BMC Med. 2022 Mar 31;20(1):115. doi: 10.1186/s12916-022-02301-8.

Grace L Burns ^1 2 3, Nicholas J Talley ^1 2 3, Simon Keely ^4 5 6

Author information

¹NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Callaghan, New South Wales, Australia.

²College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales, Australia.

³Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.

⁴NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Callaghan, New South Wales, Australia. simon.keely@newcastle.edu.au.

⁵College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales, Australia. simon.keely@newcastle.edu.au.

⁶Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia. simon.keely@newcastle.edu.au.

Abstract

Background: Irritable bowel syndrome (IBS) is considered a disorder of gut-brain interaction (DGBI), presenting as chronic abdominal pain and altered defaecation. Symptoms are often food related. Much work in the field has focused on identifying physiological, immune and microbial abnormalities in the colon of patients; however, evidence of small intestinal immune activation and microbial imbalance has been reported in small studies. The significance of such findings has been largely underappreciated despite a growing body of work implicating small intestinal homeostatic imbalance in the pathogenesis of DGBIs.

Main text: Small intestinal mechanosensation is a characteristic feature of IBS. Furthermore, altered small intestinal barrier functions have been demonstrated in IBS patients with the diarrhoea-predominant subtype. Small intestinal bacterial overgrowth and increased populations of small intestinal mast cells are frequently associated with IBS, implicating microbial imbalance and low-grade inflammation in the pathogenesis of IBS. Furthermore, reports of localised food hypersensitivity responses in IBS patients implicate the small intestine as the site of immune-microbial-food interactions.

Conclusions: Given the association of IBS symptoms with food intake in a large proportion of patients and the emerging evidence of immune activation in these patients, the current literature suggests the pathogenesis of IBS is not limited to the colon but rather may involve dysfunction of the entire intestinal tract. It remains unclear if regional variation in IBS pathology explains the various symptom phenotypes and further work should consider the intestinal tract as a whole to answer this question.