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

Background/Objectives: Recent studies have shown that GABA reduces visceral hypersensitivity and improves intestinal permeability in a post-inflammatory irritable bowel syndrome (IBS) rat model. We aimed to assess the efficacy of a GABA-based supplement in IBS patients with diarrhea (IBS-D), focusing on symptoms relief, quality-of-life improvement, mucosal barrier function, systemic microinflammation and gut microbiota. Methods: In this double-blind, placebo-controlled, crossover study, 20 IBS-D patients were randomized to receive GABA or placebo for two four-week treatment periods separated by a two-week washout. Efficacy was assessed using IBS Symptom Severity Score (IBS-SSS) and Short-Form Health Survey-36 (SF-36). Circulating levels of lipopolysaccharide-binding protein (LBP), Tumor Necrosis Factor-α (TNF-α) and interleukin (IL)-1β were measured before and after each treatment. Results: Eighteen patients completed the study. A clinical response (≥50-point reduction in IBS-SSS) was observed in 66.7% of patients during GABA treatment versus 33.3% with placebo. GABA produced a significant reduction in the IBS-SSS total score (p = 0.02) and in the bowel satisfaction item of the questionnaire (p = 0.02). Regarding quality of life, GABA significantly improved the “Emotional limitation” domain compared with placebo (p = 0.009). GABA treatment also led to a decrease in circulating LBP (p = 0.06) and IL-1β (p = 0.02) levels compared to placebo, although only the reduction in IL-1β reached statistical significance. In contrast, no substantial remodeling of the gut microbiota was observed. Conclusions: In this pilot study, GABA treatment led to a significant improvement in IBS-D symptoms compared with placebo and was also more effective in enhancing emotional wellbeing. GABA appeared to have a possible effect on intestinal permeability indirectly assessed through LBP, consistent with preclinical findings, and significantly reduced systemic inflammation. GABA may represent a promising therapeutic option for IBS, deserving further investigation in larger clinical trials.