Lactobacillus reuteri E9 Regulates Sleep Disorders Through Its Metabolite GABA.

BACKGROUND: Insomnia, the most prevalent sleep disorder, is clinically defined as difficulty initiating or maintaining sleep. Although many medications are effective for insomnia treatment, they carry risks of drug dependence and abuse. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signaling between the gastrointestinal tract and the central nervous system via gut microbes. Probiotics that provide mental and behavioral benefits through MGBA (psychobiotics) offer broad therapeutic potential. METHODS: A non-toxic, drug-resistant strain of Lactobacillus reuteri E9 was isolated and characterized. Its effects were evaluated in a pentylenetetrazol (PTZ)-induced zebrafish model of sleep disorder. Neurotransmitter levels (glycine, serine, taurine, γ-aminobutyric acid (GABA)) and gene expression of GABA/melatonin receptors were analyzed. RESULTS: E9 significantly upregulated inhibitory neurotransmitters, including GABA, taurine, glycine, and serine (p < 0.05). In PTZ-induced zebrafish, E9 exerted sedative effects by reducing seizures and hyperactivity. Concurrently, E9 upregulated the expression of GABA receptor genes and melatonin receptor (Mtnr1aa) genes in zebrafish neural tissue. CONCLUSIONS: Lactobacillus reuteri E9 demonstrates potential as a psychobiotic for sleep disorder management by modulating key inhibitory neurotransmitters and sleep-related receptor expression via the MGBA pathway, offering a non-pharmacological alternative to conventional treatments.