Elevated trimethylamine--oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients with normal liver function.

Background: Trimethylamine--oxide (TMAO) is produced in the liver from trimethylamine, which is exclusively generated by gut bacteria.

Objective: The objective of this article is to investigate the relationship between TMAO and primary sclerosing cholangitis (PSC) and its clinical characteristics.

Methods: Serum TMAO was measured in 305 PSC patients, 90 ulcerative colitis patients and 99 healthy controls.

Results: In PSC patients with normal liver function ( = 197), TMAO was higher in patients reaching liver transplantation or death during follow-up than those who did not, with an optimal TMAO cut-off of 4.1 µM (AUC = 0.64,  < 0.001). PSC patients with high TMAO (>4.1 µM,  = 77) exhibited shorter transplantation-free survival than patients with low TMAO ( = 120, log-rank test:  < 0.0001). High TMAO (>4.1 µM) was associated with reduced transplantation-free survival (HR 1.87,  = 0.011), independently of the Mayo risk score (HR 1.74,  < 0.001). Overall, PSC patients demonstrated reduced TMAO values compared with ulcerative colitis and healthy controls, mainly caused by PSC patients with reduced liver function (INR > 1.2), suggesting impaired oxidation of trimethylamine to TMAO. PSC patients with and without inflammatory bowel disease had similar TMAO levels.

Conclusion: In PSC patients with normal liver function, elevated TMAO was associated with shorter transplantation-free survival, potentially reflecting clinically relevant metabolic changes resulting from dietary interactions with the gut microbiota.