Production of Gamma (γ)-Aminobutyric Acid by Lactic Acid Bacteria and Its Applications in the Food and Health Sectors

Gamma (γ)-aminobutyric acid (GABA) is a non-proteinogenic amino acid recognized for its primary function as the main inhibitory neurotransmitter in the mammalian central nervous system and its role as a stress-responsive metabolite in various microorganisms. This review critically examines the biosynthesis of GABA by lactic acid bacteria (LAB) via the glutamate decarboxylase (GAD) system and evaluates its potential applications in food and health sectors. The mechanistic details of the GAD pathway are analyzed, focusing on the integrated roles of gadA/gadB decarboxylases, the gadC antiporter, and pyridoxal−5′-phosphate (PLP) dependency in relation to acid resistance, metabolic flux, and strain variability. Taxonomic and strain-level diversity among GABA-producing LAB is assessed, with emphasis on the highly strain-specific nature of GABA production rather than broad species or genus generalizations. Fermentation optimization parameters (pH, temperature, substrate loading, and cofactor management) and scale-up challenges, including techno-economic feasibility and downstream recovery efficiency, are critically evaluated. Integration of LAB-derived GABA into fermented food matrices is discussed with attention to sensory compromises, stability, regulatory factors, and clean-label considerations. Evidence from clinical and preclinical studies is synthesized to assess the physiological significance of dietary GABA, distinguishing between purified GABA supplementation, GABA-enriched fermented foods, and probiotic effects of live LAB, while addressing the GABA paradox and gut–brain axis interactions. Significant research gaps are identified, including the need for standardized quantification methodologies, multi-omics-guided strain engineering, predictive bioprocess modeling, and rigorously designed human trials in realistic food matrices. This review provides a systems-oriented, critical framework to promote scalable and evidence-based advancement of GABA-enriched functional foods.