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

In an 8-week double-blind RCT, add-on L. reuteri probiotic showed no significant effect on depressive symptoms (MADRS score) or inflammatory depressive symptoms compared to placebo in MDD patients with BMI ≥25 and hs-CRP ≥1 mg/L. However, lower baseline fecal formic acid and greater treatment-associated increase in fecal formic acid were significantly associated with MADRS reduction in the probiotic group (p<0.01).

Last updated: Jul 7, 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 alters gut microbiota composition
↓
Increased production of short-chain fatty acids (e.g., formic acid)
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Formic acid exerts anti-inflammatory effects
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Reduction in depressive symptoms in a subset of patients with low baseline formic acid

Limitations

  • ⚠No overall antidepressant effect observed, limiting clinical applicability
  • ⚠Preliminary evidence for formic acid as biomarker; not a confirmed mediator
  • ⚠Modified intention-to-treat analysis may introduce bias

Frequently Asked Questions

Did the probiotic improve depression in this study?▼

No, there was no significant difference between probiotic and placebo on any primary or secondary depression outcomes.

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

Lower baseline fecal formic acid and a greater increase during treatment were associated with better antidepressant response in the probiotic group, suggesting formic acid may be a biomarker of treatment response.

Who were the participants in this trial?▼

Overweight adults (BMI ≥25) with major depressive disorder and elevated inflammation (hs-CRP ≥1 mg/L).

Is this study strong enough to recommend probiotics for depression?▼

No, the null results indicate that L. reuteri probiotics are not effective as an add-on treatment for this specific patient group.

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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.