Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA123

Poster Communications

Tuft cell hyperplasia in diarrhoea-predominant Irritable Bowel Syndrome colonic biopsies.

M. Connolly1, J. Aigbologa2, R. O'Brien1, M. Buckley2, J. Buckley3, D. O'Malley1,2

1. Physiology, University College Cork, Cork, Ireland. 2. APC Microbiome Institute, Cork, Ireland. 3. School of Medicine, University College Cork, Cork, Ireland.

Tuft cells are a rare subtype of gastrointestinal epithelial cell, which are thought to be activated by parasites and allergic reactions. Luminal stimulation causes release of pro-inflammatory cytokines, which can modulate gastrointestinal function. Irritable bowel syndrome (IBS), a heterogeneous functional bowel disorder, characterised by abdominal pain and altered bowel habit, exhibits altered circulating cytokine profiles. The aim of this study was to investigate if the number of colonic tuft cells was altered in human IBS or in a stress-sensitive animal model of IBS. The number of DCLKI immuno-labelled tuft cells with a strong cytoskeleton labelled with Phalloidin-iFluor 488 was compared between mucosal biopsies from diarrhoea- and constipation-predominant IBS patients and healthy controls (n=6 per group). The number of tuft cells was also compared in colonic cross-sections from stress-sensitive Wister Kyoto rats and the control Sprague Dawley comparators (n=3 per group). As compared to healthy controls, colonic tuft cell hyperplasia was detected in diarrhoea-predominant IBS mucosal biopsies (p<0.05). Increased numbers of tuft cells were also detected in the colonic mucosa of Wister Kyoto rats (p<0.05) as compared to Sprague Dawley controls. These findings illustrate a previously unreported change in IBS colonic morphology. Gastroenteritis, which could stimulate tuft cell hyperplasia, is a strong predictor of developing IBS. However, none of this patient cohort was diagnosed with post-infectious IBS. Moreover, clean rodent housing indicates that a catalyst other than the known stimuli of protozoans and helminths caused the increase in tuft cells in Wister Kyoto rats. Activation of the stress response and its capacity to exacerbate and prolong symptom flares is an accepted contributing factor in human IBS pathophysiology, and as such, is worthy of further investigation as an underlying cause of colonic tuft cell hyperplasia in IBS.

Where applicable, experiments conform with Society ethical requirements