The intestinal barrier has recently gained attention as a contributor to the pathophysiology of depression. This narrative review examines the current literature on blood-based markers of intestinal permeability in patients with depression. A structured search of PubMed and EMBASE was performed. Both recent and older studies were included to capture key mechanisms and theoretical foundations. We focused on zonulin, intestinal fatty acid-binding protein (I-FABP), lipopolysaccharides (LPS), LPS-binding protein (LBP), and soluble CD14 (sCD14). While several studies report altered intestinal permeability markers in individuals with depression, results remain inconsistent. Factors such as small sample sizes and variability in measurement procedures complicate interpretation. In some cases, altered biomarker levels were associated with disease severity or response to antidepressant treatment, suggesting a potential role in patient stratification. However, current evidence does not support their routine use in clinical settings. Further research is needed to clarify their value in psychiatric populations. If validated, these markers may help identify inflammation-related depression subtypes and guide more precise treatment strategies.

The intestinal barrier has recently gained attention as a contributor to the pathophysiology of depression. This narrative review examines the current literature on blood-based markers of intestinal permeability in patients with depression. A structured search of PubMed and EMBASE was performed. Both recent and older studies were included to capture key mechanisms and theoretical foundations. We focused on zonulin, intestinal fatty acid-binding protein (I-FABP), lipopolysaccharides (LPS), LPS-binding protein (LBP), and soluble CD14 (sCD14). While several studies report altered intestinal permeability markers in individuals with depression, results remain inconsistent. Factors such as small sample sizes and variability in measurement procedures complicate interpretation. In some cases, altered biomarker levels were associated with disease severity or response to antidepressant treatment, suggesting a potential role in patient stratification. However, current evidence does not support their routine use in clinical settings. Further research is needed to clarify their specificity and predictive value in psychiatric populations. Once validated, these markers may help identify inflammation-related depression subtypes and guide more precise treatment strategies.