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

2025-12
Nutrition (Burbank, Los Angeles County, Calif.) 140

PubMed: 40729791
DOI: 10.1016/j.nut.2025.112891

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 39
Population: 39 participants ... Australian adults with subthreshold depression
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.

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.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus rhamnosus LR06	—	Increased Plasma Serotonin Levels	Beneficial	Small	View source 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.
Lactobacillus rhamnosus LR06	—	No Change in Plasma GABA Levels	Neutral	Small	View source No significant changes were observed for plasma GABA concentrations.