One of the most exciting scientific developments in the past decade has been the understanding that gut microbiota profoundly impact human physiology. 1 There are hundreds of chemical conversions performed by bacteria for which humans are lacking the respective enzymes. Selective tools to understand this communication and co-metabolism between the host and the bacteria are of the upmost importance. We have developed a chemical biological technique by combining selective enzymatic cleavage with metabolomics analysis.2 We selectively converted sulfate metabolites, present in urine and feces, detect them by liquid chromatography mass spectrometry (UPLC-MS/MS), and developed identification of selective features using the XCMS platform on R.3 Through this state-of-the-art metabolomics analysis, combined with selective cleavage of sulfate, we were able to detect three times higher number of metabolites than reported in the Human Metabolome Database (HMDB). We also were able to extensively study the enzymatic activity of the newly purified arylsulfatase, with a comprehensive analysis of the substrate specificity, as well as enzyme kinetic properties.4 Furthermore, we applied a similar approach to study glucuronidated molecules and described a new technique to perform compound identification, which is one of the bottlenecks of metabolomics. Application of our recently published metabolite-analyzing methodologies led to the identification of previously unknown metabolites using mass spectrometry-based metabolomics.2,5,6 Furthermore, several of the molecules identified have been correlated with human host co-metabolism, proving the broad applicability of this new analytical tool for further integration to metabolomics studies.

Advanced metabolomics and chemical biology approaches for selective analysis of microbiota and human co-host metabolism

2019 Fall National Meeting

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