Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability, gut microbiota, psychosocial distress, gut inflammation, bile acids, food intolerance, colonic bacterial fermentation, and genetics. The molecular and cellular mechanisms of these factors are being actively investigated. In this mini-review, we present updates of these mechanisms and, where possible, relate the findings to childhood IBS. Mechanistic elucidation may lead to the identification of biomarkers as well as personalized childhood IBS therapies.

Keywords: Bile acid; Children; FODMAP; Genetics; Irritable bowel syndrome; Serotonin.

Fig. 1

The biopsychosocial model of irritable bowel syndrome. The circle represents the interrelated nature of the model. Several factors (in black bold) are present and affect other factors as shown by the direction of the red arrows. Mechanisms related to these factors are in blue font within the circle. The balance between pathogenic bacteria and commensal bacteria is in yellow. These factors ultimately come together and lead to IBS symptoms. Figure is modified from Rodriguez-Fandino et al. [10] and reproduced by permission of Journal of Neurogastroenterology and Motility

Fig. 2

Mast cell-nerve interactions in the human gut. Mast cells and nerves communicate bidirectionally, thereby modulating peristalsis and pain signaling. The release of bioactive, pro-inflammatory mediators by mast cells results in a variety of neuronal effects including activation, sensitization, and recruitment of nociceptors to the cell membrane, neurogenic inflammation, and neural sprouting. Ultimately, this leads to visceral hypersensitivity. Neuronal activation triggers the release of neuropeptides and neurotransmitters, thereby further activating mast cells. H1R = histamine-1 receptor; TRPV1 = transient receptor vanilloid 1; 5-HT3 = 5-hydroxytryptamine receptor; PAR2 = proteinase-activated receptor-2; TrkA = receptor for nerve growth factor; TLR = toll-like receptor; NK1 = neurokinin 1 receptor; SP = substance P; CGRP = calcitonin-related gene peptide; Ig = immunoglobulins; NGF = neuronal growth factor; PG = prostaglandins. Figure reproduced from “The role of mast cells in functional GI disorders,” Wouters et al. [41] with permission from BMJ Publishing Group Ltd.^© 2015 BMJ & British Society of Gastroenterology. All rights reserved