Fig. 1

Relationship of the microbiome and CHD. CHD results in reduced systemic perfusion and/or hypoxemia to the gut. This can lead to dysbiosis, an alteration in the normal gut flora, and reduced healthy bacteria and increased pro-inflammatory bacteria. These bacteria produce cytokine-like molecules, toxins, and metabolites. The byproducts induce intestinal barrier dysfunction, compromising the barrier integrity and a flux of toxins and cytokines into the systemic circulation. These metabolites lead to increased TMAO, which effects endothelial activation, increased thrombotic risk, altered cardiac contractility, and cardiac fibrosis. Dysbiosis also leads to reduced secondary bile acids, which decrease the inotropy in the heart, and increase circulating cytokines. There is also a reduction in short chain fatty acids, such as butyrate, which yield a reduction in vascular tone, increased gut inflammation leading to a “leaky gut”. Increased nitrogen respiration leads to reductions in nitric oxide, maladaptive pulmonary vasoconstriction and promote further growth of pro-inflammatory bacteria. CHD, congenital heart disease; TMAO, trimethylamine N-oxide; SCFA, short chain fatty acids