Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies

Tuft cells are rare chemosensory sentinels found in the gut epithelium. When triggered by helminth infection, tuft cells secrete interleukin-25 (IL-25) basolaterally and subsequently evoke an immune response. Irritable bowel syndrome (IBS) is a common and heterogeneous disorder characterized by bowe...

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Main Authors: Jessica Aigbologa, Maeve Connolly, Julliette M. Buckley, Dervla O'Malley
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Psychiatry
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fpsyt.2020.00436/full
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author Jessica Aigbologa
Maeve Connolly
Julliette M. Buckley
Julliette M. Buckley
Dervla O'Malley
Dervla O'Malley
author_facet Jessica Aigbologa
Maeve Connolly
Julliette M. Buckley
Julliette M. Buckley
Dervla O'Malley
Dervla O'Malley
author_sort Jessica Aigbologa
collection DOAJ
description Tuft cells are rare chemosensory sentinels found in the gut epithelium. When triggered by helminth infection, tuft cells secrete interleukin-25 (IL-25) basolaterally and subsequently evoke an immune response. Irritable bowel syndrome (IBS) is a common and heterogeneous disorder characterized by bowel dysfunction and visceral pain sensitivity. Dysfunctional gut-brain communication and immune activation contribute to the pathophysiology of this disorder. The study aims were to investigate changes in tuft cell density in non-post-infectious IBS patients. Immunofluorescent labeling of DCLK1-positive tuft cells was carried out in mucosal biopsies from the distal colons of diarrhea and constipation-predominant IBS patients and healthy controls. Tuft cell numbers were also assessed in animal models. Concentrations of interleukin-25 (IL-25) secreted from colonic biopsies and in plasma samples were analyzed using an immunoassay. The density of tuft cells was increased in diarrhea—but not constipation-predominant IBS patient colonic biopsies. Biopsy secretions and plasma concentrations of IL-25 were elevated in diarrhea—but not constipation-predominant IBS participants. Tuft cell hyperplasia was detected in a rat model of IBS but not in mice exposed to chronic stress. Tuft cell hyperplasia is an innate immune response to helminth exposure. However, the patients with diarrhea-predominant IBS have not reported any incidents of enteric infection. Moreover, rats exhibiting IBS-like symptoms displayed increased tuft cell density but were not exposed to helminths. Our findings suggest that factors other than helminth exposure or chronic stress lead to tuft cell hyperplasia in IBS colonic biopsies.
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spelling doaj.art-444f684afb044880a2a69deb069bb2772022-12-21T21:17:07ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402020-05-011110.3389/fpsyt.2020.00436506693Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic BiopsiesJessica Aigbologa0Maeve Connolly1Julliette M. Buckley2Julliette M. Buckley3Dervla O'Malley4Dervla O'Malley5APC Microbiome Ireland, Cork, IrelandDepartment of Physiology, University College Cork, Cork, IrelandDepartment of Surgery, University College Cork, Cork, IrelandMater Private Hospital, Cork, IrelandAPC Microbiome Ireland, Cork, IrelandDepartment of Physiology, University College Cork, Cork, IrelandTuft cells are rare chemosensory sentinels found in the gut epithelium. When triggered by helminth infection, tuft cells secrete interleukin-25 (IL-25) basolaterally and subsequently evoke an immune response. Irritable bowel syndrome (IBS) is a common and heterogeneous disorder characterized by bowel dysfunction and visceral pain sensitivity. Dysfunctional gut-brain communication and immune activation contribute to the pathophysiology of this disorder. The study aims were to investigate changes in tuft cell density in non-post-infectious IBS patients. Immunofluorescent labeling of DCLK1-positive tuft cells was carried out in mucosal biopsies from the distal colons of diarrhea and constipation-predominant IBS patients and healthy controls. Tuft cell numbers were also assessed in animal models. Concentrations of interleukin-25 (IL-25) secreted from colonic biopsies and in plasma samples were analyzed using an immunoassay. The density of tuft cells was increased in diarrhea—but not constipation-predominant IBS patient colonic biopsies. Biopsy secretions and plasma concentrations of IL-25 were elevated in diarrhea—but not constipation-predominant IBS participants. Tuft cell hyperplasia was detected in a rat model of IBS but not in mice exposed to chronic stress. Tuft cell hyperplasia is an innate immune response to helminth exposure. However, the patients with diarrhea-predominant IBS have not reported any incidents of enteric infection. Moreover, rats exhibiting IBS-like symptoms displayed increased tuft cell density but were not exposed to helminths. Our findings suggest that factors other than helminth exposure or chronic stress lead to tuft cell hyperplasia in IBS colonic biopsies.https://www.frontiersin.org/article/10.3389/fpsyt.2020.00436/fullinterleukin-25irritable bowel syndromehelminthsWistar Kyotobrush cellsDoublecortin Linked Kinase-1
spellingShingle Jessica Aigbologa
Maeve Connolly
Julliette M. Buckley
Julliette M. Buckley
Dervla O'Malley
Dervla O'Malley
Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies
Frontiers in Psychiatry
interleukin-25
irritable bowel syndrome
helminths
Wistar Kyoto
brush cells
Doublecortin Linked Kinase-1
title Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies
title_full Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies
title_fullStr Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies
title_full_unstemmed Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies
title_short Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies
title_sort mucosal tuft cell density is increased in diarrhea predominant irritable bowel syndrome colonic biopsies
topic interleukin-25
irritable bowel syndrome
helminths
Wistar Kyoto
brush cells
Doublecortin Linked Kinase-1
url https://www.frontiersin.org/article/10.3389/fpsyt.2020.00436/full
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