Trial reportProceedings of the National Academy of Sciences of the United States of America2009
Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 322 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
322 citing papers in PubMed, 760 citations in OpenAlex.
- A simple method to measure sulfonation in man using paracetamol as probe drug.Scientific reports · 2021Trial
- Trial
- Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome.Parasites & vectors · 2018Trial
- Exploration of Biomarkers for Amoxicillin/Clavulanate-Induced Liver Injury: Multi-Omics Approaches.Clinical and translational science · 2017Trial
- Urinary 6β-Hydroxycortisol/Cortisol Ratio Most Highly Correlates With Midazolam Clearance Under Hepatic CYP3A Inhibition and Induction in Females: A Pharmacometabolomics Approach.The AAPS journal · 2016Trial
- Host diets drive microbiome evolution and functional divergence.Genes & diseases · 2027Review
- Pharmacomicrobiomics: From Host-Microbiome-Drug Interactions to Clinical Translation in Precision Medicine.Metabolites · 2026Review
- Application of metabolomics in drug-induced liver injury: A systematic review.Journal of translational internal medicine · 2026Article
- Methoxyacetic acid exposure in rats induces N-butyrylglycinuria consistent with beta-oxidation impairment.Archives of toxicology · 2026Article
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- Development of a gut microbiota model for the analysis of bacterial modifications of xenobiotics.Applied microbiology and biotechnology · 2026Article
- The relationship between gut microbiota and neurodegenerative diseases: a genetic and epigenetic perspective.Metabolic brain disease · 2026Review
- A sulfotransferase from a gut microbe acts on diverse phenolic sulfate compounds, including acetaminophen sulfate.PNAS nexus · 2026Article
- Clinical and biological significance of the relationship between gut microbiota and liver disease.World journal of hepatology · 2025Review
- Pharmacomicrobiomics: a new field contributing to optimizing drug therapy in Parkinson's disease.Gut microbes · 2025Review
- Clinical and metabolic phenotypes of Oxford Biobank subjects with variations in human flavin-containing monooxygenase 5 (FMO5).Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Vaginal pharmacomicrobiomics modulates risk of persistent and recurrent bacterial vaginosis.NPJ biofilms and microbiomes · 2025Review
- Gut Microbiota in Heart Failure-The Role of Inflammation.Biomedicines · 2025Review
- Gram-positive probiotics improves acetaminophen-induced hepatotoxicity by inhibiting leucine and Hippo-YAP pathway.Cell & bioscience · 2025Article
- Intestinal Microbiota Dysbiosis Role and Bacterial Translocation as a Factor for Septic Risk.International journal of molecular sciences · 2025Review
262 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary metabolite profiles were determined by (1)H NMR spectroscopy. The predose spectra were statistically analyzed in relation to drug metabolite excretion to detect predose biomarkers of drug fate and a human-gut microbiome cometabolite predictor was identified. Thus, we found that individuals having high predose urinary levels of p-cresol sulfate had low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide. We conclude that, in individuals with high bacterially mediated p-cresol generation, competitive O-sulfonation of p-cresol reduces the effective systemic capacity to sulfonate acetaminophen. Given that acetaminophen is such a widely used and seemingly well-understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach. However, we expect many other sulfonation reactions to be similarly affected by competition with p-cresol and our finding also has important implications for certain diseases as well as for the variable responses induced by many different drugs and xenobiotics. We propose that assessing the effects of microbiome activity should be an integral part of pharmaceutical development and of personalized health care. Furthermore, we envisage that gut bacterial populations might be deliberately manipulated to improve drug efficacy and to reduce adverse drug reactions.
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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 OpenQuestion graph.