Colonic TRPV4 overexpression is related to constipation severity

Area of Science:

• Gastroenterology
• Microbiology
• Molecular Biology

Background:

• Chronic constipation is a prevalent condition linked to altered colon sensitivity and gut microbiota.
• Mucosa-associated microflora changes are implicated in constipation pathogenesis.
• Understanding the regulation of epithelial cell signaling in constipation is crucial.

Purpose of the Study:

• To investigate the regulatory mechanisms of Transient Receptor Potential Vanilloid 4 (TRPV4) expression by intestinal bacteria.
• To examine TRPV4 expression in colon epithelium of patients with chronic constipation.
• To explore the relationship between gut microbiota and TRPV4 in constipation.

Main Methods:

• Co-culture of colon epithelial cell lines with various enterobacteria, bacterial components, and metabolites.
• Assessment of TRPV4 expression and promoter DNA methylation using pyrosequencing and microarray analysis.
• Analysis of rectal TRPV4 expression and mucosa-associated microbiota in constipated patients.

Main Results:

• Co-culture with certain bacteria (K. oxytoca, E. faecalis, E. coli) increased TRPV4 expression in epithelial cells.
• E. coli supernatants elevated TRPV4 and TNF-alpha expression, modulated by butyrate and p38 signaling.
• Elevated TRPV4 expression was observed in constipated patients, correlating with clinical symptoms and E. faecalis frequency.

Conclusions:

• Colon epithelial TRPV4 expression is upregulated by specific bacterial supernatants and linked to TNFα signaling.
• Butyrate suppresses bacterial-induced TRPV4 upregulation.
• Increased epithelial TRPV4 expression and E. faecalis frequency may contribute to the pathogenesis of constipation.