Elevation of Gut-Derived p-Cresol During Spaceflight and its Effect on Drug Metabolism and Performance in Astronauts
Year: 2020
Type: preprint
Abstract: Metabolites produced by enteric microbes may have important effects on astronauts on long-duration missions. The NASA Twins Study provided the most comprehensive multi-scale omics data to date from which to extract molecular features of potential clinical significance to spaceflight. From the multivariate data, we identified an elevation of the uremic toxin p -cresol, which is produced by gut microbial fermentation of dietary tyrosine. p -Cresol has adverse metabolic effects via depletion of the hepatic sulfur pool, which impacts metabolism of drugs, endogenous metabolites, and xenobiotics. Moreover, p -cresol reshapes gut microbial community structure by facilitating survival of species such as clostridia and inhibition of butyrate producers. Spaceflight may also impact the genes responsible for the metabolism of p -cresol (e.g. SULT) and for the safe metabolism of common drugs used in space, such as acetaminophen (e.g. SULT, CYP4502E1, GST). Understanding p -cresol production and its related molecular networks in astronauts may lead to precision medicine advances that enhance astronaut safety and performance on long-duration missions.
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: THIS PROPOSAL FOR A TRANSLATIONAL RESEARCH INSTITUTE IS SUBMITTED ON BEHALF OF A CONSORTIUM OF NON-PROFIT ACADEMIC INSTITUTIONS IN RESPONSE TO NASA C, G4592872366, Joan & Sanford I. Weill Medical College of Cornell University - to monitor the spread of antimicrobial resistance by generating a global map of bacterial species, resistance genes and markers, and modified bases..., A REMARKABLE ONCE-IN-A-LIFE TIME OPPORTUNITY CURRENTLY EXITS TO EVALUATE THE EFFECTS OF SPACEFLIGHT FACTORS ON THE MONOZYGOTIC TWIN ASTRONAUTS SCOTT, G7214279088
OpenAlex ID: W3099795002