Glioplasticity in irritable bowel syndrome

Abstract

Background

Growing evidence indicates a wide array of cellular remodeling in the mucosal microenvironment during irritable bowel syndrome (IBS), which possibly contributes to pathophysiology and symptom generation. Here, we investigated whether enteric glial cells (EGC) may be altered, and which factors/mechanisms lead to these changes.

Methods

Colonic mucosal biopsies of IBS patients (13 IBS-Constipation [IBS-C]; 10 IBS-Diarrhea [IBS-D]; 11 IBS-Mixed [IBS-M]) and 24 healthy controls (HC) were analyzed. Expression of S100β and GFAP was measured. Cultured rat EGC were incubated with supernatants from mucosal biopsies, then proliferation and Ca²⁺ response to ATP were analyzed using flow cytometry and Ca²⁺ imaging. Histamine and histamine 1-receptor (H1R) involvement in the effects of supernatant upon EGC was analyzed.

Key Results

Compared to HC, the mucosal area immunoreactive for S100β was significantly reduced in biopsies of IBS patients, independently of the IBS subtype. IBS-C supernatants reduced EGC proliferation and IBS-D and IBS-M supernatants reduced Ca²⁺ response to ATP in EGC. EGC expressed H1R and the effects of supernatant upon Ca²⁺ response to ATP in EGC were blocked by pyrilamine and reproduced by histamine via H1R. IBS supernatants reduced mRNA expression of connexin-43. The S100β-stained area was negatively correlated with the frequency and intensity of pain and bloating.

Conclusion and Inferences

Changes in EGC occur in IBS, involving mucosal soluble factors. Histamine, via activation of H1R-dependent pathways, partly mediates altered Ca²⁺ response to ATP in EGC. These changes may contribute to the pathophysiology and the perception of pain and bloating in patients with IBS.

This study aimed to determine whether changes in enteric glial cells occur in irritable bowel syndrome (IBS), by studying colonic biopsies from patients and controls. Expression of the glial marker S100β was decreased in the colonic mucosa of IBS patients. In vitro exposure of cultured rat enteric glial cells to mucosal biopsies supernatant of IBS patients decreased their proliferation and inhibited their ATP-induced Ca2+ response, via a histamine-dependent pathway.

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