Dysbiosis and Intestinal Barrier Dysfunction in Pediatric Congenital Heart Disease is Exacerbated Following Cardiopulmonary Bypass

To map the microbiome and intestinal barrier function in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. The intestinal microbiome is proving integral in health and homeostasis. Systemic inflammation can reduce diversity and increase pro-inflammatory bacteria in the microbiome. These changes disrupt the intestinal barrier and extend cytokine-mediated systemic injury. Patients receiving cardiopulmonary bypass secrete cytokines and have clinical features similar to other forms of systemic inflammation. We hypothesize surgery with bypass results in intestinal dysbiosis and is associated with increased pro-inflammatory bacteria.Prospective study of patients aged 1 month to 18 years assigned in two arms: surgery with bypass and surgery without comparison group. Stool was collected before surgery and 3-5 days after surgery. Stool DNA was extracted and sequenced for microbiome evaluation. Markers of intestinal barrier dysfunction were measured before and after surgery to evaluate intestinal barrier function. 29 patients were enrolled. At baseline, patients with bypass (n=17) had significantly more pro-inflammatory bacteria, Proteobacteria (p<0.001), and reduced healthy Bacteroidetes (p=0.004). Bypass further increased Proteobacteria from 17% to 27%. Beta diversity showed significant changes in pre- and post-surgery between the bypass group compared to controls (n=12; p<0.001). The bypass group also had significantly increased markers of intestinal barrier dysfunction, FABP2 (p=0.001), claudin-3 (<0.0001), and citrulline (p=0.001). Our study offers novel evidence of baseline dysbiosis in congenital heart disease, with bypass further exacerbating dysbiosis and intestinal barrier dysfunction to potentially contribute to morbidity. These results open the door to evaluating therapeutic interventions to improve outcomes.