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).
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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
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 supplementation alters gut microbiota composition
- ▸Increased production of short-chain fatty acids (e.g., formic acid)
- ▸Formic acid exerts anti-inflammatory effects
- ▸Reduction in depressive symptoms in a subset of patients with low baseline formic acid
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
Not specified in abstract
Limitations & Caveats
Important context when interpreting this evidence:
- ▸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.
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