One of the most exciting scientific developments in the past decade has been the understanding that gut microbiota profoundly impact human physiology. The complex consortium of trillions of microbes possesses a wide range of metabolic activity. This metabolic interspecies communication represents a tremendous opportunity for the discovery of bioactive molecules as only limited information on this co-metabolism exists. Mass spectrometric metabolomics is the method of choice for metabolic investigation due to its sensitivity over several orders of magnitude.[1] Advanced Chemical Biology tools are limited compared to other ‘omics research fields. Especially, the detailed and selective analysis of microbial metabolism remains a major challenge that requires more advanced techniques. We have developed new state-of-the-art Chemical Biology methodologies for an enhanced metabolomics analysis using liquid chromatography-coupled with tandem mass spectrometry (UPLC-MS/MS).[2-6] These unique metabolite-analyzing tools overcome limitations in mass spectrometry-based metabolomics analysis. We utilize these methods for the discovery of unknown metabolites collected from pancreatic cancer patients to evaluate their potential as biomarkers. We have designed a unique chemoselective probe immobilized to magnetic beads that allows for facile extraction of metabolites with increased mass spectrometric sensitivity by six orders of magnitude and led to discovery of unknown microbiome metabolites.[2-4] A new bioorthogonal cleavage site facilitates efficient release of captured metabolite. We also developed an enzyme-based metabolite analysis method for simplified identification of converted sulfated metabolites, which represent a signature for microbiome-host co-metabolism.[5,6] This analysis led to identification of 206 sulfated metabolites, exceeding the number in common metabolomics databases by a factor of three. We have now investigated a dietary intervention study and identified several previously unknown and undetected metabolites that are specifically derived from microbiota metabolism.

Investigation of host-microbiota co-metabolism as a new strategy for biomarker discovery: Unique chemical biology tools for metabolomics analysis

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.