Lactiplantibacillus plantarum Lp815 improves sleep and increases urinary GABA in a randomized, double-blind, placebo-controlled study of sleep disturbance

Gamma-aminobutyric acid, or GABA, the major inhibitory neurotransmitter, acts both through the central nervous system and via microbial production in the gut. Strains able to augment gut GABA production could be novel targets for modulation of sleep and mood. We previously demonstrated that Lactiplantibacillus plantarum Lp815 improves symptoms of anxiety. The current study investigates the impact of Lp815 on subjective sleep, mood, digestion and objective wearable sleep data over 6 weeks in adults with self-reported sleep disturbance. The trial was decentralized, double-blind, randomized and placebo controlled. Participants were screened for at least moderate symptoms of insomnia and blindly assigned to receive either a placebo capsule or 5 billion CFU of Lp815 per day. 139 Individuals (5 billion CFU Lp815 n = 70, placebo n = 69) were evaluated, aged 44 ± 13 years, 51.1% female and 55.4% Caucasian. A sub cohort (n = 17, 5 billion CFU Lp815 n = 9, Placebo n = 8) submitted a urinary time series for neurotransmitter analysis. Participants who received 5 billion CFU Lp815 exhibited significantly lower insomnia severity index scores at 6 weeks compared to placebo (p < 0.05). This result was clinically meaningful, with 77.3% of participants in the 5 billion CFU Lp815 cohort exhibiting improvement by 4 + points in their insomnia severity index at week 6, compared to 57.8% in the placebo group (p = 0.02). Anxiety scores were significantly reduced compared to placebo (p < 0.05), with a more pronounced effect among women (p < 0.01). Additionally, subjective night sweat severity decreased, and objective measures of sleep duration were increased in the 5 billion CFU Lp815 cohort compared to placebo (p < 0.05). Finally, the 5 billion CFU Lp815 cohort exhibited an increase in urinary GABA compared to placebo during the first week of use (p < 0.05) and urinary GABA was inversely correlated with insomnia and anxiety scores at week 2 (r²=-0.30 and - 0.48, respectively). All adverse events potentially related to product use were mild. A daily probiotic containing 5 billion CFU Lp815 significantly improved subjective symptoms of insomnia and anxiety, as well as objective measures of sleep after 6 weeks. Elevation of systemic GABA may contribute to these effects.Trial Registration. The trial was approved by Sterling IRB (12481-NACraft) and registered with ClinicalTrials.gov (NCT06789718).