Supplements

Add-on Limosilactobacillus reuteri probiotic does not reduce depressive symptoms in overweight depressed patients with systemic low-grade inflammation

In an 8-week double-blind RCT, 75 patients with major depressive disorder, BMI ≥25 kg/m2, and hs-CRP ≥1 mg/L received either L. reuteri probiotic or placebo added to stable treatment. No significant effects were found on any primary or secondary outcomes (all p > 0.25). Lower baseline fecal formic acid and greater treatment-associated increase in fecal formic acid were significantly associated with MADRS score reduction in the probiotics group (p < 0.01).

Last updated: Aug 26, 2026•1 RCTs•📖 Read as article →

Evidence Score

Evidence Score48/100
Human RCT★★☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Add-on probiotics for inflammatory depression - A double-blind randomized placebo-controlled trial.

observational

S&#xf6;derberg Veib&#xe4;ck G, Lindahl J, Suneson K, Tjernberg J, St&#xe5;hl D, Landberg R, Asp M, Kjellberg A, Falkn&#xe4;s F, Sj&#xf6;berg K, Lavebratt C, Wolkowitz OM, Lindqvist D · Brain, behavior, and immunity (2025)

Participants: N/A
Duration: 8 weeks
Intervention: Limosilactobacillus reuteri probiotic supplement added to regular and stable antidepressant treatment
Outcome: Montgomery-Åsberg Depression Rating Scale (MADRS) total score, inflammatory depressive symptoms composite score (sleep disturbance, energy levels, appetite disturbance), anxiety symptoms, anhedonia, insomnia, fatigue, gastrointestinal symptoms, and fecal/blood short-chain fatty acids
Effect Size: N/A (no significant effects on primary or secondary outcomes)
Population: Overweight (BMI ≥25 kg/m2) patients with major depressive disorder and systemic low-grade inflammation (hs-CRP ≥1 mg/L)

Result:

PubMed: 40484149DOI: 10.1016/j.bbi.2025.06.002

Mechanism Graph

Probiotic supplementation increases fecal formic acid levels
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Formic acid has anti-inflammatory properties
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Lower baseline formic acid and greater increase in formic acid correlate with depression improvement
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Result: Preliminary evidence for formic acid as a biomarker and possible mediator of treatment response

Limitations

  • ⚠No overall antidepressant effect observed, limiting generalizability
  • ⚠Preliminary evidence for formic acid as mediator requires further validation
  • ⚠Modified intention-to-treat analysis may introduce bias

Frequently Asked Questions

Did the probiotic improve depression in this study?▼

No, there were no significant effects of probiotics relative to placebo on any primary or secondary outcomes.

What was the role of formic acid in this study?▼

Lower baseline levels and a greater increase in fecal formic acid were significantly associated with depression improvement in the probiotics group, suggesting it may be a biomarker or mediator.

Who was eligible for this trial?▼

Patients with major depressive disorder, BMI ≥25 kg/m2, and high-sensitivity C-reactive protein ≥1 mg/L.

What type of probiotic was used?▼

Limosilactobacillus reuteri (L. reuteri) probiotic supplement.

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References

  1. 1.S&#xf6;derberg Veib&#xe4;ck G, Lindahl J, Suneson K, Tjernberg J, St&#xe5;hl D, Landberg R, Asp M, Kjellberg A, Falkn&#xe4;s F, Sj&#xf6;berg K, Lavebratt C, Wolkowitz OM, Lindqvist D. "Add-on probiotics for inflammatory depression - A double-blind randomized placebo-controlled trial.." Brain, behavior, and immunity, 2025. PMID: 40484149 DOI: 10.1016/j.bbi.2025.06.002
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.