Bile acid dysregulation in Fontan circulation: A Parallel to hyperglycemia in diabetes?

Survivors of the Fontan circulation increasingly develop late multisystem complications, including liver disease, cardiac dysfunction, and frailty, despite stable hemodynamics. Emerging metabolomic data demonstrate chronically elevated circulating bile acids in Fontan patients, implicating a previously underrecognized metabolic contributor to disease progression. Drawing parallels with diabetes mellitus, in which chronic hyperglycemia drives silent organ injury through metabolic memory, we propose that persistently elevated bile acids act as a similar pathogenic driver in the Fontan circulation. Bile acid–mediated mitochondrial dysfunction, inflammation, and fibrosis may imprint early cellular injury that manifests clinically years later. This framework highlights the potential importance of early bile acid surveillance and timely metabolic intervention to prevent irreversible end-organ damage and improve long-term outcomes in Fontan patients.