Clinically Relevant Metabolites of the Human Gut Microbiota
Veronika Vidová, Gabriela Dovrtělová, Kateřina Coufalíková, Eliška Stuchlíková, Anne-Christine Aust, Jana Klanová, Zdeněk Spáčil Masaryk University, the RECETOX Centre
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Zdenek Spacil (Presenter) Masaryk University
Presenter Bio: Dr. Spacil holds a dual doctoral degree in analytical chemistry awarded from both Stockholm University and Charles University in Prague. As a postdoctoral fellow at Univ. of Washington, he introduced modern separation methods (i.e. UHPLC) to newborn screening for lysosomal storage disorders and developed 9-plex assay in dried blood samples. His contribution resulted in several landmark publications and patent applications. Later, Dr. Spacil joined the Institute for Systems Biology (ISB) to take up challenges of targeted proteomics. He is assistant professor, principal investigator and the head of Metabolomics and targeted proteomics core at Masaryk University. His research focuses on the functional characterization of human gut microbiota and aging-induced modulations to the metabolism and immune system, pioneering the broader concept of Exposome (non-genetic influence on human health).
Relevant Financial Disclosures
(within past 24 months)
No relevant financial relationship(s) to disclose.
Abstract
INTRODUCTION: The human gut microbiota represents a pivotal environmental influence on the metabolism and overall health of the host. The immunomodulatory function of microbiota is mediated via the interaction of microbial metabolites with xenobiotic receptors expressed in immune cells and tissues. For instance, microbial catabolites of aromatic amino acids (i.e. tryptophan and tyrosine) were reported to activate pregnane X receptor (PXR) or aryl hydrocarbon receptor (AHR) in a ligand-specific fashion. The immune-metabolic homeostasis may be explored using quantitative metabolic profiling and targeted protein assays.
OBJECTIVES: The primary objective of this study was to determine the potential of specific microbial metabolites and inflammatory proteins as clinically relevant markers of pathology.
METHODS: Tandem mass spectrometry (MS/MS) assays were applied to biofluids and stool swabs using a triple quadrupole mass analyzer (selected reaction monitoring – SRM) for metabolic profiling of tryptophan, kynurenine and tyrosine pathways. SRM-proteomics assays were used for absolute quantification of inflammatory and immunological markers. The untargeted metabolic screening was performed using a high resolution/accurate mass (HR/AM) platform (Orbitrap Fusion, Thermo Scientific).
RESULTS: We have mapped the distribution of microbiota-associated metabolites within biofluids in adults, pregnant women, and neonates and linked them to levels of acute phase proteins. For instance, metabolites of human gut microbiota were quantitatively profiled in preterm premature rupture of the membranes pregnancies. Microbial indolepropionate was determined a reliable marker of adverse intra-amniotic conditions such as microbial-invasion of the amniotic cavity (MIAC). Next, we profiled microbial catabolites and inflammatory proteins in dried blood spots (DBS) and meconium/first stool swabs from neonates to establish signatures for microbial colonization acquired via vaginal delivery in comparison to Cesarean section.
CONCLUSION: The study has identified several metabolites produced by human gut microbiota as clinically relevant markers of dysbiosis or pathology. The functional characterization of microbiota is essential to understanding its role in immune homeostasis and human health.
ACKNOWLEDGMENT
This work was funded by the Grant Agency of the Czech Republic (project No. 17-24592Y), The Grant Agency of the Masaryk University (project No. MUNI/G/1131/2017), CETOCOEN PLUS (Ministry of Education, Youth and Sports e MEYS), (CZ.02.1.01/0.0/0.0/15_003/ 0000469) and by the RECETOX research infrastructure (MEYS), (LM2015051 and CZ.02.1.01/0.0/0.0/16_013/0001761).
= Discovery stage.
= Translation stage.
= Clinically available.
