Leaky Gut Biomarkers as Predictors of Depression and Suicidal Risk: A Systematic Review and Meta-Analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control and cross-sectional studies
PubMed 40647682 · doi:10.3390/diagnostics15131683
What was done
A systematic review and random-effects meta-analysis evaluated studies examining biomarkers of intestinal permeability or gut inflammation in individuals with depressive symptoms or suicidality. Eligible studies compared depressive or suicidal patients to controls, compared suicidal to non-suicidal patients, or assessed correlations between biomarker levels and depressive symptom severity. Effect sizes were pooled using Hedges' g, and heterogeneity was assessed using the I² index.
What was found
Twenty-two studies were included in the meta-analysis. Compared to healthy controls, patients with depression had significantly elevated levels of intestinal fatty acid-binding protein (I-FABP: ES = 0.36, 95% CI 0.11 to 0.61, p = 0.004, I² = 71.61%), zonulin (ES = 0.69, 95% CI 0.02 to 1.36, p = 0.044, I² = 92.12%), antibodies against bacterial endotoxins (ES = 0.75, 95% CI 0.54 to 0.98, p < 0.001, I² = 0.00%), and sCD14 (ES = 0.11, 95% CI 0.01 to 0.21, p = 0.038, I² = 10.28%). No significant differences were observed for LPS-binding protein (LBP) or alpha-1 antitrypsin (A-1-AT). For suicidality (4 quantitative studies), I-FABP levels did not differ significantly between suicidal patients and controls (ES = 0.24, 95% CI -0.30 to 0.79, p = 0.378, I² = 86.44%). Nineteen studies examining symptom-biomarker correlations yielded inconclusive results.
Why it matters
This meta-analysis quantitatively demonstrates an association between elevated biomarkers of gut barrier dysfunction/endotoxin exposure and depression, while showing that current evidence does not support an association with suicidal risk.
Limits
The included studies were observational and cross-sectional, preventing causal conclusions. Several primary biomarker analyses exhibited extreme statistical heterogeneity (zonulin I² = 92.12%, I-FABP I² = 71.61% in depression and 86.44% in suicidality). Suicidality data were restricted to very few studies, and correlation analyses across the literature remained inconclusive.
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