MSACL 2025 Abstract

Chemical Metabolomics – Innovative Chemical Biology Approaches to Investigate Gut Microbiome Metabolism

Wawrzyniec Haberek, Alejandro Torregrosa Chinillach, Leo Martin, Weifeng Lin, Ioanna Tsiara, Vladyslav Dovhalyuk, Efstathia Vouzaxaki, Daniel Globisch
Department of Chemistry, Uppsala University, Uppsala, Sweden

Wawrzyniec Haberek (Presenter) Uppsala University >> POSTER (PDF)

Relevant Financial Disclosures (within past 24 months, reported on Sep 02, 2025) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

INTRODUCTION:
The metabolism of the gut microbiota plays a critical role in shaping human physiology. Disruptions in this metabolic network have been associated with the onset and progression of various diseases. Despite its significance, the metabolic interactions between host and microbiome remain underexplored. Mass spectrometry (MS) is the gold standard for analyzing microbiome-derived metabolites due to its ability to resolve complex biological matrices such as plasma, feces, and urine. Profiling microbial metabolites holds promise for the discovery of novel bioactive compounds, disease biomarkers, and deeper insights into pathophysiological mechanisms.

OBJECTIVES:
A major limitation in MS-based metabolomics is the poor ionization efficiency of certain metabolite classes. This challenge underlines the need for new methodologies that enhance detection and broaden metabolite coverage. Our objective is to develop innovative chemical biology tools capable of identifying previously undetectable metabolites.

METHODS:
We have developed a suite of chemoselective probes tailored to derivatize specific functional groups of metabolites. These probes are combined with 13C/12C isotope labeling, enabling accurate quantification and comparative analysis. This platform, termed quantitative Sensitive CHEmoselective MetAbolomics (quant-SCHEMA), incorporates magnetic bead-assisted extraction for targeted isolation of metabolite classes. The method is compatible with various biological sample types and significantly enhances MS sensitivity, enabling detection of metabolites at attomole levels.

RESULTS:
Our chemoselective strategies enable the targeted analysis of several metabolite classes, including carbonyls, thiols, amines, and carboxylic acids. Using these tools, we confirmed the presence of clinically relevant, microbiota-derived metabolites in human samples. In a dietary intervention study involving 156 samples, we identified four novel food-derived biomarkers. These findings validate the robustness of our approach. We are now integrating quant-SCHEMA with standard metabolomics workflows in neuroscience, microbiome research, and biomarker discovery.

CONCLUSION:
We have successfully developed and implemented a powerful set of chemoselective tools for exploring host–microbiome metabolic interactions. To date, our work has led to the identification of over 300 previously unknown metabolites, the majority of which originate from gut microbial metabolism. Current efforts focus on characterizing the biological activity and functional roles of these newly discovered compounds

RERERENCES:
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