The Gut‐Brain Axis in IBD: An Investigator’s Perspective

Three clinical observations in inflammatory bowel disease (IBD) prompt an examination of the role of gut‐brain interactions in the pathophysiology of IBD. The first is the recognition that anorexia is among several factors that lead to malnutrition in IBD patients. The second is the suspicion that stressful life events may precipitate exacerbations of IBD. The third is that IBD and irritable bowel syndrome (IBS) seem to be related. Recent work in animal models has provided insights into these clinical observations. Animal models of colitis exhibit a marked reduction in feeding during the acute phase of inflammation. Interestingly, thirst mechanisms are preserved and meal pattern analysis reveals that meal frequency is unchanged while meal size is reduced. These observations suggest that the anorexia does not reflect a general debility or malaise phenomenon. The anorexia is mediated in part by prostaglandins and interleukin‐10. In another set of experiments, the authors evaluated the effect of stress on colitis induced by trinitrobenzene (TNB) in rats. Mild restraint stress had no effect on the histology or activity of myeloperoxidase in rats that had not previously had colitis. In contrast, stress caused an acute exacerbation of colitis, reflected histologically and by myeloperoxidase activity, in rats with TNB colitis six weeks previously. These results provide new evidence in support of a causal relationship between stress and reactivation of intestinal inflammation. The apparent relationship between IBD and IBS has prompted speculation of a causal relationship between inflammation and gut ‘irritability’. Studies in animal models of colitis and jejunitis have shown that mucosal injury and inflammation are associated with neuromuscular dysfunction and abnormal motility. Neuromuscular dysfunction often persists after the mucosa has healed. More recent studies indicate that cells in the muscularis externa, which includes smooth muscle, are capable of cytokine and other inflammatory mediator production. Thus, one may speculate that the local production of mediators outlasts the mucosal injury and maintains a state of persistent dysfunction in the tissue. This may contribute to postinflammatory irritability in the gut. In summary, recent studies provide a tangible basis for further investigation of the inter‐relationships between behaviour and inflammation in the clinical expression of IBD.