Researchers at the University of Pisa and other institutions in Italy also observed a reduction in inflammatory markers but no changes in microbial diversity, leading them to suggest that the supplement’s effects likely stem from barrier and immune modulation.
“GABA may represent a promising therapeutic option for IBS, deserving further investigation in larger clinical trials,” they wrote.
How can GABA support IBS?
IBS can substantially affect quality of life, and patients often report psychological symptoms such as anxiety and depression accompanying their physical symptoms. Despite a wide range of therapeutic strategies, including dietary and lifestyle changes, probiotics, antispasmodics, and antidiarrheals, patients often experience only partial symptom relief. IBS-D patients commonly experience more severe pain, increased intestinal permeability, and low-grade inflammation in the gut lining.
γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, but also acts as a key signaling molecule at a peripheral level.
Previous evidence suggests that GABA modulates immune cell activation and cytokine production, and supports the gut barrier function by reducing inflammation and supporting tight junction integrity.
In pre-clinical models of IBS, a combined formulation of GABA and Melissa officinalis reduced visceral hypersensitivity, reduced oxidative stress, and improved gut barrier integrity, but despite potentially strong mechanisms, the supplement has not been previously evaluated in randomized clinical trials involving patients with IBS-D.
Study details
Researchers randomly assigned 18 participants diagnosed with IBS-D into two groups to receive either GABA or placebo for 4 weeks. The GABA supplement was a tablet containing 250 mg of gamma-aminobutyric acid (GABA) and 50 mg of a dry extract of Melissa officinalis, which was taken three times daily.
Before and after the treatment period, researchers evaluated physical and psychological symptoms using questionnaires and took blood samples and fecal samples for microbiota analysis.
Following a 2-week washout period, the participants crossed over to the other group for the next 4-week treatment, with the same analyses.
There was only a significant difference for the GABA supplement compared to placebo in one domain of the quality-of-life scores, but the researchers noted that this should be interpreted with caution, given the absence of consistent effects in other domains.
An improvement in the irritable bowel syndrome symptom severity score (IBS-SSS) was observed in 66.7% of participants receiving GABA, compared with 33.3% of those receiving placebo. The supplement also resulted in greater improvement in the “Satisfaction with bowel habits” item compared with placebo, but there were no significant differences in the weekly number of bowel movements. Additionally, some inflammatory markers were reduced among the GABA participants.
Although the researchers observed some changes in the microbiota, subsequent analyses did not show significant differences between the treatment groups.
“Thus, despite the clinical efficacy and possible biological modulation of permeability and inflammatory markers, the overall microbiome structure remained largely stable, suggesting that the clinical effect of GABA in this study likely stems from direct GABAergic modulation of barrier/neuroimmune pathways, rather than microbiota remodeling,” they wrote.
They acknowledged the small sample size and other study limitations, suggesting that their preliminary findings require confirmation in adequately powered randomized clinical trials.
Source: Nutrients; doi: 10.3390/nu18101569; “Effects of γ-Aminobutyric Acid (GABA) Supplementation on Symptoms, Quality of Life, Intestinal Permeability, Systemic Inflammation and Gut Microbiota in Patients with IBS-D: A Randomized, Double Blind, Placebo-Controlled, Crossover Pilot Study.” Authors: C. Lambiase et al.