Abstract
A broader understanding towards factors underlying inter-individual variation in pharmacotherapy is important for our pursuit of "personalized medicine". Based on knowledge gleaned from the investigation of the human genetics, drug metabolizing enzymes and transporters, clinicians and pharmacists are able to tailor pharmacotherapies according to the genotype of patients. However, human host factors only form part of the equation that accounts for heterogeneity in therapeutic outcome. Notably, the gut microbiota possesses wide ranging metabolic activities that expands the metabolic functions of the human host beyond that encoded by the human genome. This review will first illustrate with examples the mechanisms in which gut microbes modulate pharmacokinetics and therapeutic outcome. Secondly, we discuss the application of metabonomics in deciphering the complex host-gut microbiota interaction in pharmacotherapy. Thirdly, we highlight an integrative approach with particular mention of the investigation of gut microbiota using culture-based and culture-independent techniques to complement the investigation of the host-gut microbiota axes in pharmaceutical research.
- clinical pharmacology
- cytochrome P450
- drug efficacy
- drug toxicity
- drug-drug interactions
- gas chromatography/GC/MS
- glucuronidation/UDP-glucuronyltransferases/UGT
- microbiome
- pharmacokinetics
- systems biology
- The American Society for Pharmacology and Experimental Therapeutics