- Meeting abstract
- Open Access
PharmacoMicrobiomics or how bugs modulate drugs: an educational initiative to explore the effects of human microbiome on drugs
BMC Bioinformaticsvolume 12, Article number: A10 (2011)
Pharmacogenomics investigates how variations within the human genome affect the action and disposition of drugs as well as drug tolerance . Yet, variations within the human genome do not fully account for the tremendous phenotypic variations observed between individuals. Human-associated microbes, which exceed the human cells in number, significantly contribute to the effective human gene pool, and their combined genomes (known as the human microbiome) have not gained attention until recently. The Human Microbiome Project was launched in 2007 to catalogue the tremendous diversity of cultured and uncultured human-associated microbial communities residing in different human tissues, and to study the effect of microbial genes and genomes on human health and disease [2, 3]. However, the effect of these microbes on drugs remains largely unexplored. Since microbes have complex metabolism, including an extraordinary ability to metabolize xenobiotics [4–6], they are expected to play a pivotal role in modulating the action, disposition, and toxicity of drugs with which they interact in different sub-ecosystems within the human body .
Materials and methods
The PharmacoMicrobiomics initiative (http://pharmacomicrobiomics.org) is a research-based educational web platform that aims at exploring how microbes modulate drugs. The project was launched as an educational platform to introduce bioinformatics and microbial genomics to pharmacy students while benefiting the research community. The first step of this project was mining existing literature and extracting known microbe-drug interactions using a combination of keywords in an iterative process. The second step was the manual curation of the extracted literature data and their classification by drug classes, microbial families, and body systems (e.g., Table 1). The third step is the creation of a relational database that includes the microbes at different body sites and their effects on drugs’ pharmacokinetic and pharmacodynamic properties. Finally, participating students screen and attempt to isolate fecal microbes that alter a specific drug, and each student selects a drug class and a microbial species within a body site to examine their complex interaction in vitro.
The literature-mining steps of the pharmacomicrobiomics project have resulted in the initiation of a continuously updated web portal maintained by students (http://pharmacomicrobiomics.org/papers and http://pharmacomicrobiomics.com/examples.html). The project is expected to build a knowledge base that allows interested students and scholars, in the future, to predict the behavior of untested members of drug classes or unstudied microbial species, and to design laboratory experiments for testing these predictions.
Nebert DW, Zhang G, Vesell ES: From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions. Drug Metab Rev 2008, 40: 187–224. 10.1080/03602530801952864
Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI: The human microbiome project. Nature 2007, 449: 804–810. 10.1038/nature06244
Peterson J, Garges S, Giovanni M, McInnes P, Wang L, Schloss JA, Bonazzi V, McEwen JE, Wetterstrand KA, Deal C, et al.: The NIH Human Microbiome Project. Genome Res 2009, 19: 2317–2323. 10.1101/gr.096651.109
Clayton TA, Baker D, Lindon JC, Everett JR, Nicholson JK: Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci USA 2009, 106: 14728–14733. 10.1073/pnas.0904489106
Wilson ID, Nicholson JK: The role of gut microbiota in drug response. Curr Pharm Des 2009, 15: 1519–1523. 10.2174/138161209788168173
Wilson ID: Drugs, bugs, and personalized medicine: pharmacometabonomics enters the ring. Proc Natl Acad Sci USA 2009, 106: 14187–14188.
Rizkallah M, Saad R, Aziz R: The Human Microbiome Project, personalized medicine and the birth of pharmacomicrobiomics. Cur Pharmacog Personalized Med (Formerly Current Pharmacog) 2010, 8: 182–193.
Akao T, Kawabata K, Yanagisawa E, Ishihara K, Mizuhara Y, Wakui Y, Sakashita Y, Kobashi K: Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. J Pharm Pharmacol 2000, 52: 1563–1568. 10.1211/0022357001777621
Mathan VI, Wiederman J, Dobkin JF, Lindenbaum J: Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora. Gut 1989, 30: 971–977. 10.1136/gut.30.7.971
Gonthier MP, Verny MA, Besson C, Remesy C, Scalbert A: Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J Nutr 2003, 133: 1853–1859.
Lhoste EF, Ouriet V, Bruel S, Flinois JP, Brezillon C, Magdalou J, Cheze C, Nugon-Baudon L: The human colonic microflora influences the alterations of xenobiotic-metabolizing enzymes by catechins in male F344 rats. Food Chem Toxicol 2003, 41: 695–702. 10.1016/S0278-6915(03)00010-3
Kitamura S, Sugihara K, Kuwasako M, Tatsumi K: The role of mammalian intestinal bacteria in the reductive metabolism of zonisamide. J Pharm Pharmacol 1997, 49: 253–256. 10.1111/j.2042-7158.1997.tb06790.x