Probiotics' Neurotransmitters in Pain Regulation
DOI:
https://doi.org/10.15407/Keywords:
probiotics, postbiotics , gut microbiota , pain , neurotransmitters, serotonin, gamma-aminobutyric acid, dopamine, glutamate, acetylcholineAbstract
Pain, affecting over one-fifth of the global population, remains a major medical and social challenge that necessitates the development of safe and effective strategies for its prevention and management. Recent studies highlight the pivotal role of the gut microbiota and probiotics in modulating pain through neurochemical, immune, and metabolic pathways along the gut–brain axis. Probiotics can synthesize key neurotransmitters—including γ-aminobutyric acid (GABA), serotonin (5-HT), dopamine, glutamate, and acetylcholine—thereby influencing neuronal excitability, neuroinflammation, and pain perception. GABA-producing lactic acid bacteria, particularly representatives of the genera Lactobacillus, Bifidobacterium, and Levilactobacillus brevis, are successfully employed in the biotechnological production of functional foods such as GABA-enriched yogurt, soy milk, and rice vinegar etc. These strains contribute to analgesic effects through inhibition of neuronal hyperexcitability, cytokine suppression, and enhancement of endogenous pain inhibition mechanisms. Similarly, probiotic modulation of serotonergic signaling involves increased tryptophan hydroxylase (TPH1) expression, regulation of the serotonin transporter (SERT), and activation of 5-HT receptors, thereby reducing visceral hypersensitivity and pain transmission. Probiotic species such as Enterococcus faecium and Lactiplantibacillus plantarum influence dopaminergic pathways by converting L-DOPA to dopamine, modulating gut–brain signaling and neuroinflammation relevant to chronic pain and neurodegenerative disorders. Moreover, glutamate metabolism by probiotic strains helps maintain the excitatory/inhibitory neurotransmitter balance via glutamate decarboxylase activity, contributing to neuroprotection and attenuation of excitotoxicity. Acetylcholine-producing probiotics activate the cholinergic anti-inflammatory pathway, reduce systemic inflammation, and modulate sensory signaling along the enteric and central nervous systems. Altogether, these findings demonstrate that neurotransmitter-producing probiotics represent a promising frontier for microbiota-based strategies in chronic pain management. By integrating food biotechnology, neurobiology, and microbial endocrinology, future probiotic formulations could offer natural, safe, and effective therapeutic approaches for modulating pain perception through the gut–brain axis.
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