Add-on Limosilactobacillus reuteri probiotic does not improve depressive symptoms in overweight depressed patients with systemic low-grade inflammation
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).
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Add-on Limosilactobacillus reuteri probiotic does not improve depressive symptoms in overweight depressed patients with systemic low-grade inflammation The current body of evidence comprises 1 study, including 1 randomized controlled trial. EvidenceHub rates the overall confidence at 48/100 (low).
The Claim
Add-on Limosilactobacillus reuteri probiotic does not improve depressive symptoms in overweight depressed patients with systemic low-grade inflammation
This conclusion is most relevant to: Overweight (BMI ≥ 25 kg/m²) adults with major depressive disorder and systemic low-grade inflammation (hs-CRP ≥ 1 mg/L).
What the Research Shows
The conclusion draws on 1 linked study. Highlights from the cited literature:
- ▸Add-on probiotics for inflammatory depression - A double-blind randomized placebo-controlled trial. (Brain, behavior, and immunity, 2025) —
How It Works
The proposed biological pathway:
- ▸Probiotic L. reuteri is hypothesized to produce short-chain fatty acids (SCFAs) with anti-inflammatory properties
- ▸SCFAs, particularly formic acid, may modulate neuroinflammation and depressive symptoms
- ▸Lower baseline fecal formic acid and greater increase during treatment associated with depression improvement
- ▸Result: No overall antidepressant effect, but formic acid may be a biomarker or mediator of response
Who Might Benefit
Evidence fit by population:
- ▸Overweight (BMI ≥ 25 kg/m²) adults with major depressive disorder and systemic low-grade inflammation (hs-CRP ≥ 1 mg/L)
Recommended Dose
N/A (specific dose not reported in abstract)
Limitations & Caveats
Important context when interpreting this evidence:
- ▸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.
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