Gamma-aminobutyric acid (GABA) plays a crucial role in the central nervous system as an inhibitory neurotransmitter. Imbalances in GABA levels are associated with neurological and psychological disorders. Recent research suggests that GABA can cross the blood-brain barrier and influence brain function, particularly through changes in gut microbiota composition. This review covers the latest findings on GABA-producing microorganisms isolated from the human gut and fermented foods, their role in mediating the gut-brain axis, and their potential in treating neurological and psychological disorders. Key points include: 1. **GABA Metabolism and Synthesis**: GABA is synthesized from glutamate by glutamate decarboxylase (GAD) enzymes, which require pyridoxal-5′-phosphate (PLP) as a cofactor. GAD enzymes exist in two forms, GAD65 and GAD67, and are regulated by GAD1 and GAD2 genes. 2. **GABA Degradation**: GABA is catabolized to succinic semialdehyde (SSA) by GABA-transaminase (GABA-T) and further oxidized to succinate by SSA dehydrogenase (SSADH). 3. **GABA-Producing Microorganisms**: - **Human Gut**: *Bifidobacterium*, *Lactobacillus*, and *Bacteroides* are well-known GABA producers. *Bacteroides* is particularly abundant and influential in mental health through GABA regulation. - **Fermented Foods**: Lactic acid bacteria (LAB) from fermented foods like cheese, yogurt, and kimchi are efficient GABA producers. 4. **Food Factors Inducing GABA Production**: Dietary factors such as proteases from Aspergillus oryzae and lipases from Penicillium camemberti can enhance the abundance of GABA-producing probiotics in the gut. 5. **GABA as a Mediator of the Gut-Brain Axis**: - **Neurological Disorders**: GABA levels and gut microbiota composition are linked to conditions like schizophrenia, Alzheimer's, and Parkinson's disease. - **Mental Health**: GABA is associated with anxiety, depression, and stress. Probiotic supplementation can improve cognitive function and reduce symptoms in patients with neurological disorders. - **Epilepsy**: A ketogenic diet and probiotic administration can increase GABA levels and improve seizure control. 6. **Homocarnosine**: A GABA-containing dipeptide, homocarnosine, is predominantly found in the brain. It acts as a protective agent against various diseases and may be a downstream mediator of GABA in the gut-brain axis. This review highlights the potential of GABA and homocarnosine in modulating brain function and treating neurological and psychological disorders, emphasizing the importance of further research onGamma-aminobutyric acid (GABA) plays a crucial role in the central nervous system as an inhibitory neurotransmitter. Imbalances in GABA levels are associated with neurological and psychological disorders. Recent research suggests that GABA can cross the blood-brain barrier and influence brain function, particularly through changes in gut microbiota composition. This review covers the latest findings on GABA-producing microorganisms isolated from the human gut and fermented foods, their role in mediating the gut-brain axis, and their potential in treating neurological and psychological disorders. Key points include: 1. **GABA Metabolism and Synthesis**: GABA is synthesized from glutamate by glutamate decarboxylase (GAD) enzymes, which require pyridoxal-5′-phosphate (PLP) as a cofactor. GAD enzymes exist in two forms, GAD65 and GAD67, and are regulated by GAD1 and GAD2 genes. 2. **GABA Degradation**: GABA is catabolized to succinic semialdehyde (SSA) by GABA-transaminase (GABA-T) and further oxidized to succinate by SSA dehydrogenase (SSADH). 3. **GABA-Producing Microorganisms**: - **Human Gut**: *Bifidobacterium*, *Lactobacillus*, and *Bacteroides* are well-known GABA producers. *Bacteroides* is particularly abundant and influential in mental health through GABA regulation. - **Fermented Foods**: Lactic acid bacteria (LAB) from fermented foods like cheese, yogurt, and kimchi are efficient GABA producers. 4. **Food Factors Inducing GABA Production**: Dietary factors such as proteases from Aspergillus oryzae and lipases from Penicillium camemberti can enhance the abundance of GABA-producing probiotics in the gut. 5. **GABA as a Mediator of the Gut-Brain Axis**: - **Neurological Disorders**: GABA levels and gut microbiota composition are linked to conditions like schizophrenia, Alzheimer's, and Parkinson's disease. - **Mental Health**: GABA is associated with anxiety, depression, and stress. Probiotic supplementation can improve cognitive function and reduce symptoms in patients with neurological disorders. - **Epilepsy**: A ketogenic diet and probiotic administration can increase GABA levels and improve seizure control. 6. **Homocarnosine**: A GABA-containing dipeptide, homocarnosine, is predominantly found in the brain. It acts as a protective agent against various diseases and may be a downstream mediator of GABA in the gut-brain axis. This review highlights the potential of GABA and homocarnosine in modulating brain function and treating neurological and psychological disorders, emphasizing the importance of further research on