Serum biomarkers of intestinal barrier dysfunction predict postoperative endoscopic recurrence in Crohn’s disease patients

Endoscopy is the primary method for assessing intestinal mucosal inflammation in postoperative Crohn’s disease (CD) patients, but it is invasive. The aim of this study was to investigate the correlation between intestinal barrier permeability plasma biomarkers, including serum diamine oxidase (DAO), D-lactate (D-LA), and endotoxin (ETX), and endoscopic findings in patients who underwent ileocolonic resection for CD and to assess their predictive efficacy. This retrospective cohort study (May 2022 to January 2024) included postoperative CD patients who had undergone ileocolonic resection and met other predefined criteria. Postoperative endoscopic recurrence was assessed via the Rutgeerts score (i0-i1: remission; i2-i4: active). Associations between serum biomarkers and endoscopic disease activity were analyzed, and diagnostic accuracy was assessed via receiver operating characteristic (ROC) curve analysis. A multivariable logistic regression model was used to identify independent predictors, and Decision Curve Analysis (DCA) was performed to evaluate the clinical utility of the final model. There were 153 CD patients in our study, including 72 in the postoperative endoscopic remission group and 81 in the active group, based on the Rutgeerts score. Compared with those in the remission group, D-LA and ETX were significantly elevated in the active group (P < 0.001), whereas DAO levels showed no significant difference. ETX levels were positively correlated with endoscopic disease activity (r = 0.404, P < 0.001), similar to that of fecal calprotectin (FC), and were higher than that of C-reactive protein (CRP) and D-LA. ROC analysis revealed that ETX (AUC = 0.729) outperformed D-LA (AUC = 0.703) and CRP (AUC = 0.657). A combined panel of D-LA, ETX, CRP, and FC demonstrated a high predictive accuracy (AUC = 0.862, sensitivity 82.7%, specificity 77.8%), which was significantly better than that of FC alone (ΔAUC = 0.109, P = 0.001). Multivariable logistic regression confirmed D-LA, ETX, FC, CRP, and smoking history as independent predictors of recurrence. The intestinal barrier biomarkers D-LA and ETX may have the potential to serve as supplementary screening indicators for postoperative endoscopic recurrence in patients with CD, especially when combined with CRP and FC. However, because external validation is lacking, the proposed cutoffs and model should be considered exploratory and require prospective, multi-center external validation and calibration before clinical implementation.