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

Area of Science:

• Neuroscience
• Microbiome Research
• Psychiatry

Background:

• Previous studies suggest probiotics may have antidepressant effects, but high-quality trials are lacking.
• Mechanisms are unclear, but short-chain fatty acids (SCFAs), like formic acid, are potential mediators due to their anti-inflammatory properties.

Purpose of the Study:

• To evaluate the antidepressant efficacy of a Lactobacillus probiotic as an adjunctive treatment in depressed patients with low-grade systemic inflammation.
• To investigate the relationship between treatment response and SCFA levels in blood and feces.

Main Methods:

• An 8-week, double-blind, randomized controlled trial (RCT) involving patients with major depressive disorder (MDD), BMI ≥ 25 kg/m², and hs-CRP ≥ 1 mg/L.
• Participants received either Limosilactobacillus reuteri (L. reuteri) or a placebo, alongside stable standard treatment.
• Primary outcomes included changes in Montgomery-Åsberg Depression Rating Scale (MADRS) and "inflammatory depressive symptoms"; SCFAs were analyzed in blood and feces.

Main Results:

• No significant antidepressant effects of L. reuteri were observed compared to placebo on primary or secondary outcomes in the modified intention-to-treat analysis (n=75).
• Lower baseline fecal formic acid and a greater increase during treatment were significantly associated with reduced MADRS scores in the probiotic group (p < 0.01).
• Preliminary evidence suggests formic acid may serve as a biomarker or mediator of treatment response.

Conclusions:

• Adjunctive L. reuteri probiotic did not demonstrate overall antidepressant effects in overweight depressed patients with systemic inflammation.
• Formic acid, an anti-inflammatory SCFA, shows potential as a biomarker for predicting treatment response in depression.
• Further research is needed to elucidate the role of specific SCFAs in the gut-brain axis and their impact on depressive symptoms.