biostudies-literatureJamshidi NNational Center for Advancing Translational SciencesNCATS NIH HHSNIDDK NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesNIGMS NIH HHS18308https://www.ebi.ac.uk/biostudies/studies/S-EPMC9622871biostudies-literatureUnknown12(1)In vitro and in vivo studies have established the organic anion transporters OAT1 (SLC22A6, NKT) and OAT3 (SLC22A8) among the main multi-specific "drug" transporters. They also transport numerous endogenous metabolites, raising the possibility of drug-metabolite interactions (DMI). To help understand the role of these drug transporters on metabolism across scales ranging from organ systems to organelles, a formal multi-scale analysis was performed. Metabolic network reconstructions of the omics-alterations resulting from Oat1 and Oat3 gene knockouts revealed links between the microbiome and human metabolism including reactions involving small organic molecules such as dihydroxyacetone, alanine, xanthine, and p-cresol-key metabolites in independent pathways. Interestingly, pairwise organ-orScientific reportsDrug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions.PMC9622871R01GM132938KL2TR001882KL2 TR001882R01 DK109392R01DK109392R01 GM132938Jamshidi NNigam SKfalseDrug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions.In vitro and in vivo studies have established the organic anion transporters OAT1 (SLC22A6, NKT) and OAT3 (SLC22A8) among the main multi-specific "drug" transporters. They also transport numerous endogenous metabolites, raising the possibility of drug-metabolite interactions (DMI). To help understand the role of these drug transporters on metabolism across scales ranging from organ systems to organelles, a formal multi-scale analysis was performed. Metabolic network reconstructions of the omics-alterations resulting from Oat1 and Oat3 gene knockouts revealed links between the microbiome and human metabolism including reactions involving small organic molecules such as dihydroxyacetone, alanine, xanthine, and p-cresol-key metabolites in independent pathways. Interestingly, pairwise organ-or2022-01-01T00:00:00Z2022 Oct2026-05-03T10:53:53.421Z2025-04-19T02:35:05.875ZS-EPMC96228713631633910.1038/s41598-022-21091-w