= Emerging. More than 5 years before clinical availability. (19.79%)
= Expected to be clinically available in 1 to 4 years. (37.97%)
= Clinically available now. (42.25%)
MSACL 2022 : Globisch

MSACL 2022 Abstract

Self-Classified Topic Area(s): Metabolomics

Podium Presentation in De Anza 1 on Thursday at 14:20 (Chair: Jeff Whitman)

Unique Chemical Biology Tools for Metabolomics Analysis – Exploring Gut Microbiota Metabolism

Mario SP Correia, Weifeng Lin, Theodosia Vallianatou, Amanpreet Kaur, Ioanna Tsiara, Sydney Mwasambu, Vladyslav Dovhalyuk, Daniel Globisch
Uppsala University, Sweden

Daniel Globisch (Presenter)
Uppsala University

Presenter Bio: Daniel Globisch studied Chemistry at the Technical University of Kaiserslautern (Germany) and the University of Southern Denmark, Odense (Denmark). He received his Ph.D. from the Ludwig-Maximilians-University Munich (Germany) with Professor Thomas Carell in 2011 and joined the laboratory of Professor Kim D. Janda at The Scripps Research Institute (CA, USA) for his postdoctoral studies. He started his independent career in 2015 at Uppsala University (Sweden) as a Science For Life Laboratory Fellow and was appointed as Associate Professor in 2017. He received tenure in December 2020. Daniel has been elected as a board member of the Nordic Metabolomics Society and is an Editorial Board Member for the metabolomics society journal Metabolites. The interdisciplinary nature of the research projects is focused on the elucidation of the metabolic interaction between the gut microbiota and their human host. His laboratory develops new Chemical Biology tools to extend the scope of metabolomics research for discovery of unknown biomarkers and bioactive metabolites.

Abstract

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 biomarker discovery as only limited information on this co-metabolism has been elucidated on a molecular level.
The detailed investigation of metabolites in any type of human samples has been termed metabolomics and holds a great potential for the discovery of unknown biomarkers and bioactive metabolites. Mass spectrometric analysis is the method of choice for metabolic investigation due to its sensitivity to metabolites over several orders of magnitude. Global metabolomics is the newest ‘omics-research field, for which advanced chemical tools are limited compared to other ‘omics research fields such as transcriptomics and proteomics. Especially, the detailed and selective analysis of microbial metabolism remains a major challenge that requires more advanced techniques due to low metabolite concentrations.

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).[1-5] These unique metabolite-analyzing tools are aimed at overcoming limitations in mass spectrometry-based metabolomics analysis and are selective for microbiome metabolism. We are applying these methods for the discovery of unknown metabolites in human samples collected from pancreatic cancer patients to evaluate their potential as biomarkers.

Chemoselective probes for increased mass spectrometric sensitivity

We have designed and synthesized a unique chemoselective probe immobilized to magnetic beads that allows for facile extraction of metabolites and led to increased mass spectrometric sensitivity by six orders of magnitude.[1,2] An incorporated bioorthogonal cleavage site, which we have adapted from a protecting group that is labile under mild, palladium-catalyzed conditions facilitates efficient release of captured metabolite without altering their chemical structure. This method is available for quantitative and qualitative analysis and was utilized on fecal, plasma and urine samples. Analysis revealed previously unknown metabolites and due to conjugation of the mass-spectrometric tag and separation from the sample background the detection limit for most metabolites was increased by up to a factor of one million. The quantitative method quant-SCHEMA has been developed for direct comparison of different samples towards biomarker discovery.

Selective investigation of human host and microbiota co-metabolism

We also utilized selective enzymatic treatment of metabolites in human samples for simplified identification of converted sulfated and glucuronidated metabolites to elucidate their chemical structure using mass spectrometry.[3,4] Analysis of pretreated samples using ultra high-performance liquid chromatography-mass spectrometric techniques led to the identification of 206 sulfated metabolites, exceeding the number of sulfated metabolites in metabolomics databases by a factor of three to four. We have now investigated the sulfatome in a dietary intervention studies. Many of these identified phase II clearance products are linked to microbiota-human host co-metabolism.

References
[1] W. Lin, …, D. Globisch Angew. Chem. Int. Ed. 2021, 60, 23232–23240.
[2] N. Garg, L.P. Conway, …, D. Globisch Angew. Chem. Int. Ed. 2018, 57, 13805–13809.
[3] C. Ballet, M.S.P. Correia, …, D. Globisch Chem. Sci. 2018, 9, 6233–6239.
[4] M.S.P. Correia, A. Jain, …, D. Globisch Free Radic. Biol. Med. 2020, 160, 745-754.
[5] L.P. Conway, V. Rendo, …, D. Globisch Angew. Chem. Int. Ed. 2020, 59, 14342-14346.


Financial Disclosure

DescriptionY/NSource
Grantsno
Salaryno
Board Memberno
Stockno
Expensesno
IP Royaltyno

Planning to mention or discuss specific products or technology of the company(ies) listed above:

no