About this work
We and others have shown that the host diet and gut microbiome combine to produce a range of microbiome-generated plasma metabolites that influence human health. Characterizing these metabolites and their relationships with major disease endpoints in human populations is critical to elucidate new pathways of risk and corresponding novel preventive and pharmacologic treatments. Our prior work on gut microbial trimethylamine N-oxide (TMAO) pathway has demonstrated high impact findings regarding the associations of TMAO metabolites with incident subclinical CVD, clinical cardiovascular events, mortality, and other health outcomes.
The new grant focuses on another novel set of gut microbial metabolites, namely metabolites of aromatic amino acids (AAA). Gut microbial fermentation of AAAs, including phenylalanine, tryptophan, and tyrosine, is an understudied and, based on our preliminary studies, exciting new area of CVD research. Dietary sources of AAAs include beef, pork, chicken, fish, dairy, eggs, and less so, plant proteins.
After ingestion, these AAAs can be metabolized by the gut microbiota into a plethora of small circulating molecules. A limited number of AAA-derived metabolites were previously identified as of potential interest in health, with some (e.g., phenylalanine-derived metabolites PAGln and PAGly, tyrosine-derived metabolite pCS, and tryptophan-derived metabolite IS) showing pro-CVD effects on platelet function and thrombosis in mechanistic studies and associated…
