Martin Kummen1,2,3,4, Mette Vesterhus1,5, Marius Trøseid2,4,6, Bjørn Moum3,7, Asbjørn Svardal8, Kirsten Muri Boberg1,3,9, Pål Aukrust2,3,4,6, Tom Hemming Karlsen1,2,3,4,9,10, Rolf Kristian Berge8,11, Johannes Roksund Hov1,2,3,4,9. 1. Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. 2. K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway. 3. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 4. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 5. Department of Medicine, National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway. 6. Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway. 7. Division of Medicine, Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway. 8. Department of Clinical Science, University of Bergen, Bergen, Norway. 9. Section of Gastroenterology, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. 10. Department of Clinical Medicine, University of Bergen, Bergen, Norway. 11. Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
Abstract
BACKGROUND: Trimethylamine-N-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 (n = 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, p < 0.001). PSC patients with high TMAO (>4.1 µM, n = 77) exhibited shorter transplantation-free survival than patients with low TMAO (n = 120, log-rank test: p < 0.0001). High TMAO (>4.1 µM) was associated with reduced transplantation-free survival (HR 1.87, p = 0.011), independently of the Mayo risk score (HR 1.74, p < 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.
BACKGROUND:Trimethylamine-N-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 PSCpatients, 90 ulcerative colitispatients and 99 healthy controls. RESULTS: In PSCpatients with normal liver function (n = 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, p < 0.001). PSCpatients with high TMAO (>4.1 µM, n = 77) exhibited shorter transplantation-free survival than patients with low TMAO (n = 120, log-rank test: p < 0.0001). High TMAO (>4.1 µM) was associated with reduced transplantation-free survival (HR 1.87, p = 0.011), independently of the Mayo risk score (HR 1.74, p < 0.001). Overall, PSCpatients demonstrated reduced TMAO values compared with ulcerative colitis and healthy controls, mainly caused by PSCpatients with reduced liver function (INR > 1.2), suggesting impaired oxidation of trimethylamine to TMAO. PSCpatients with and without inflammatory bowel disease had similar TMAO levels. CONCLUSION: In PSCpatients 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.
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