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 unknown bioactive molecules and biomarkers as only limited information on this co-metabolism has been elucidated on a molecular level. Mass spectrometry-based metabolomics analysis is the method of choice for the analysis of known and discovery of unknown metabolites. Advanced Chemical Biology tools are still limited in metabolomics compared to other ‘omics research fields. Especially, the detailed and selective analysis of microbial metabolism remains a major challenge that requires specific techniques. To overcome limitations in metabolomics analysis, we have developed new state-of-the-art Chemical Biology methodologies for that exceed the scope of global metabolomics analysis.[2-7] These unique metabolite analysis tools were applied for the discovery of unknown metabolites in human samples to evaluate their potential as biomarkers. We have developed arylsulfatase-based metabolite analysis methods for specific identification of sulfated metabolites as this compound class represents a signature for microbiome-host co-metabolism.[2-5] This analysis led to identification of more than 230 sulfated metabolites, exceeding the number of this metabolite class in common metabolomics databases. An optimized enzymatic method was applied for a dietary intervention study to investigate the dietary sulfatome (sulfated metabolome), which revealed 11 previsouly unknown dietary markers.[3] Several metabolites identified were correlated with human host and microbiota co-metabolism, demonstrating the broad applicability of this new analytical tool for elucidation of the cross-talk of gut microbes and their host. Based on our interested in phase II modifications, we investigated cell lines from rapid and slow acetylators that led to the identification of a series of unexpected and endogenous substrates for the common human N-acetyltransferase NAT2.[1]

Exploring host-microbiota co-metabolism – Unique enzymatic chemical biology tools for metabolomics analysis

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

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