The human urinary excretion of trimethylsulfonium

Trimethylsulfonium is a sulfur metabolite found in humans. Little is known about the origin of trimethylsulfonium production and the factors that determine its levels in biological fluids. The aim of the present project is to investigate several aspects that are likely linked to the production of trimethylsulfonium in humans. This investigation is meant to shed light on the contribution of a variety of factors to the production of this metabolite and its significance. Experiments will involve human samples and trimethylsulfonium will be measured using high performance liquid chromatography with tandem mass spectrometric detection . The study is expected to provide us with a better understanding of the production and significance of trimethylsulfonium.

Trimethylsulfonium is a newly discovered sulfur metabolite in humans that we previously hypothesized to be linked with hydrogen sulfide, a gaseous signaling molecule with emerging roles in human health. In this project, we showed that indeed trimethylsulfonium is elevated in down's syndrome, a clinical condition where hydrogen sulfide is known to be overproduced. This supports the possible utility of trimethylsulfonium as a biomarker for hydrogen sulfide. When interpreting the levels of trimethylsulfonium however we showed using a series of studies that genetic factors must be considered as we highlighted the intra-individual and inter-individual variability in the urinary excretion of this metabolite in healthy volunteers. This included a study where we were able to pinpoint genetic variants in the INMT gene which are responsible for the varrying levels of trimethylsulfonium amon humans. These genetic variants have different frequencies among the different ethnic groups and the variable excretion of trimethylsulfonium in 4 different ethnic groups was indeed accordingly established. Furthermore, we investigated the production of trimethylsulfonium and other methylated sulfur metabolites in a group of oil refinery workers occupationally with possible exposure to hydrogen sulfide in air and found elevated levels of the related metabolite dimethylsulfoxide. Finally, we identified a new metabolite in humans, allyl dimethyl sulfonium, which we proposed to be produced through a similar biosynthetic pathway to that of trimethylsulfonium. This metabolite was found to be produced in respose to consumption of sulfur rich food such as garlic and contributes the variable response in body odor to the consumption of this food. Trimethylsulfonium was also elevated in response to this dietary intake which highlights another source of its origin in humans. Overall, the project showed several lines of evidence that trimethylsulfonium may be relevant as a biomarker in humans. We now have better understanding of the urinary excretion of this metabolite in humans and future work will possible involve a deeper investigation of the utility of trimethylsulfonium in specific health conditions and the genetic aspects for its production.