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

Area of Science:

• Gastroenterology
• Immunology
• Cell Biology

Background:

• Tuft cells are chemosensory cells in the gut epithelium that initiate immune responses.
• Irritable bowel syndrome (IBS) involves gut dysfunction, pain, and altered gut-brain communication.
• Immune dysregulation is implicated in IBS pathophysiology.

Purpose of the Study:

• To investigate changes in tuft cell density and interleukin-25 (IL-25) levels in patients with non-post-infectious IBS.
• To explore the role of tuft cells in IBS pathogenesis.

Main Methods:

• Immunofluorescent labeling of DCLK1-positive tuft cells in colonic biopsies from IBS subtypes and controls.
• Assessment of tuft cell numbers in animal models of IBS.
• Quantification of IL-25 in colonic biopsy secretions and plasma samples via immunoassay.

Main Results:

• Increased tuft cell density was observed in diarrhea-predominant IBS (IBS-D) but not constipation-predominant IBS (IBS-C) colonic biopsies.
• Elevated IL-25 concentrations were found in biopsy secretions and plasma of IBS-D participants.
• Tuft cell hyperplasia occurred in a rat IBS model, independent of helminth exposure or chronic stress.

Conclusions:

• Diarrhea-predominant IBS is associated with increased tuft cell density and IL-25 secretion.
• Tuft cell hyperplasia in IBS-D appears to be driven by factors other than helminth infection or chronic stress.
• These findings suggest a distinct innate immune pathway contributing to IBS-D pathogenesis.