Fig. 4

Hypothesis of the heart-gut axis in congenital heart disease. Flow chart describing the pathogenesis of dysbiosis and the resulting systemic inflammation and end organ changes exacerbating the disease state in CHD. CHD causes reduced cardiac output. This reduced cardiac output leads to less intestinal perfusion and an increase in venous congestion as blood is not being pumped through the system as well. The resulting mucosal inflammation and edema yields an increase in pro-inflammatory growth, a reduction in intestinal barrier function, and increase intestinal permeability often described as a “leaky gut”. This increased permeability leads to an increase in bacterial translocation and further leads to an increase in circulating toxins, such as LPS. The increased pro-inflammatory bacterial growth results in an increase in TMAO production through the liver, and a reduction in SCFA and secondary bile acids which are important for barrier regulation and cardiac health. The pro-inflammatory bacterial also engage in nitrogen respiratory which results in fewer nitric oxide precursors and can exacerbate the maladaptive response of pulmonary hypertension from an increase in pulmonary blood flow. The feedback loops exacerbate the pathology. CHD, congenital heart disease; LPS, lipopolysaccharide; SCFA, short chain fatty acid; TMAO, trimethylamine N-oxide