Targeting γ-aminobutyric acid pathways in irritable bowel syndrome - bridging central nervous system, enteric dysfunction, and the microbiota-gut-brain axis

Sep 29, 2026

Uploaded by Mabel

Irritable bowel syndrome (IBS) is a complex disorder within the gut-brain interaction framework. Emerging evidence links γ-aminobutyric acid (GABA) biology to IBS symptom development, since the GABAergic system can regulate visceral pain, intestinal motility, epithelial barrier integrity, and immune signaling. GABA receptors and transporters act across the central nervous system, enteric nervous system, and gut epithelium, while gut microbiota can produce GABA. This review discusses GABAergic dysregulation in IBS pathogenesis and summarizes preclinical and limited clinical therapeutic strategies targeting the GABAergic system, highlighting the need for randomized trials.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

IBS as a gut-brain interaction disorder

Evidence linking GABA to IBS symptoms

GABAergic regulation across multiple levels

Central nervous system circuits

Enteric dysfunction and gut epithelium

Microbiota-gut-brain axis

Therapeutic implications targeting the GABAergic system

GABA receptor modulators

Dietary supplements and probiotics

TYPE Review PUBLISHED 22 December 2025 DOI 10.3389/fphar.2025.1677037 OPEN ACCESS EDITED BY Ludovico Abenavoli, Magna Græcia University, Italy REVIEWED BY Yiming Meng, China Medical University, China Gitanjali Deokar, Bhujbal Knowledge City, India Chuda Chittasupho, Chiang Mai University, Thailand *CORRESPONDENCE Christian Lambiase, [christian.lambiase@phd.unipi.it](christian.lambiase@phd.unipi.it) RECEIVED 31 July 2025 REVISED 17 November 2025 ACCEPTED 02 December 2025 PUBLISHED 22 December 2025 CITATION Lambiase C, Rettura F, Sciumè GD, Tedeschi R, Grosso A, Cancelli L, Bottari A, Fornai M, Antonioli L, de Bortoli N and Bellini M (2025) Targeting γ-aminobutyric acid pathways in irritable bowel syndrome: bridging central nervous system, enteric dysfunction, and the microbiota-gut-brain axis. Front. Pharmacol. 16:1677037 . doi: 10.3389/fphar.2025.1677037 COPYRIGHT © 2025 Lambiase, Rettura, Sciumè, Tedeschi, Grosso, Cancelli, Bottari, Fornai, Antonioli, de Bortoli and Bellini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Targeting γ -aminobutyric acid pathways in irritable bowel syndrome: bridging central nervous system, enteric dysfunction, and the microbiota-gut-brain axis Christian Lambiase 1,2*, Francesco Rettura 1,2,3, Giusi Desirè Sciumè 1,2, Riccardo Tedeschi 1,2, Antonio Grosso 1,2, Lorenzo Cancelli 1,2, Andrea Bottari 1,2, Matteo Fornai 4, Luca Antonioli 4, Nicola de Bortoli 1,2 and Massimo Bellini 1,2 1Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy, 2Regional Center for Functional and Motility Digestive Disorders, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy, 3Gastroenterology Unit, Annunziata Hospital, AOCS, Cosenza, Italy, 4Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Irritable bowel syndrome (IBS) is a complex and multifaceted disorder of the gutbrain interaction. Recent evidence suggests that γ-aminobutyric acid (GABA) maybe involved in the development of IBS symptoms. Indeed, the GABAergic system exerts many gastrointestinal functions, such as modulation of visceral pain, intestinal motility, intestinal barrier integrity and immune response. GABA receptors and transporters are present and may inﬂuence intestinal functions at multiple levels: in the central nervous system, in the enteric nervous system and at the gut epithelial level. Furthermore, the gut microbiota is capable of producing GABA. This may also suggest a direct link between. intestinal microbiota composition and GABAergic tone within the microbiota gut-brain axis. Conﬁrming the involvement of GABAergic dysregulation in IBS, altered GABA signaling and reduced GABA levels have been observed in this disease, especially in diarrhea-predominant subtypes. This review explores the possible roles of GABAergic dysregulation in IBS pathogenesis across multiple levels: in the central nervous system circuits, at the intestinal level, and in the microbiota-gut-brain axis interactions. Moreover, preclinical and limited clinical data regarding possible therapeutic approaches targeting the GABAergic system in IBS are discussed in the review. These include GABA receptor modulators, dietary supplements, probiotics producers of GABA and novel combinations such as GABA–Melissa ofﬁcinalis. However, despite promising results, current evidence on these approaches is limited and mainly based on animal models. Therefore, randomized clinical

FAQs

Why is GABA considered relevant to irritable bowel syndrome (IBS)?

Recent evidence suggests the GABAergic system may contribute to IBS symptom development by modulating visceral pain, intestinal motility, barrier integrity, and immune responses.

How could GABA signaling involve the gut microbiota-gut-brain axis?

The gut microbiota is described as capable of producing GABA, potentially linking microbiota composition to GABAergic tone within the microbiota-gut-brain axis.

What types of therapies are discussed for targeting the GABAergic system in IBS?

The review discusses approaches including GABA receptor modulators, dietary supplements, probiotics that produce GABA, and combinations such as GABA–Melissa officinalis.

Sep 29, 2026

Uploaded by Mabel