Fontan patients exhibited significantly elevated plasma levels of several short-chain fatty acids compared to healthy controls, including propionic acid (1.84 vs. 1.19 μM; p=0.002).
Observational (n=40)
Do Fontan patients have altered plasma levels of gut microbiome-derived short-chain fatty acids compared to healthy controls?
Fontan patients have elevated plasma straight and branched short-chain fatty acids that correlate with adverse clinical and hemodynamic profiles, suggesting a role for gut microbiome-derived metabolites in Fontan pathophysiology.
Absolute Event Rate: 1.84% vs 1.19%
p-value: p=0.002
BACKGROUND: Fontan circulation is associated with progressive multisystem dysfunction, yet its biochemical mechanisms are poorly understood. Gut microbiota-derived metabolites, particularly short-chain fatty acids (SCFAs) and bile acids, shape cardiovascular health. We previously reported elevated secondary bile acids in Fontan patients, but their SCFA profile remains uncharacterized. MATERIALS AND METHODS: Fontan patients and matched healthy subjects were evaluated by body composition, frailty, cardiopulmonary exercise testing, hemodynamics, and plasma SCFA quantification. RESULTS: Twenty Fontan patients (25.5 years IQR: 22.8-30.3; 35% women) and 20 healthy controls (30.0 years 25.8-34.3; 30% women) were enrolled. Compared to controls, Fontan patients exhibited elevated plasma levels of several SCFAs: propionic acid (1.84 1.45-2.68 vs. 1.19 1.07-1.49 μM; p = 0.002), butyric acid (1.27 0.90-1.71 vs. 0.75 0.52-0.94 μM; p = 0.002), valeric acid (0.25 0.15-0.36 vs. 0.13 0.11-0.16 μM; p < 0.001), and caproic acid (0.44 0.35-0.67 vs. 0.25 0.21-0.39 μM; p < 0.001). Acetic acid levels did not differ significantly between groups. Additionally, branched-chain SCFAs were elevated in Fontan patients: isobutyric acid (0.44 0.32-0.68 vs. 0.26 0.23-0.30 μM; p < 0.001) and 2-methylbutyric acid (0.38 0.27-0.58 vs. 0.19 0.15-0.25 μM; p < 0.001). Notably, caproic, isobutyric, and 2-methylbutyric acids showed strong correlations with key clinical and hemodynamic parameters. Furthermore, isobutyric and 2-methylbutyric acids were significantly correlated with dehydrolithocholic acid levels (R = 0.67 and 0.54, respectively) and other bile acid components. CONCLUSION: Fontan patients have elevated plasma straight and branched SCFAs linked to adverse clinical and hemodynamic profiles; further evaluation is warranted.
Shah et al. (2026) conducted an observational in Fontan circulation (n=40). Fontan circulation vs. Matched healthy subjects was evaluated on Plasma propionic acid level (p=0.002). Fontan patients exhibited significantly elevated plasma levels of several short-chain fatty acids compared to healthy controls, including propionic acid (1.84 vs. 1.19 μM; p=0.002).