Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism

• DOI: 10.1073/pnas.0904489106
• Publication Date: 2009-08-11T01:28:49Z
• Authors: T. Andrew Clayton; David Baker; John C. Lindon; Jeremy R. Everett; Jeremy K. Nicholson
• Keywords: Acetaminophen; Glucuronide; Xenobiotic

We provide a demonstration in humans of the principle pharmacometabonomics by showing clear connection between an individual's metabolic phenotype, form predose urinary metabolite profile, and fate standard dose widely used analgesic acetaminophen. Predose postdose profiles were determined (1)H NMR spectroscopy. The spectra statistically analyzed relation to drug excretion detect biomarkers human-gut microbiome cometabolite predictor was identified. Thus, we found that individuals having high levels p-cresol sulfate had low ratios acetaminophen glucuronide. conclude that, with bacterially mediated generation, competitive O-sulfonation reduces effective systemic capacity sulfonate Given is such seemingly well-understood drug, this finding provides immense potential power pharmacometabonomic approach. However, expect many other sulfonation reactions be similarly affected competition our also has important implications for certain diseases as well variable responses induced different drugs xenobiotics. propose assessing effects activity should integral part pharmaceutical development personalized health care. Furthermore, envisage gut bacterial populations might deliberately manipulated improve efficacy reduce adverse reactions.