J Neurogastroenterol Motil.  2018 Jul;24(3):422-430. 10.5056/jnm17100.

Dysregulation of GABAergic Signalling Contributes in the Pathogenesis of Diarrhea-predominant Irritable Bowel Syndrome

• Aggarwal S
• Ahuja V
• Paul J

• KMID: 2417387
• DOI: http://doi.org/10.5056/jnm17100

Abstract

BACKGROUND/AIMS
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a prevalent functional bowel disorder. Abdominal pain, discomfort and altered intestinal habits are the salient features of IBS-D. Low grade inflammation and altered neurotransmitters are the 2 recently identified factors contributing to the pathogenesis of IBS-D, but their role and interactions has not been elucidated in detail. Here we investigate the potential role of γ-aminobutyric acid (GABA) in regulating gut inflammation during IBS-D.
METHODS
Blood samples and colonic mucosal biopsies from clinically diagnosed IBS-D patients and controls were collected. Levels of GABA were measured in serum samples through enzyme-linked immunosorbent assay (ELISA). Expression of GABAergic system and proinflammatory cytokines were analyzed in biopsy samples by reverse transcriptase polymerase chain reaction (RT-PCR). Effect of GABA and its antagonist on the expression of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated HT-29 cells was examined through RT-PCR.
RESULTS
ELISA data revealed diminished level of GABA in IBS-D patients as compared to controls. RT-PCR analysis showed altered GABAergic signal system in IBS-D patients as compared to controls. GABA reduced the expression of proinflammatory cytokines in LPS stimulated HT-29 cells, whereas bicuculline methiodide (GABA antagonist) upregulated the expression of same cytokines in LPS stimulated HT-29 cells.
CONCLUSIONS
Our sets of data indicate that diminished level of GABA and altered GABAergic signal system contributes to pathogenesis of IBS-D by regulating inflammatory processes. These results provide novel evidence for anti-inflammatory role of GABA in IBS-D patients by altering the expression of pro-inflammatory cytokines.

Keyword

Cytokines; Gamma-aminobutyric acid; Inflammation; Irritable bowel syndrome; Lipopolysaccharides

MeSH Terms

Abdominal Pain
Bicuculline
Biopsy
Colon
Cytokines
Enzyme-Linked Immunosorbent Assay
gamma-Aminobutyric Acid
HT29 Cells
Humans
Inflammation
Irritable Bowel Syndrome*
Lipopolysaccharides
Neurotransmitter Agents
Reverse Transcriptase Polymerase Chain Reaction
Bicuculline
Cytokines
Lipopolysaccharides
Neurotransmitter Agents
gamma-Aminobutyric Acid