ArticleJCI insight2023
The kidney drug transporter OAT1 regulates gut microbiome-dependent host metabolism.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Cardiovascular-kidney-metabolic syndrome through the lens of gut‑derived uremic toxins.Gut microbes · 2026Review
- A Kidney-Microbiome Short- and Medium-Chain Fatty Acid Loop Mediated by OAT1: Implications for the Remote Sensing and Signaling Theory.International journal of molecular sciences · 2026Article
- Article
- Aryl hydrocarbon receptor in the kidney regulates metabolic cross-talk with the liver and gut microbiome.Scientific reports · 2026Article
- Metabolic reprogramming in chronic kidney disease-cardiovascular disease comorbidity: from molecular mechanisms to therapeutic strategies.Frontiers in pharmacology · 2026Review
- Developmentally dynamic chromatin state at loci regulating organ crosstalk by remote sensing and signaling.Epigenetics & chromatin · 2025Article
- The autism-linked gut microbial metabolite p-cresol inhibits host catecholamine biosynthesizing enzymes to elicit social deficits.Communications biology · 2025Article
- From Discovery to Translation: Endogenous Substrates of OAT1 and OAT3 as Clinical Biomarkers for Renal Secretory Function.Clinical pharmacology and therapeutics · 2025Article
- Transporter-Mediated Interactions Between Uremic Toxins and Drugs: A Hidden Driver of Toxicity in Chronic Kidney Disease.International journal of molecular sciences · 2025Review
- Renal organic anion transporter 1: clinical relevance and the underlying mechanisms in chronic kidney disease.BMC nephrology · 2025Review
- Overview of pharmacodynamical research of traditional Chinese medicine on hyperuricemic nephropathy: from the perspective of dual-regulatory effect on the intestines and kidneys.Frontiers in pharmacology · 2025Review
- Association between delayed methotrexate metabolism, coagulation function, and adverse reactions in patients with acute lymphoblastic leukemia receiving high-dose methotrexate treatment.American journal of translational research · 2025Article
- In Vivo Regulation of Small Molecule Natural Products, Antioxidants, and Nutrients by OAT1 and OAT3.Nutrients · 2024Article
- Analysis of Polyphenol Extract from Hazel Leaf and Ameliorative Efficacy and Mechanism against Hyperuricemia Zebrafish Model via Network Pharmacology and Molecular Docking.Molecules (Basel, Switzerland) · 2024Article
- VARIDT 3.0: the phenotypic and regulatory variability of drug transporter.Nucleic acids research · 2024Article
- Effect of probenecid on blood levels and renal elimination of furosemide and endogenous compounds in rats: Discovery of putative organic anion transporter biomarkers.Biochemical pharmacology · 2023Article
- Remote effects of kidney drug transporter OAT1 on gut microbiome composition and urate homeostasis.JCI insight · 2023Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Organic anion transporter 1 (OAT1/SLC22A6, NKT) is a multispecific drug transporter in the kidney with numerous substrates, including pharmaceuticals, endogenous metabolites, natural products, and uremic toxins. Here, we show that OAT1 regulates levels of gut microbiome-derived metabolites. We depleted the gut microbiome of Oat1-KO and WT mice and performed metabolomics to analyze the effects of genotype (KO versus WT) and microbiome depletion. OAT1 is an in vivo intermediary between the host and the microbes, with 40 of the 162 metabolites dependent on the gut microbiome also impacted by loss of Oat1. Chemoinformatic analysis revealed that the altered metabolites (e.g., indoxyl sulfate, p-cresol sulfate, deoxycholate) had more ring structures and sulfate groups. This indicates a pathway from gut microbes to liver phase II metabolism, to renal OAT1-mediated transport. The idea that multiple gut-derived metabolites directly interact with OAT1 was confirmed by in vitro transport and magnetic bead binding assays. We show that gut microbiome-derived metabolites dependent on OAT1 are impacted in a chronic kidney disease (CKD) model and human drug-metabolite interactions. Consistent with the Remote Sensing and Signaling Theory, our results support the view that drug transporters (e.g., OAT1, OAT3, OATP1B1, OATP1B3, MRP2, MRP4, ABCG2) play a central role in regulating gut microbe-dependent metabolism, as well as interorganismal communication between the host and microbiome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.