Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS). In recent years, foods rich in GABA have attracted considerable attention, but how they affect brain function has long been a focus of scientific inquiry. Existing research reveals that oral GABA does not simply "reach the brain directly"; instead, it interacts with the body through multiple pathways.

I. Potential Mechanisms of Blood-Brain Barrier (BBB) Permeability

The traditional view holds that GABA has difficulty crossing the BBB effectively, but some studies have proposed new insights, suggesting that GABA may enter the brain in a limited manner through specific mechanisms or under certain conditions.

1.Specific Transporter Proteins:

Studies have found that the BGT-1 protein on the BBB of mice can participate in GABA transport. However, further rigorous experiments are needed to confirm whether GABA can cross the BBB^[1][2].

2.Changes in Permeability:

Under certain pathological conditions, the permeability of the BBB may change, allowing GABA to enter the CNS more easily[2].

3.Effects of GABA Precursors or Metabolites:

It is hypothesized that oral GABA itself may not enter the brain in large quantities, but it may be converted into other compounds capable of crossing the BBB in the body, or indirectly regulate the CNS by affecting the peripheral GABA system[2].

II. Mediated Effects of the Gut-Brain Axis

The gut-brain axis is a complex bidirectional communication system that connects the gut and the brain through multiple pathways including neural, endocrine, and immune pathways. Oral GABA is believed to exert its effects on the CNS primarily through this axis[3].

1.Synergistic Effects of Gut Microbiota:

Intestinal strains such as Lactobacillus and Bifidobacterium can produce endogenous GABA. Oral GABA or GABA-rich foods may affect the composition and function of gut microbiota, thereby regulating the production of endogenous intestinal GABA or indirectly influencing brain function through other metabolites^[4].

2.Vagus Nerve Pathway Transmission:

The gastrointestinal tract contains a large number of GABA-B receptors, and both GABA-A and GABA-B receptors can regulate the release of serotonin (5-HT) from enterochromaffin cells^[5]. 5-HT is an important neurotransmitter and intestinal active substance, widely distributed in the CNS and gastrointestinal tract (the gut is the main site of 5-HT synthesis), and it is involved in regulating various physiological processes such as mood, sleep, intestinal peristalsis, secretory function, and immune responses.

In addition, since the afferent neurons of the vagus nerve also express a large number of GABA-B receptors, upon stimulation, the vagus nerve transmits signals to structures such as the VLPO region, raphe nucleus, and locus coeruleus, regulating the secretion of neurotransmitters in the brain and thus affecting brain function^[2][3].

3.Indirect Regulation Mediated by Metabolites:

GABA produces signaling molecules through intestinal metabolism, which affect the CNS through the bloodstream; or indirectly enhances the activity of the brain GABA system by regulating the levels of neurosteroids and corticosteroids^[2].

III. Indirect Effects of the Peripheral Nervous System (PNS) and Immune System

GABA is not only a neurotransmitter in the CNS but also produced and functional in peripheral tissues, including pancreatic β-cells and immune cells. Oral GABA may indirectly affect the CNS by influencing these peripheral systems.

In summary, oral GABA may affect brain function through multiple pathways, including potential BBB penetration, gut-brain axis mediation, and indirect regulation of peripheral systems, but its specific mechanisms still require further exploration and verification. With the further clarification of research in the future, the application of oral GABA in functional food development and neurohealth maintenance will be more targeted, providing more solid scientific support for relevant health needs.

Next, we will start from the gender specificity of the GABA system and discuss gonadal hormone regulation and differences in stress responses between men and women!

[1] Takanaga H , Ohtsuki S ,Ki,et al.GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier.[J].Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 2001(10):21.

[2] Johnston G A R, Beart P M. Milestone review: GABA, from chemistry, conformations, ionotropic receptors, modulators, epilepsy, flavonoids, and stress to neuro-nutraceuticals [J]. 神经化学杂志，2024, 168: 1179-1192.

[3] Almutairi S , Sivadas A , Kwakowsky A .The Effect of Oral GABA on the Nervous System: Potential for Therapeutic Intervention[J].Nutraceuticals, 2024, 4(2):241-259.DOI:10.3390/nutraceuticals4020015.

[4] Icer M A, Sarikaya B, Kocyigit E, et al. Contributions of Gamma-Aminobutyric Acid (GABA) Produced by Lactic Acid Bacteria on Food Quality and Human Health: Current Applications and Future Prospects[J]. Foods, 2024, 13: 2437.

[5] 韩啸.乳杆菌产γ-氨基丁酸能力分析及其发酵乳改善睡眠效果评价[D].江南大学,2019.