Supplements

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

Q: Did the probiotic improve depression in this study?

No, there was no significant effect of the probiotic compared to placebo on any primary or secondary depression outcomes.

Q: What was the role of formic acid in this study?

Lower baseline fecal formic acid and a greater increase during treatment were associated with reduced depression scores in the probiotic group, suggesting it may be a biomarker or mediator of response.

Q: Who were the participants in this trial?

Overweight adults (BMI ≥25) with major depressive disorder and low-grade inflammation (hs-CRP ≥1 mg/L) who were on stable antidepressant treatment.

Q: How long was the treatment period?

The study lasted 8 weeks, with assessments before and after the intervention.

In an 8-week double-blind RCT, 75 overweight patients with major depressive disorder and systemic low-grade inflammation (hs-CRP ≥ 1 mg/L) received either L. reuteri probiotic or placebo added to stable treatment. No significant effects on depression outcomes (MADRS total score or inflammatory depressive symptoms) were found (all p > 0.25). Exploratory analyses suggested that lower baseline fecal formic acid and greater treatment-associated increase in formic acid were linked to MADRS improvement 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

Söderberg Veibäck G, Lindahl J, Suneson K, Tjernberg J, Ståhl D, Landberg R, Asp M, Kjellberg A, Falknäs F, Sjöberg 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: 40484149 DOI: 10.1016/j.bbi.2025.06.002

Mechanism Graph

Probiotic L. reuteri is hypothesized to produce short-chain fatty acids (SCFAs) with anti-inflammatory properties

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SCFAs, particularly formic acid, may modulate neuroinflammation and depressive symptoms

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Lower baseline fecal formic acid and greater increase during treatment associated with depression improvement

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Result: No overall antidepressant effect, but formic acid may be a biomarker or mediator of response

Limitations

⚠Modified intention-to-treat analysis (n=75) may not reflect full randomized sample
⚠Exploratory nature of formic acid findings requires replication in larger trials
⚠Specific probiotic strain and dose may not be optimal for this population

Frequently Asked Questions

Did the probiotic improve depression in this study?▼

No, there was no significant effect of the probiotic compared to 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 reduced depression scores in the probiotic group, suggesting it may be a biomarker or mediator of response.

Who were the participants in this trial?▼

Overweight adults (BMI ≥25) with major depressive disorder and low-grade inflammation (hs-CRP ≥1 mg/L) who were on stable antidepressant treatment.

How long was the treatment period?▼

The study lasted 8 weeks, with assessments before and after the intervention.

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References

1.Söderberg Veibäck G, Lindahl J, Suneson K, Tjernberg J, Ståhl D, Landberg R, Asp M, Kjellberg A, Falknäs F, Sjöberg 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.