinforced by central mechanisms in the spinal cord and CNS. ATP, adenosine triphosphate; LIF, leukemia inhibitory factor; NGF, nerve growth factor; PGE, prostaglandin E; TNF, tumor necrosis factor. Modified from Grundy and Brookes with permission from Morgan and Claypool.

Figure 2

Diagram showing inflammation-induced changes in the propulsive motor circuitry of the colon. Modified from Mawe with permission from Journal of Clinical Investigation.

Figure 3

Nerves express receptors for immune cell mediators. Immune mediators bind to receptors on nerves and can result in either excitation or inhibition of gut function. PAR, protease activated receptor; TNF, tumor necrosis factor; TRP, transient receptor potential; TTX-s, tetrodotoxin sensitive Na+ channels.

Figure 4

Intestinal barrier structure and function. Adapted with permission from Natividad et al. MAMP, microbe-associated molecular pattern; PRR, pattern recognition receptors.

Figure 5

Chronic psychological stress plays a significant role in the pathophysiology of IBS. CRF, corticotropin releasing factor. Reproduced from Barbara et al with permission from the Journal of Neurogastroenterology Motility.