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Published on: October 21, 2017
Elevated trimethylamine-N-oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients
Martin Kummen1,2,3,4, Mette Vesterhus1,5, Marius Trøseid2,4,6
1Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
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.
Insights
Elevated trimethylamine-N-oxide (TMAO) in primary sclerosing cholangitis (PSC) patients with normal liver function indicates shorter transplant-free survival. This suggests gut microbiota and diet influence PSC progression.
Area of Science:
- Gastroenterology
- Metabolic Medicine
- Microbiome Research
Background:
- Trimethylamine-N-oxide (TMAO) is a metabolite produced by gut bacteria and processed by the liver.
- TMAO levels are influenced by diet and gut microbial activity.
Purpose of the Study:
- To investigate the association between TMAO levels and primary sclerosing cholangitis (PSC).
- To explore the relationship between TMAO and clinical characteristics of PSC, including disease progression and survival.
Main Methods:
- Serum TMAO levels were quantified in 305 PSC patients, 90 ulcerative colitis patients, and 99 healthy controls.
- Transplantation-free survival was analyzed in relation to TMAO levels and clinical factors.
Main Results:
- In PSC patients with normal liver function, higher TMAO levels (>4.1 µM) were significantly associated with reduced transplantation-free survival.
- Elevated TMAO independently predicted shorter survival, even after adjusting for the Mayo risk score.
- PSC patients with impaired liver function showed lower TMAO levels, suggesting reduced trimethylamine oxidation.
Conclusions:
- Elevated TMAO in PSC patients with normal liver function is a potential biomarker for poorer prognosis and shorter transplantation-free survival.
- These findings highlight the interplay between gut microbiota, diet, metabolism, and PSC progression.
- Further research into TMAO's role may offer novel therapeutic targets for PSC.
