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Updated: Apr 25, 2026
Testing Epithelial Permeability in Fetal Tissue-Derived Enteroids
Published on: June 16, 2022
Clinical characteristics associated with postoperative intestinal epithelial barrier dysfunction in children with
Katri V Typpo1, Claire B Larmonier, Jendar Deschenes
11Department of Pediatrics and the Steele Children's Research Center, University of Arizona, Tucson, AZ. 2Department of Anesthesia, University of Arizona, Tucson, AZ. 3Department of Immunobiology, University of Arizona, Tucson, AZ.
Insights
Children with congenital heart disease often have preoperative intestinal injury. Increased illness severity, not cardiopulmonary bypass inflammation, impacts late intestinal barrier function post-surgery.
Area of Science:
- Pediatric Cardiology
- Gastroenterology
- Critical Care Medicine
Background:
- Children with congenital heart disease (CHD) exhibit impaired intestinal epithelial barrier function, increasing risks of sepsis and organ dysfunction.
- The impact of cardiopulmonary bypass (CPB) and associated inflammatory responses on intestinal barrier function in these children remains unclear.
Purpose of the Study:
- To investigate changes in plasma biomarkers reflecting intestinal epithelial barrier function (cellular and paracellular) after CPB.
- To assess the relationship between these biomarkers, inflammatory cytokines, and the severity of illness in pediatric ICU patients.
Main Methods:
- Prospective cohort study of 20 children (neonate to 18 years) undergoing CPB for CHD.
- Measured plasma biomarkers: intestinal fatty acid-binding protein (I-FABP), citrulline, claudin 3, and dual sugar permeability.
- Assessed plasma cytokines (IL-6, TNF-α, IFN-γ, IL-4, IL-10) and correlated biomarker levels with ICU care severity.
Main Results:
- All patients had elevated baseline I-FABP. Early changes in I-FABP2 and citrulline correlated with CPB cytokine response.
- Later biomarker changes (claudin 3, I-FABP2, dual sugar ratio) linked to feeding intolerance.
- I-FABP levels correlated with vasoactive-inotrope score; citrulline showed complex relations with illness severity.
Conclusions:
- Children undergoing CPB for CHD are susceptible to intestinal injury, often with preoperative barrier dysfunction.
- Increased illness severity and need for cardiopulmonary support, rather than CPB inflammation, appear to drive late postoperative intestinal barrier impairment.
Objective:
Children with congenital heart disease have loss of intestinal epithelial barrier function, which increases their risk for postoperative sepsis and organ dysfunction. We do not understand how postoperative cardiopulmonary support or the inflammatory response to cardiopulmonary bypass might alter intestinal epithelial barrier function. We examined variation in a panel of plasma biomarkers to reflect intestinal epithelial barrier function (cellular and paracellular) after cardiopulmonary bypass and in response to routine ICU care.
Design:
Prospective cohort.
Setting:
University medical center cardiac ICU.
Patients:
Twenty children aged between newborn and 18 years undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass.
Interventions:
We measured baseline and repeated plasma intestinal fatty acid-binding protein, citrulline, claudin 3, and dual sugar permeability testing to reflect intestinal epithelial integrity, epithelial function, paracellular integrity, and paracellular function, respectively. We measured baseline and repeated plasma proinflammatory (interleukin-6, tumor necrosis factor-α, and interferon-γ) and anti-inflammatory (interleukin-4 and interleukin-10) cytokines, known to modulate intestinal epithelial barrier function in murine models of cardiopulmonary bypass.
Measurements And Main Results:
All patients had abnormal baseline intestinal fatty acid-binding protein concentrations (mean, 3,815.5 pg/mL; normal, 41-336 pg/mL). Cytokine response to cardiopulmonary bypass was associated with early, but not late, changes in plasma concentrations of intestinal fatty acid-binding protein 2 and citrulline. Variation in biomarker concentrations over time was associated with aspects of ICU care indicating greater severity of illness: claudin 3, intestinal fatty acid-binding protein 2, and dual sugar permeability test ratio were associated with symptoms of feeding intolerance (p < 0.05), whereas intestinal fatty acid-binding protein was positively associated with vasoactive-inotrope score (p = 0.04). Citrulline was associated with larger arteriovenous oxygen saturation difference (p = 0.04) and had a complex relationship with vasoactive-inotrope score.
Conclusions:
Children undergoing cardiopulmonary bypass for repair or palliation of congenital heart disease are at risk for intestinal injury and often present with evidence for loss of intestinal epithelial integrity preoperatively. Greater severity of illness requiring increased cardiopulmonary support rather than the inflammatory response to cardiopulmonary bypass seems to mediate late postoperative intestinal epithelial barrier function.
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