Alteration in Indole Metabolites After Cardiopulmonary Bypass Surgery in Neonates and Infants

Cardiopulmonary bypass (CPB) surgery is associated with changes in the intestinal microbiome. Metabolism of tryptophan into the indole pathway is entirely facilitated by the intestinal microbiome, and indole metabolites play a critical role in intestinal epithelial integrity, intestinal and systemic vascular tone, and intestinal and systemic immune response.

To evaluate the impact of CPB on microbial-derived indole metabolites and their association with clinical outcomes.

Prospective cohort study of neonates and infants younger than 6 months of age undergoing CPB at a quaternary children's hospital.

Serum samples underwent quantitative pathway mapping via mass spectroscopy. Clinical outcomes of interest included cardiac ICU (CICU) length of stay and Vasoactive-Inotropic Score (VIS) at 48 hours.

Ninety patients between 2 and 169 days old were enrolled. Patients showed significant postoperative changes in seven of eight indole metabolites. A two-fold increase in preoperative levels of indole-3-carboxylic acid was associated with 0.63 odds of requiring vasoactive medications at 48 hours (p = 0.023) and among those subjects still requiring vasoactives at 48 hours, they had an average 7.1% decrease in VIS at 48 hours (p = 0.005), and a 12.25% reduction in CICU length of stay (p = 0.001). Higher levels of indole-3-carboxylic acid preoperatively and at 24 and 48 hours postoperatively were also significantly associated with decreased CICU length of stay. Conversely, increased levels of several metabolites, including indole-3-lactic acid, indole-3-carbaldhyde, indole-3-propionic acid, tryptamine, and tryptophol, in the preoperative and postoperative period were associated with higher VIS at 48 hours and increased CICU length of stay.

CPB was associated with significant changes in indole metabolite levels postoperatively. Indole-3-carboxylic acid, which suppresses T-regulatory (Treg) differentiation, is associated with improved patient outcomes, whereas other metabolites, that promote Treg differentiation, were associated with worse outcomes.