Background: Congenital heart disease (CHD) is the most common birth defect, occurring in roughly 40,000 US births annually. Malnutrition and feeding intolerance (FI) in CHD ranges from 30-42% and is associated with longer hospitalization and increased mortality. Cardiopulmonary bypass (CPB) required for surgical repair of CHD induces a systemic inflammatory response worsening intestinal dysbiosis and inducing intestinal epithelial barrier dysfunction (EBD), possibly contributing to post-operative FI.
Objective: To determine the relationship of post-operative FI with intestinal Microbiome, short-chain fatty acids (SCFA), and EBD in pediatric CHD after cardiac surgery.
Methods: Prospective study of patients aged 0-15 years undergoing cardiac surgery with CPB. Samples were collected pre-operatively and post-operatively to evaluate the gut microbiome, plasma EBD markers, short-chain fatty acids (SCFA), and plasma cytokines. Clinical data was collected to calculate a FI score and evaluate patient status post-operatively.
Results: We enrolled 26 CPB patients and identified FI (n=13). Patients with FI had unique microbial shifts with reduced SCFA-producing organisms, Rothia, Clostridium innocuum, and Intestinimonas. Patients who developed FI had associated elevations in plasma EBD markers, claudin-2 (p<0.05), claudin-3 (p<0.01), and fatty acid binding protein (p<0.01). Patients with FI had reduced plasma and stool SCFAs. Mediation analysis showed the microbiome functional shift was associated with reductions in stool butyric and propionic acid in patients with FI.
Conclusion: We provide novel evidence that intestinal dysbiosis, markers of EBD, and SCFA depletion are associated with FI. This data will help towards identifying mechanism and therapeutics to improve clinical outcomes following pediatric cardiac surgery.
Keywords: Cardiopulmonary Bypass; Congenital Heart Disease; Epithelial Barrier Dysfunction; Feeding Intolerance; Microbiome.