Clinical Implications of Intestinal Barrier Damage in Psoriasis

BACKGROUND: An increasing amount of evidence suggests an association between increased intestinal permeability and the pathogenesis of chronic inflammatory diseases. However, the clinical significance of gut barrier dysfunction in psoriasis remains to be established. OBJECTIVE: To evaluate whether there are differences in disease activity, the severity of gastrointestinal symptoms and the blood concentration of bacterial metabolites in psoriatic patients with a normal and altered intestinal barrier. PATIENTS AND METHODS: Gut barrier integrity was assessed with the serum concentrations of claudin-3, a modulator of intestinal tight junctions and an intestinal fatty acid-binding protein, a marker of enterocyte damage. Gastrointestinal symptoms were evaluated with a validated questionnaire. The concentration of trimethylamine N-oxide (TMAO), a gut microbiota-associated metabolite, was measured with high-performance liquid chromatography. RESULTS: One hundred and fourteen patients with psoriasis were finally enrolled in the study – 68 with an altered gut barrier and 46 with a properly functioning intestinal barrier. Patients with an altered gut barrier showed a significantly higher score in the Gastrointestinal Symptom Rating Scale (3.20 vs 1.46, p<0.001). Moreover, patients with psoriasis and a disrupted intestinal barrier demonstrated a higher disease activity (PASI: 19.7 vs 10.3, p<0.001) and systemic inflammatory parameters (neutrophil-to-lymphocyte ratio: 2.86 vs 1.71, p<0.001; C-reactive protein 3.76 vs 1.92; p<0.05). The marker of bacterial translocation was significantly higher in psoriatic patients with damaged gut integrity (TMAO: 375.7±51.9 vs 119.4±27.5 ng/mL; p<0.05). CONCLUSION: The altered gut barrier in psoriasis is associated with gastrointestinal symptoms, systemic inflammatory profile and the increased blood concentration of gut microbiota-derived metabolite – TMAO. Intestinal barrier modulation represents a new promising therapeutic approach.