Predictive value of plasma zonulin for postoperative Hirschsprung-associated enterocolitis

Hirschsprung's disease (HSCR) is a functional obstruction of the gastrointestinal tract characterized by abdominal distension, constipation, and vomiting. The protein zonulin serves as a biomarker for intestinal permeability. We sought to explore the changes in plasma zonulin levels in patients with HSCR and to assess its predictive role in the development of postoperative Hirschsprung-associated enterocolitis (HAEC).

There are 60 patients with HSCR were recruited for this study, categorized into short-segment disease (S-HSCR) (n=33), long-segment disease (L-HSCR) (n=15), and total colonic aganglionosis (TCA) (n=12). Venous blood samples were taken from all participants before and after pull-through surgery. Plasma concentrations of zonulin were determined using an ELISA. Immunohistochemistry (IHC) analysis was conducted to evaluate the expression of zonula occludens-1 (ZO-1) and occludin in colonic tissues. Hematoxylin and Eosin stained (H&E-stained) sections were used to evaluate the degree of inflammation in the dilated (ganglionic) segment. Postoperative outcomes were assessed through a combination of online questionnaires and telephone interviews. Diagnostic threshold for HAEC was based on clinical symptom sets and the HAEC scoring system developed previously.

Preoperative zonulin levels in patients with TCA were statistically lower than those in patients with S-HSCR (p=0.008) and L-HSCR (p=0.028). The incidence of postoperative HAEC was 16.7%, 57.1%, and 14.3% in TCA, L-HSCR, and S-HSCR groups, respectively. Patients who experienced an increase in plasma zonulin levels of more than 1.5 times those on the first day after surgery had a higher risk of developing HAEC (p=0.005). IHC staining further confirmed decreased expression of ZO-1 and occludin in colonic tissues of patients with HSCR who experienced postoperative HAEC.

Preoperative zonulin levels were lowest in the TCA group. The change in zonulin levels on the first day after surgery can serve as a useful indicator for predicting the risk of postoperative HAEC occurrence.