Exploring neurotransmitter regulation following probiotic supplementation in adults with subthreshold depression: A secondary analysis of a randomized controlled trial

Nutrition. 2025 Jun 29;140:112891. doi: 10.1016/j.nut.2025.112891. Online ahead of print.

ABSTRACT

OBJECTIVE: This secondary analysis examined changes in plasma concentrations of gamma-aminobutyric acid (GABA) and serotonin following multi-species probiotic supplementation versus placebo in Australian adults with subthreshold depression and investigated the potential relationships between neurotransmitter changes and mental health outcomes.

METHODS: In a 12-week, double-blind, randomized, placebo-controlled trial, 39 participants took daily doses of one capsule (i.e., placebo or probiotic) containing 4 × 109 CFU of lyophilized strains: Limosilactobacillus fermentum LF16 (DSM26956), Lacticaseibacillus rhamnosus LR06 (DSM21981), Lactiplantibacillus plantarum LP01 (LMG P-21021) and Bifidobacterium longum 04 (DSM23233). Data collected at baseline, 6 and 12 weeks of intervention included validated self-reported questionnaires measuring psychometric symptom severity and plasma concentrations of two neurotransmitters (i.e., GABA and serotonin). Repeated measures ANOVA and mediation analyses were performed.

RESULTS: Plasma serotonin concentrations significantly increased at 6 weeks in both probiotic and placebo groups (2.5 (95% CI 1.3; 3.8) and 2.3 (95% CI 1.0; 3.6), respectively) but only in the placebo group (4.9 [95% CI 1.5; 8.3]) at 12 weeks. No significant changes were observed for plasma GABA concentrations.

CONCLUSIONS: An inverse regulation, leading to decreased plasma serotonin levels, was observed after 6 weeks of supplementation with the probiotic formulation. As evidenced by preclinical and clinical trials, these changes observed in the probiotic group resemble the effect of antidepressant medication and specifically selective serotonin reuptake inhibitors on plasma serotonin concentrations. Our findings support the notion that probiotic supplementation is a safe and preventative option for severe depressive disorder development particularly in high-risk individuals such as people with subthreshold depression.

PMID:40729791 | DOI:10.1016/j.nut.2025.112891