The Prognostic Value of Endotoxemia and Intestinal Barrier Biomarker ZO-1 in Bacteremic Sepsis

Background: Intestinal barrier dysfunction exerts a pivotal pathophysiological role in the development of multiple organ dysfunction in sepsis. The present study was undertaken to investigate the potential role of serum intestinal fatty acid-binding protein (I-FABP) and zonula occludens-1 (ZO-1) levels as biomarkers of intestinal barrier dysfunction in bacteremic sepsis.

Methods: Seventy-five patients with bacteremic sepsis of abdominal origin (n = 34) or nonabdominal origin (n = 41) and 12 healthy controls were retrospectively studied. Blood samples collected upon sepsis diagnosis were analyzed for serum ZO-1, I-FABP and endotoxin levels. Prognostic scores Sequential Organ Failure Assessment (SOFA), quickSOFA and Acute Physiology and Chronic Health Evaluation (APACHE-II) were determined over the first 24 hours after sepsis diagnosis and patients' outcome in terms of 28-day mortality was recorded.

Results: Serum ZO-1 levels were significantly higher in bacteremic septic patients as compared to controls with no difference between patients with abdominal or extra-abdominal source of infection. Serum I-FABP levels were significantly lower in septic patients as compared to control and this reduction was more evident in patients with bacteremic abdominal sepsis. Serum ZO-1 and endotoxin concentrations were found significantly higher in patients who did not survive from sepsis. In receiver operating characteristic curve analysis, both endotoxin and ZO-1 predicted 28-day mortality. In addition, ZO-1 and endotoxin were correlated with the prognostic scores of qSOFA, SOFA and APACHE II.

Conclusions: The results of this study indicate that serum ZO-1 might be a reliable biomarker of gut barrier dysfunction in sepsis, not affected by the abdominal or extra-abdominal site of infection. ZO-1, measured early at sepsis diagnosis, might represent a valuable additional prognostic tool for patients' outcome.