Serotonin, inflammation, and IBS: fitting the jigsaw together?

Abstract

Unexplained diarrhoea is a frequent indication for gastroenterologic referral, and after full investigation the most common final diagnosis is irritable bowel syndrome (IBS). Some patients with IBS describe an acute onset of symptoms following infective gastroenteritis. Postinfective IBS affects 7% to 31% of individuals infected, and appears to be a nonspecific response to injury which has been reported following Salmonella-, Campylobacter-, and Shigella-related IBS. The strongest risk factor for developing postinfective IBS is severity of the initial diarrhoea illness, but toxigenicity of the infected bacteria, age <60 years, and female sex also are important risk factors. Adverse life events, hypochondriasis, and depression are also important, as is increased enteroendocrine cell and lymphocyte numbers in rectal biopsies. Postinfective IBS and IBS with diarrhoea without an infectious onset both show increased postprandial release of serotonin, whilst constipated patients show a depressed release. Several studies suggest impairment of the serotonin transporter in IBS, which in animal studies has been shown to occur following a range of inflammatory insults. Clinical conditions with an inflammatory basis, such as coeliac and Crohn disease, also are characterised by excess postprandial serotonin release. Several studies report evidence of low-grade inflammation in IBS with diarrhoea. However, reliable markers of low-grade inflammation that may predict response to serotonin antagonists or other anti-inflammatory agents remain a goal for future research.