J Neurogastroenterol Motil  
Dysregulation of GABAergic Signalling Contributes in the Pathogenesis of Diarrhea-predominant Irritable Bowel syndrome
Surbhi Aggarwal,1 Vineet Ahuja,2 and Jaishree Paul1*
1School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; and 2Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
Correspondence to: Jaishree Paul, PhD
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
Tel: +91-11-26704156, Fax: +91-11-26742558, E-mail: jpaul33@hotmail.com
Received: August 28, 2017; Revised: January 22, 2018; Accepted: February 9, 2018; Published online: June 1, 2018.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
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.
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.
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.
Keywords: Cytokines; Gamma-aminobutyric acid; Irritable bowel syndrome; Inflammation; Lipopolysaccharides

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