Dissecting the impact of gut microbiome on human health by mass spectrometry-based metabolomics

In this presentation, we will describe results of new studies(*) employing a combination of untargeted and targeted metabolomic analyses and functional studies to discover and characterize a new gut microbiota dependent pathway mechanistically linked to the development of cardiovascular disease.

Using an initial Learning Cohort of fasting plasma samples from subjects undergoing elective diagnostic cardiac evaluations (n=1,162), analytes whose levels appeared to be associated with incident cardiovascular disease (CVD) risks were identified. Following structural characterization and validation using an independent Validation Cohort (n=4,000) with stable isotope dilution LC/MS/MS analyses, a gut microbiota dependent metabolite was confirmed, and then in animal model studies shown to recapitulate CVD relevant phenotypes in vivo. Microbial bioinformatics studies, genetic engineering (both gain and loss of function) and microbiota transplantation studies confirm a mechanistic link with CVD pathogenesis. And genetic and pharmacological functional studies in rodent models confirmed that the new metabolites interacts with specific GPCRs functionally linked to numerous cardiovascular phenotypes and disorders. The presentation will thus further describe how gut microbiota are mechanistically linked to cardiovascular disease susceptibility, and represent a novel potential therapeutic target for the treatment and prevention of disease.

Presenter: Ina Nemet, Ph.D. (Project Scientist, Cleveland Clinic Foundation)

Ina Nemet is a Project Scientist in the Department of Cardiovascular & Metabolic Sciences at the Cleveland Clinic Lerner Research Institute and an Assistant Professor at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve, Cleveland, OH.

Ina completed her undergraduate studies in biochemical engineering at the School of Food Technology and Biotechnology at the University of Zagreb, Croatia and her PhD in organic chemistry at the School of Science at the same University. She received her postdoctoral training in the Department of Pathology and Department of Pharmacology at Case Western Reserve University, Cleveland, OH.

By using untargeted and targeted metabolomic approaches, she is working on identifying pathways contributing to the development of human diseases with a particular focus on gut microbial derived metabolites and their impact on the host.

During her career, Ina has published 5 book chapters and 33 papers in peer-reviewed journals including two this year as a first and co-first and corresponding author in Cell and the Journal of Lipid research, respectively. She also received multiple awards including a Fulbright Visiting Research Fellowship and a Juvenile Diabetes Research International Postdoctoral Fellowship.

Presenter: Heather Juzwa (Senior Field Sales Engineer, Shimadzu)

Heather Juzwais aSeniorField Sales Engineer at Shimadzu Scientific Instruments and has been since October of 2006. Shegraduated from the University of Pittsburgh in 2000with an honorsbachelors’degree in Chemistry.Having a passion for instrumentation,she washired byHitachi Instrumentsupon graduation.Heather has also held a positionatDigilab, a division of Bio-Rad, which was subsequently purchased by Varian.Heather’s service to the field of chemistry began as an undergraduate and has continued throughout her career.She served as the Secretary of theAmerican Chemical Society – Student Affiliateswhile a senior at the University of Pittsburgh and has remained in theACSsince then.She served as Chair of the Pittsburgh Section in 2011 andcurrently serves as Webmaster for the Pittsburgh Section websiteand has since 2012.Heather’sdirectionpavedthe way for the section to receive an esteemedChemLuminaryfor being anOutstanding Large Local Section for 2012.Heather also servedas Chair of the Society for Analytical Chemists of Pittsburgh in 2013-2014.For many years, she has happily served on and chaired many committees of the Society for Analytical Chemists of Pittsburgh, the Spectroscopy Society of Pittsburgh, and the Pittcon committee and looks forward to playing key roles in these organizations for years to come.Heatherserved astheGeneralChair of the Central Regional Meetingof the ACSinPittsburgh in October 2014. Herleadershipresulted in anotherChemLuminaryfrom the National ACS for Best Regional Meeting.Heather has been a Director ofthe Pittsburgh Local Section of the ACS since 2013.Heather iscurrently serving as Pittcon 2021Treasurer. She won the Distinguished Service Award from the Pittsburgh Local Section of the ACS in 2014 as well as the 2015RegionalE. AnnNalleyRegional Award for Volunteer Service to theentire Central RegionAmerican Chemical Society.With herMay 2020nomination to serve as Chair of the Spectroscopy Society of Pittsburgh for the 2021-2022 year, she became only the fourth person and first woman history to lead all three major scientific organizations in Pittsburgh.

(*) Ina Nemet, Prasenjit Saha, Nilaksh Gupta, et al, A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors, Cell, 180 (2020) 862-877.