The role of inflammation in irritable bowel syndrome (IBS)

Qin Xiang Ng,^1,2 Alex Yu Sen Soh,¹ Wayren Loke,² Donovan Yutong Lim,³ Wee-Song Yeo<sup>1

1</sup>National University Hospital, National University Health System, Singapore; ²MOH Holdings Pte Ltd, Singapore; ³Institute of Mental Health, Singapore

Abstract: Irritable bowel syndrome (IBS) is a complex, functional gastrointestinal ­disorder characterized by chronic abdominal pain or discomfort and altered bowel habits. Despite the global prevalence and disease burden of IBS, its underlying pathophysiology remains unclear. Inflammation may play a pathogenic role in IBS. Studies have highlighted the persistence of mucosal inflammation at the microscopic and molecular level in IBS, with increased recruitment of enteroendocrine cells. Substantial overlaps between IBS and inflammatory bowel disease have also been reported. This review thus aimed to discuss the body of evidence pertaining to the presence of mucosal inflammation in IBS, its putative role in the disease process of IBS, and its clinical relevance. Increased mast cell density and activity in the gut may correlate with symptoms of visceral hypersensitivity. As evidenced by patients who develop postinfectious IBS, infective gastroenteritis could cause systemic inflammation and altered microbiome diversity, which in turn perpetuates a cycle of chronic, low-grade, subclinical inflammation. Apart from mucosal inflammation, neuroinflammation is probably involved in the pathophysiology of IBS via the “gut–brain” axis, resulting in altered neuroendocrine pathways and glucocorticoid receptor genes. This gives rise to an overall proinflammatory phenotype and dysregulated hypothalamic–pituitary–adrenal axis and serotonergic (5-HT) functioning, which could, at least in part, account for the symptoms of IBS. Although a definite and reproducible pattern of immune response has yet to be recognized, further research into anti-inflammatories may be of clinical value.

Keywords: irritable bowel syndrome, postinfectious, inflammation, microbiome