Fig. 3

Overlap of miRNA in the microbiome, CHD, and EBD. Panel a depicts the shared miRNA between cardiac disease and vascular development and the microbiome. These would be targets for study to evaluate links and similar mechanisms of action. Panel b demonstrates potential regulatory mechanisms of miRNA on cardiac and vascular function, intestinal epithelium, and the microbiome in CHD. MiR-1226-5p regulates growth of Fusobacterium nucleatum and miR-515-5p regulates growth of Escherichia coli. Hypoxia from CHD leads to activated HIF-1α, which in turn activates miR-320a. Hypoxia also leads to increased TNF-α which increases miRNA 191a and subsequent disruption of zonula occludens-1, an integral epithelial tight junction protein. Disruption of tight junction proteins leads to intestinal EBD. Hypoxia acts in the heart through NF-κB activated by increased miR-146b, which results in cardiomyocyte apoptosis. Protective features include over activation of miR-146b and reduced miR-82, which protect cardiomyocytes from apoptosis and cell death. MiRNA, micro ribonucleic acid; CHD, congenital heart disease; EBD, epithelial barrier dysfunction; HIF, hypoxia inducing factor; NF-κB, nuclear activating factor kappa B; IEC, intestinal epithelial cell