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Abstract

Exploring Gut Microbiota Metabolism—New Chemical Biology Tools for Metabolomics Analysis †

by
Vladyslav Dovhalyuk
1,*,
Amanpreet Kaur
1,
Weifeng Lin
1,
Ioanna Tsiara
1,
Sydney Mwasambu
1 and
Daniel Globisch
1,2,*
1
Department of Chemistry-BMC, Science for Life Laboratory, Uppsala University, 751 23 Uppsala, Sweden
2
Centre for Translational Microbiome Research (CTMR), Karolinska Institute, 171 77 Solna, Sweden
*
Authors to whom correspondence should be addressed.
†
Presented at the International Conference EcoBalt 2023 “Chemicals & Environment”, Tallinn, Estonia, 9–11 October 2023.
Proceedings 2023, 92(1), 64; https://doi.org/10.3390/proceedings2023092064
Published: 29 November 2023
(This article belongs to the Proceedings of International Conference EcoBalt 2023 "Chemicals & Environment")
Versions Notes

The impact of the gut microbiota on human physiology through their vast metabolic activities has surfaced as a remarkable scientific discovery over the past decade. It has provided new avenues for biomarker discovery, especially via the analysis of known and unknown metabolites using mass spectrometry-based metabolomics. In the face of limited tools in chemical biology for metabolomics, we have designed advanced methodologies utilizing ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) [1,2,3,4], with an intent to uncover unknown metabolites from human samples, specifically from pancreatic cancer patients.
Understanding the bioactive metabolites produced by the gut microbiome, especially thiol-containing metabolites, is key to the discovery of potential novel drug scaffolds and dietary or disease biomarkers. To overcome the challenge posed by the lack of specific tools for analyzing thiol-containing metabolites, we have synthesized a unique chemoselective probe coupled to magnetic beads. This facilitates easy extraction of metabolites and enhances the mass spectrometric sensitivity significantly. Application of this technique on fecal samples has unveiled previously unknown metabolites and boosted the detection limit for most metabolites [1,2,3,4].
In a novel approach, we have incorporated bicyclobutane into our methodology for the chemoselective and irreversible capturing of thiol metabolites. Applying this tool to human plasma, fecal samples, and bacterial cultures, we have identified the core bacterial thiol metabolome of 394 features and specific bacterial metabolites for each bacterium, including first-time detections in human plasma [1].
This novel chemical biology method surmounts analytical limitations and simplifies the investigation of bioactive thiol-containing metabolites [1]. It uncovers a host of previously unidentified metabolites from dietary, bacterial, and human origins and paves the way for comprehensive mass spectrometric investigations. This holds significant potential for the discovery of disease biomarkers and therapeutic interventions.

Author Contributions

Conceptualization, D.G.; methodology, V.D., A.K., W.L., I.T. and S.M.; validation, V.D., A.K. and W.L.; formal analysis, V.D., A.K., W.L., I.T. and S.M.; investigation, V.D., A.K. and W.L.; resources, D.G.; data curation, V.D., A.K., W.L., I.T. and S.M.; writing—original draft preparation, V.D.; writing—review and editing, V.D. and D.G.; visualization, V.D., A.K. and W.L.; supervision, D.G.; project administration, D.G.; funding acquisition, D.G. All authors have read and agreed to the published version of the manuscript.

Funding

We are grateful for funding by the Swedish Research Council (VR 2016-04423/VR 2020-04707), the Swedish Cancer Foundation (19 0347 Pj), and the Science for Life Laboratory (SLL 2016/5) to D.G.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

This study made use of the NMR Uppsala infrastructure, which is funded by the Department of Chemistry–BMC and the Disciplinary Domain of Medicine and Pharmacy.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Kaur, A.; Lin, W.; Dovhalyuk, V.; Driutti, L.; Di Martino, M.L.; Vujasinovic, M.; Löhr, J.-M.; Sellin, M.E.; Globisch, D. Chemoselective bicyclobutane-based mass spectrometric detection of biological thiols uncovers human and bacterial metabolites. Chem. Sci. 2023, 14, 5291–5301. [Google Scholar] [CrossRef] [PubMed]
  2. Lin, W.; Conway, L.P.; Vujasinovic, M.; Löhr, J.-M.; Globisch, D. Chemoselective and Highly Sensitive Quantification of Gut Microbiome and Human Metabolites. Angew. Chem. Int. Ed. 2021, 60, 23232–23240. [Google Scholar] [CrossRef] [PubMed]
  3. Garg, N.; Conway, L.P.; Ballet, C.; Correia, M.S.; Olsson, F.K.; Vujasinovic, M.; Löhr, J.-M.; Globisch, D. Chemoselective Probe Containing a Unique Bioorthogonal Cleavage Site for Investigation of Gut Microbiota Metabolism. Angew. Chem. Int. Ed. 2018, 57, 13805–13809. [Google Scholar] [CrossRef] [PubMed]
  4. Conway, L.P.; Garg, N.; Lin, W.; Vujasinovic, M.; Löhr, J.-M.; Globisch, D. Chemoselective probe for detailed analysis of ketones and aldehydes produced by gut microbiota in human samples. Chem. Commun. 2019, 55, 9080–9083. [Google Scholar] [CrossRef] [PubMed]
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Share and Cite

MDPI and ACS Style

Dovhalyuk, V.; Kaur, A.; Lin, W.; Tsiara, I.; Mwasambu, S.; Globisch, D. Exploring Gut Microbiota Metabolism—New Chemical Biology Tools for Metabolomics Analysis. Proceedings 2023, 92, 64. https://doi.org/10.3390/proceedings2023092064

AMA Style

Dovhalyuk V, Kaur A, Lin W, Tsiara I, Mwasambu S, Globisch D. Exploring Gut Microbiota Metabolism—New Chemical Biology Tools for Metabolomics Analysis. Proceedings. 2023; 92(1):64. https://doi.org/10.3390/proceedings2023092064

Chicago/Turabian Style

Dovhalyuk, Vladyslav, Amanpreet Kaur, Weifeng Lin, Ioanna Tsiara, Sydney Mwasambu, and Daniel Globisch. 2023. "Exploring Gut Microbiota Metabolism—New Chemical Biology Tools for Metabolomics Analysis" Proceedings 92, no. 1: 64. https://doi.org/10.3390/proceedings2023092064

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