GABA and GABAergic interventions are commonly used for sleep, mood regulation, and pain management. One of the ways the gut-brain axis regulates mood, stress, and sleep is via bacterial neurotransmitter, hormone, and metabolite production. The gut-brain axis works bidirectionally, with sleep disturbances negatively impacting microbiome health.
Several bacterial strains produce the inhibitory neurotransmitter GABA; however, the amount of GABA production varies among strains. Probiotics may offer a safe alternative or adjunct to traditional sleep medications for managing insomnia.
Lactobacillus Plantarum Sleep Study
A randomized, double-blind, placebo-controlled study published in Nature Scientific Reports¹ showed improved sleep after 6 weeks on a probiotic. 139 participants with moderate to severe insomnia were randomized to receive either placebo or 5 billion CFU of Lactiplantibacillus plantarum Lp815 (formerly Lactobacillus plantarum) daily.
Participants were instructed to wear a Gen3 Oura Ring to collect objective sleep data throughout the study. The Oura Ring correlates well with traditional polysomnography. At baseline, they also completed several other measures, including an Insomnia Severity Index (ISI), Generalized Anxiety Disorder 7-Item Questionnaire (GAD-7), the Gastrointestinal Symptom Rating Scale (GSRS), and daily survey questions regarding sleep, night sweats, mood, and quality of life. The ISI, GAD-7, and GSRS were repeated biweekly.
Lp815 has known GABA-producing capability, which is why it was chosen for this study. Prior in-vitro evaluation showed that 5 billion CFU of this probiotic should produce 500 mg GABA per day.
A smaller cohort within the study submitted first morning urine samples for neurotransmitter testing, including GABA, serotonin, dopamine, norepinephrine, epinephrine, glutamate, glycine, histamine, and phenethylamine (PEA). First morning urine reflects overnight neurotransmitter production during sleep, versus a single timepoint using serum during waking hours.
Compared to placebo, individuals taking the probiotic had:
- Significantly lower ISI scores (p < 0.05) with statistical improvements in falling asleep and staying asleep; ISI scores were inversely correlated to GABA concentration after 2 weeks
- Significantly lower anxiety scores (p < 0.05) that were greater among women (p < 0.01) and participants with more severe baseline insomnia symptoms; GAD-7 scores were inversely correlated to GABA concentration after 2 weeks
- Increased measures of sleep duration (p < 0.05), including time in bed, total sleep, and deep sleep duration
- Increase in urinary GABA (p < 0.05)
- Decreased night sweat severity (p < 0.05)
The sleep benefits are thought to be connected to GABA production, which acts as an inhibitory neurotransmitter, relieving anxiety and promoting sleep. Lp815 has known GABA-producing capability, which is why it was chosen for this study. Prior in-vitro evaluation showed that 5 billion CFU of this probiotic should produce 500 mg GABA per day. A limited amount of gut-derived GABA crosses the blood–brain barrier. Instead, it may influence brain function more indirectly by modulating vagus nerve signaling, in contrast to GABA produced within the brain.
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What About Other Probiotic Strains?
A recent systematic review and meta-analysis² in Frontiers in Microbiology explored the impact of probiotics on sleep quality and mood in patients with insomnia. The review looked at several studies, which covered several different types of probiotics, including Lactobacillus, Bifidobacterium, Saccharomyces, Clostridium, and others. The meta-analysis results showed that probiotics improved sleep quality with a significantly reduced Pittsburgh Sleep Quality Index (PSQI) score compared to placebo or no treatment. It also showed reduced depressive symptoms in patients with insomnia.
Conclusions
In addition to enhancing GABA and other neurotransmitters and hormones, probiotics promote the production of short-chain fatty acids (SCFAs), which can stimulate the vagus nerve and influence neural activity in sleep-related brain regions. They also help reduce inflammation. These mechanisms are thought to contribute to improved sleep and mood in patients who struggle with insomnia, making probiotics a safe and effective treatment consideration.
→ Download Full Text of Nature Scientific Reviews study HERE.
→ Download Full Text of Frontiers in Microbiology study HERE.
References
- Grant, A.D., Erfe, M.C.B., Delebecque, C.J. et al. Lactiplantibacillus plantarum Lp815 improves sleep and increases urinary GABA in a randomized, double-blind, placebo-controlled study of sleep disturbance. Sci Rep 16, 644 (2026). https://doi.org/10.1038/s41598-025-27861-6
- Liu Y, Yu Y, Lu S, Tan K, Jiang P, Liu P and Peng Q (2025) Impact of probiotics on sleep quality and mood states in patients with insomnia: a systematic review and meta-analysis. Front. Microbiol. 16:1596990. doi: 10.3389/fmicb.2025.1596990
