Fontan patients have elevated plasma straight and branched SCFAs linked to adverse clinical and hemodynamic profiles; further evaluation is warranted.
Fontan patients exhibited significantly elevated plasma propionic acid levels compared to healthy controls.
Fontan patients had significantly elevated plasma butyric acid levels compared to healthy controls.
Fontan patients had significantly elevated plasma valeric acid and caproic acid levels compared to healthy controls.
Acetic acid levels did not differ significantly between Fontan patients and healthy controls.
Branched-chain SCFAs isobutyric acid and 2-methylbutyric acid were significantly elevated in Fontan patients compared to controls.
Branched-chain SCFAs isobutyric acid and 2-methylbutyric acid were significantly correlated with dehydrolithocholic acid levels in Fontan patients.
Fontan circulation is associated with progressive multisystem dysfunction whose biochemical mechanisms, including gut microbiome-derived metabolite profiles, remain poorly understood.
This research examined whether people living with Fontan circulation — a surgical arrangement used to manage certain congenital heart defects where one side of the heart is underdeveloped — have different levels of gut bacteria-produced chemicals in their blood compared to healthy people. The study measured short-chain fatty acids (SCFAs), which are small molecules made by gut bacteria when they break down food. Twenty Fontan patients and 20 healthy matched controls were compared. The study found that Fontan patients had significantly higher blood levels of several SCFAs, including propionic acid, butyric acid, valeric acid, caproic acid, isobutyric acid, and 2-methylbutyric acid. Only acetic acid levels were similar between the two groups. The elevated branched-chain SCFAs (isobutyric acid and 2-methylbutyric acid) were also linked to higher levels of a secondary bile acid called dehydrolithocholic acid and other bile acid components, suggesting a broader pattern of altered gut-derived metabolites in Fontan patients. Importantly, several of these SCFAs correlated with clinical and hemodynamic (blood flow and heart pressure) measures, suggesting they may be connected to the heart and circulatory problems seen in these patients. This research suggests that the gut microbiome may play a role in the multisystem complications experienced by people with Fontan circulation. The findings point to a distinctive metabolic signature in this population that could potentially serve as a target for future investigation into why Fontan patients develop progressive organ dysfunction. The authors emphasize that further research is needed to understand whether these elevated SCFAs contribute to disease or are a consequence of the altered circulation.
Shah A, Liu Y, Armstrong H, Han J, Goodlett D, Ravandi A, et al.. (2026). Association of Fontan Circulation With Gut Microbiome Derived Straight and Branched Short Chain Fatty Acids.. Journal of gastroenterology and hepatology. https://doi.org/10.1111/jgh.70405