A key neurotransmitter in the central nervous system (CNS) is gamma-aminobutyric acid, otherwise known as GABA. Although the inhibitory role of GABA in reducing neuronal excitability is well established, emerging research has highlighted the significance of GABA beyond the brain and CNS. The “gut-brain axis” refers to the bidirectional communication network between the CNS and the gastrointestinal (GI) tract, and GABA plays an important role in this interaction [1-3]. Imbalances of this neurotransmitter are associated with neurological diseases, such as Alzheimer’s and Parkinson’s disease, and psychological disorders, including anxiety, depression, and stress [4]. This article seeks to improve your understanding of the role of GABA in gut health and offers insights into the management of GI disorders, mental health, and overall wellness.
We have previously covered GABA's role in the immune system here. You can also read more on some natural ways to increase GABA here or see if you possibly have GABA deficiency here.
An Overview of GABA Synthesis and Function
GABA is synthesized in the CNS via the decarboxylation of glutamate by the enzyme glutamate decarboxylase [5]. However, GABA can also be produced in the gut by selected species of gut microbiota, such as Lactobacillus and Bifidobacterium [4,6]. The production of GABA in the gut occurs through a similar pathway, and gut-derived GABA influences not only local functions in the GI tract but also brings about systemic and neurological effects.
GABA exerts its action by binding to two major types of receptors, GABA-A and GABA-B. GABA-A receptors are ionotropic, controlling chloride channels, whereas GABA-B receptors are metabotropic and influence intracellular signaling cascades [7]. These receptors can be found in the brain and CNS but also along the enteric nervous system (ENS) [8] which governs GI motility, secretion, and immune function [9].
GABA and the “Gut-Brain Axis”
The bidirectional signaling network linking the GI tract with the CNS (termed the “gut-brain axis”) operates through neuronal, immune, and endocrine pathways. In recent years, the role of GABA in this relationship has become a focal point of research, particularly concerning our understanding of how gut health influences mental health and vice versa [10,11].
Certain gut microbiota species produce GABA, which can influence local gut function and indirectly affect the CNS [12]. For instance, Lactobacillus rhamnosus has been shown to produce GABA, and its presence in the gut has been associated with reduced anxiety-like behaviors in animal studies [13].
Gut-derived GABA can stimulate the vagus nerve, a direct communication highway between the gut and brain, potentially modifying brain function and reducing anxiety and depressive symptoms. Elsewhere, GABA can influence the immune system by modulating cytokine release, the signaling proteins involved in a wide array of immune system processes. The inflammation seen in irritable bowel syndrome (IBS) and other GI problems has been linked with disruptions in GABA signaling [14,15].
The Role of GABA and the Gut on Mental Health
The link between gut health and mental health has been well established, with GABA being a key mediator in this relationship [9,16].
Chronic stress is known to alter the composition of microbiota in the gut, reducing the abundance of GABA-producing bacteria like Lactobacillus and Bifidobacterium which may contribute to anxiety and depressive symptoms via the gut-brain axis.
Human studies to date have shown that the gut microbiome is altered in major depression, alongside disruptions in GABA signaling. As GABA-producing bacteria like Bifidobacterium decrease, hippocampal levels of GABA are also likely to decrease, therefore highlighting one mechanism of action for the gut-brain relationship [17].
The Therapeutic Potential of GABA in Gut Health
In light of its effects on gut-brain crosstalk, GABA has received attention as a potential therapeutic target with the goal of improving both gut and mental health. Several approaches are currently being tested and explored.
Supplementation with probiotics containing GABA-producing strains like Lactobacillus rhamnosus has been shown to improve mood, reduce anxiety, and enhance gut health [13]. Other strains have offered promise for enhancing the microbiota composition and the production of neuroactive metabolites that may have benefits for mental health [18].
Oral GABA supplements are widely marketed for stress reduction, sleep improvement, and gut health [19], however, the ability of GABA to cross the blood-brain barrier is debated and there are issues relating to the bioavailability of such supplements (read more on this here). Nonetheless, oral GABA may act on the enteric nervous system of the GI tract to bring about beneficial effects but these are yet to be consistently and convincingly demonstrated.
Lastly, certain foods such as fermented products like kimchi and yogurt are rich sources of GABA. The consumption of these foods may enhance gut-derived GABA production and support gut and brain health downstream [20].
Conclusion
This article has explored the role of GABA in gut health, which is a rapidly growing field of interest, offering insights into the intricate interplay between the gut microbiota and the brain. By influencing gut motility, visceral sensitivity, and immune system interactions, GABA impacts both GI and mental health.
Probiotic strains and dietary interventions that are aimed at influencing GABA and its production appear to be promising therapeutic strategies. Future research will enhance our understanding of the mechanisms underpinning the impact of GABA on the gut-brain axis and highlight potential avenues and treatments for GI and mental health disorders.
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