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GABA, Glutamate, and the Microbiome: Inhibition vs Excitation

Lactobacillus and Bifidobacterium produce GABA, the chief inhibitory neurotransmitter; microbiota GABA regulates enteric nervous system function.

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Bacterial Balance in Neural Signalling

Gamma-aminobutyric acid (GABA) serves as the central nervous system's primary inhibitory neurotransmitter. Remarkably, specific commensal bacteria, particularly Lactobacillus and Bifidobacterium species, synthesise and release GABA directly into the intestinal lumen, contributing meaningfully to the enteric GABA pool.

Bacterial GABA synthesis occurs through the GABA shunt pathway. The enzyme glutamate decarboxylase (GAD), present in numerous bacterial species, catalyses the direct decarboxylation of glutamate to GABA. Lactobacillus brevis, L. plantarum, and Bifidobacterium dentium express active GAD enzymes and produce measurable GABA under intestinal fermentation conditions.

Bravo et al.'s landmark 2011 paper showed that L. rhamnosus JB-1 strain, a probiotic conferring anxiety-reducing effects, acts partly through GABA production. Mice colonised with this strain showed increased hippocampal GABA; this anxiolytic effect completely disappeared after vagotomy, proving vagal transmission necessary. Bacteria cannot reach the brain, but their GABA production modulates enteric signalling, which vagal afferents then convey to the brain as intestinal homeostasis signal.

The enteric nervous system possesses abundant GABA receptors on myenteric and submucosal neurons, regulating secretion and motility. GABA-ergic inhibitory interneurons tonically suppress acetylcholine-producing motor neurons unless stimulated; elevated GABA availability enhances inhibitory tone.

Glutamate acts as the primary excitatory neurotransmitter. Excessive glutamate drives neuroinflammation and can precipitate neurotoxicity. Dysbiotic microbiota produce elevated glutamate through proteolytic protein breakdown. The glutamate-GABA balance determines overall neural tone.

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Fuentes & referencias

  1. Belelli D et al. (2024) From bugs to brain: unravelling the GABA signalling networks in the brain-gut-microbiome axis Brain PMID: 39716883
  2. Conn KA et al. (2024) Implications of microbe-derived γ-aminobutyric acid (GABA) in gut and brain barrier integrity and GABAergic signaling in Alzheimer's disease Gut Microbes PMID: 39008552
  3. Hans Raskov a, Jakob Burcharth et al (2014) Irritable bowel syndrome, the microbiota and the gut-brain axis J Gastroenterol PMID: 27472486
  4. Mayer EA et al. (2023) The neurobiology of irritable bowel syndrome Mol Psychiatry PMID: 36732586
  5. Casertano M et al. (2022) Psychobiotics, gut microbiota and fermented foods can help preserving mental health Food Research International PMID: 35181072
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