Recent developments in the pathophysiology of irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.

Keywords: Diet; Endocrine cells; Genetic factors; Low-grade inflammation; Microbiota; Stem cells.

Figure 1

Chromogranin A-immunoreactive cells in (A) a healthy subject and (B) an irritable bowel syndrome patient.

Figure 2

The intestinal stem cell exerts 2 activities: clonogenic activity, where it produce a copy of itself to maintain the number of stem cells constant in the crypts, and differentiation activity. The differentiation consists of 2 lineages: secretory lineage and absorptive lineage. Through a cascade of progenitors the secretory lineage give rise to goblet, endocrine and Paneth cells and the absorptive lineage to absorptive enterocytes. In IBS patients, both clonogenic and differentiation activities are abnormal.

Figure 3

Msi-1-immunoreactive cells in duodenum of subjects from the (A) control, and (B) irritable bowel syndrome patient.

Figure 4

NEUROG3-immunoreactive cells in (A) a healthy subject and (B) an irritable bowel syndrome patient.

Figure 5

Schematic drawing to illustrate the possible pathophysiology of irritable bowel syndrome. Details are described in the text. IBS: Irritable bowel syndrome.