Zdenek Spacil (Presenter)
Masaryk University
Bio: Dr. Spacil has extensive interdisciplinary research experience in analytical chemistry, mass spectrometry, separation science and clinical chemistry. As postdoctoral fellow, Dr. Spacil worked in the research groups of Prof. Frantisek Turecek and Michael H. Gelb at Univ. of Washington. During his scientific career at Univ. of Washington and Institute for Systems Biology, he substantially contributed to The National Institutes of Health NIH/NIDDK funded project (R01 DK 067859-09) entitled “Multiplex Analysis of Inborn Errors of Metabolism” and The Bill and Melinda Gates Foundation Grants (OPP1039684 and OPP1115430). Currently he is a principal investigator (GACR project No. 17-24592Y) at Masaryk University, leading a newly established research group engaged in metabolomics and targeted proteomics and pioneering the exposome (i.e. non genetic factors affecting human health).
Authorship: Zdenek Spacil (1), Tereza Pavlova (1,2), Veronika Vidova (1), Jana Klanova (1)
(1) Faculty of Science, Masaryk University, Brno, Czech Republic (2) Faculty of Medicine, Masaryk University, Brno, Czech Republic
| Short Abstract Environmental factors may trigger diseases and arguably the most important of biotic factors is gut microbiota, directly affecting human health. However, molecular mechanisms underlying the interaction of microbe-derived metabolites with host signaling and metabolic pathways remain to be elucidated. Gut microbiota seems to influence physiological processes in the host, such as energy metabolism, immunomodulation or neurodevelopment. Mass spectrometry-based metabolic profiling was used to determine markers of microbial colonization, immune homeostasis, energy metabolism status and aging in various biological materials. To the best of our knowledge this is the first time metabolic profiling supported with targeted proteomics was used to simultaneously investigate several important pathways and to evaluate concentration levels of biomarkers in diverse biological materials. |
Long Abstract
Introduction
Environmental factors were associated with numerous health outcomes and they are probably pivotal triggers of dreaded diseases such as Alzheimer’s disease, asthma, diabetes or cancer [1]. Microbiota (an ensemble of all symbiotic or pathogenic microorganisms that share human body space) is arguably the most important biotic environmental factor, directly affecting human health [2, 3]. However, molecular mechanisms underlying the interaction of microbe-derived metabolites with host signaling and metabolic pathways remain to be elucidated. As microbiota seems to influence important physiological processes in the host, particularly energy metabolism, immunomodulation or neurodevelopment, significant alterations in levels of metabolic markers in biological material are expected depending of the diversity of microbial colonization.
Methods
Mass spectrometry-based metabolic profiling utilizing ultra-high performance liquid chromatography (UHPLC) platform and selected reaction monitoring (SRM) assays was used to determine markers of microbial colonization, immune homeostasis, energy metabolism status and aging in biological fluids. Specifically, we have built SRM libraries to investigate metabolic markers of tryptophan and bile acids metabolism in samples of urine (n=69), amniotic fluid (n=58), serum (n=48) and umbilical cord blood serum (n=35). In parallel, we have used SRM-based proteomics to assess circulating endogenous markers of immune response and to investigate either beneficial or harmful effects of microbial colonization on the host.
Results
As the result we have developed a robust methodology applicable to research of the microbiota-host co-metabolism. We have determined microbiota modulated metabolites as well as other biomarkers of important physiological processes in various biological materials and we were able to investigate into the flux of these metabolites within the biological fluids. For instance we have correlated concentration levels between serum-amniotic fluid-urine.
Conclusions & Discussion
To the best of our knowledge this is the first time metabolic profiling was used to simultaneously investigate into several important pathways and to evaluate concentration levels in various biological materials from the same individual. The study is pioneering the role of gut microbiota from a new perspective of metabolomics, which may be transformative to the field helping to elucidate the impact of these organisms on host health, but also for harnessing this knowledge to treat disease.
References & Acknowledgements:
This work was supported by the Grant Agency of the Czech Republic (project No. 17-24592Y), CETOCOEN PLUS (The Ministry of Education, Youth and Sports – MEYS, CZ.02.1.01/0.0/0.0/15_003/0000469) and RECETOX research infrastructure (MEYS, LM2015051).
[1] Lichtenstein P. et al. N Engl J Med 343:78–85 (2000).
[2] Wikoff W.R. et al. Proc. Natl. Acad. Sci. U. S. A. 106: 3698–3703 (2009).
[3] Zhang, L. S. & Davies, S. S. Genome Med. 8: 46 (2016).
| Description | Y/N | Source |
| Grants | yes | the Grant Agency of the Czech Republic |
| Salary | yes | Masaryk University |
| Board Member | no | |
| Stock | no | |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | no |