Human environmental exposures and corresponding metabolic responses are highly variable, and may contribute to disease in genetically susceptible individuals. Recently, ultra-high resolution mass spectrometry (HRMS) has allowed precise detection of over 50,000 signals, revolutionizing the ability to measure biologic responses (metabolomics) to cumulative exposures such as environmental toxicants, diet, drugs and the microbiome (exposomics). This pilot study involved 80 patients with Primary Sclerosing Cholangitis [PSC] (half of whom had inflammatory bowel disease [IBD]), 40 patients with primary biliary cholangitis [PBC], another cholestatic liver disease, and matched-controls without liver disease (40 for PSC and 40 for PBC). We found unique exposomics and metabolomics between PSC, PBC and controls. The top exposomic association for PSC was a fungicide and for PBC was a surfactant (agent used in many household products including detergents, paints and dyes). The top pathway altered in both diseases involved bile acid metabolism. Using network modelling, we demonstrated that the presence of certain exposomic features seemed to be linked to changes in metabolism. While further studies are needed to understand the relationship between exposures and their effects on the human body, and how these may be linked to disease, this is the first study to use these methods in human samples, and provides a framework with which to study the crucial ways the environment may be involved in the development of disease.
This novel work was selected for an oral presentation in the Presidential Plenary Session (Translational) of the AASLD meeting in San Francisco (November 2018) and it was delivered by Dr. Angela Cheung. The study was supported by the Chris M. Carlos and Catharine Nicole Jockisch Carlos Endowment Fund in PSC and the NIDDK (RO1 DK 80670, RO1 DK 84960 and RC2 DK 118619 to Dr. K. Lazaridis).
View Dr. Cheung's PowerPoint: High-resolution metabolomics and exposomics in PSC and PBC uncovers novel, disease-specific associations in bile acid and amino acid metabolism and environmental toxicant exposures.
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