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Evidence for Local and Systemic Immune Activation in Functional Dyspepsia and the Irritable Bowel Syndrome

A Systematic Review

B Biomed, Grace Burns, Sci (Hons)1,2,3; Carroll, Georgia, MBBS, G. Dip (S. Sc)2,3,4; Mathe, Andrea, PhD1,2,3; Horvat, Jay, PhD1,2; Foster, Paul, PhD1,2; Walker, Marjorie M., BMBS, FRCPA2,3,4; Talley, Nicholas J., MD, PhD, FRACP2,3,4; Keely, Simon, PhD1,2,3

American Journal of Gastroenterology: March 2019 - Volume 114 - Issue 3 - p 429–436
doi: 10.1038/s41395-018-0377-0

BACKGROUND: Subtle histopathologic features such as eosinophilia and increased mast cells have been observed in functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and the irritable bowel syndrome (IBS). The mechanisms that drive recruitment of these cells to the gastrointestinal tract remain unexplained, largely due to the heterogeneity in phenotypes among patients diagnosed with such conditions. We aimed to systematically review the literature and collate the evidence for immune activation in FD and IBS, and where possible, detail the nature of activation.

METHODS: Seven literature databases were searched using the keywords: ‘functional gastrointestinal disorder’, FGID, ‘functional dyspepsia’, ‘non-ulcer dyspepsia’, ‘idiopathic dyspepsia’, ‘irritable bowel syndrome’, IBS and ‘immun*’.

RESULTS: Fifty-one papers reporting discordant immune features met the selection criteria for this review. Changes in lymphocyte populations, including B and T lymphocyte numbers and activation status were reported in IBS and FD, in conjunction with duodenal eosinophilia in FD and increased colonic mast cells in IBS. Increases in circulating α4+β7+ gut-homing T cells appear to be linked to the pathophysiology of both FD and IBS. Studies in the area are complicated by poor phenotyping of patients into subgroups and the subtle nature of the immune activity involved in FD and IBS.

CONCLUSIONS: Alterations in proportions of gut-homing T lymphocytes in both FD and IBS indicate that a loss of mucosal homeostasis may drive the symptoms of FD and IBS. There is indirect evidence that Th17 responses may play a role in FGIDs, however the evidence for a Th2 immune phenotype in FD and IBS is limited. Although immune involvement is evident, large, well-characterised patient cohorts are required to elucidate the immune mechanisms driving the development of FGIDs.

1School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia;

2Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia;

3Priority Research Centre for Digestive Health and Neurogastroenterology, University of Newcastle, Newcastle, NSW, Australia;

4School of Medicine & Public Health, Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia.

Correspondence: Simon Keely, PhD. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received April 02, 2018

Accepted September 26, 2018

© The American College of Gastroenterology 2019. All Rights Reserved.
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