What is the effect of inflammation on intestinal function?

Abstract

Chronic inflammatory bowel disease (IBD—Crohn’s disease [CD] and ulcerative colitis [UC]) are conditions characterized by widespread changes in bowel physiology, including abnormal secretion, motor dysfunction, and increased sensory perception. These changes contribute significantly to the generation of patient’s symptoms, such as abdominal pain and diarrhea.1,2 Attention has been recently paid to the impact of intestinal inflammation on the enteric nervous system (ENS), the major control mechanism of digestive functions. Nonetheless, it must be also acknowledged that changes in digestive functions in this context may be the consequence of the direct impact of inflammatory mediators on the target cells (e.g., epithelial and smooth muscle cells). Significant progress in our understanding of the mechanisms of altered bowel function in IBD has been achieved through the identification of the molecular basis of the interplay between bioactive substances released by inflammatory cells (e.g., cytokines, prostanoids, free radicals, etc.) and neural, muscular, epithelial, and endocrine cells controlling gastrointestinal function. Recent evidence shows that mild inflammation and subtle ENS abnormalities, including changes in nerve electrophysiology, chemical coding, and receptors expression (i.e., which have been referred to as neuronal plasticity) underlie substantial bowel dysfunction. These neuroplastic changes may play a role in bowel dysfunction detected at gastrointestinal sites not frankly involved by the inflammatory process or in sympathetic and parasympathetic branches of the autonomic nervous system residing outside of the gut wall.3 Based on these data, neuroplastic changes have been proposed to explain symptom perception also in patients with milder disease or during periods of remission of IBD. Animal models have provided important mechanistic insights into the pathophysiology of bowel dysfunction during intestinal inflammation. However, it must be noted that many of the morphological changes occurring at the level of the ENS and muscle described in IBD tissues cannot be reproduced in these experimental models. This is probably due to the fact that the chronic effect of inflammation present in human IBD determines changes that are difficult to be reproduced in the short course of inflammation in animals. In this brief review only general concepts and relevant examples of the impact of intestinal inflammation on the ENS and related functions will be discussed.