Webinar - Dissecting the impact of gut microbiome on human health by mass spectrometry-based metabolomics
Title: Dissecting the impact of gut microbiome on human health by mass spectrometry-based metabolomics
Duration: 55 minutes
Available On Demand
In this presentation, we will describe results of new studies1 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.
1Ina Nemet, Prasenjit Saha, Nilaksh Gupta, et al, A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors, Cell, 180 (2020) 862-877.