- Meeting abstract
- Open Access
PharmacoMicrobiomics or how bugs modulate drugs: an educational initiative to explore the effects of human microbiome on drugs
© Aziz et al; licensee BioMed Central Ltd. 2011
Published: 5 August 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
Examples of effects of gut microbes on drugs
Baicalin [Potential antioxidant, anti-inflammatory and liver tonic]
Gut microbes hydrolyze baicalin and enhance its absorption. Absence of gut microbiota resulted in lower levels of baicalin in plasma following oral administration .
Digoxin [Cardiac glycoside]
Eubacterium lentum is responsible for the difference in metabolite concentration of digoxin between North Americans and Southern Indians 
Chlorogenic acid [Antioxidant]
Variation in gut microbiome alters chlorogenic acid metabolism .
Acetaminophen [Analgesic and antipyretic]
Acetaminophen toxicity is associated with elevated levels of p-cresol produced by some bacterial communities .
(+)- catechin and (-)-epichatechins [Anti-oxidants]
In germ-free rats, (+)-catechins and (-)-epicatechins resulted in increase in the levels of liver CYP450 2C11, and (+) catechins caused elevation in the specific activity of liver UGT-Chloramphenicol .
Gut microbiota reduce zonisamide into 2-sulfomoyacetylphenol. Levels of 2-sulfomoyacetylphenol reportedly increased upon re-inoculation of germ-free rats with gut microbiota 
- 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. 10.1080/03602530801952864PubMed CentralView ArticlePubMedGoogle Scholar
- Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI: The human microbiome project. Nature 2007, 449: 804–810. 10.1038/nature06244PubMed CentralView ArticlePubMedGoogle Scholar
- 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.096651.109PubMed CentralView ArticlePubMedGoogle Scholar
- 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.0904489106PubMed CentralView ArticlePubMedGoogle Scholar
- Wilson ID, Nicholson JK: The role of gut microbiota in drug response. Curr Pharm Des 2009, 15: 1519–1523. 10.2174/138161209788168173View ArticlePubMedGoogle Scholar
- Wilson ID: Drugs, bugs, and personalized medicine: pharmacometabonomics enters the ring. Proc Natl Acad Sci USA 2009, 106: 14187–14188.PubMed CentralView ArticlePubMedGoogle Scholar
- 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.View ArticleGoogle Scholar
- 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. 10.1211/0022357001777621View ArticlePubMedGoogle Scholar
- 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.30.7.971PubMed CentralView ArticlePubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- 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)00010-3View ArticlePubMedGoogle Scholar
- 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.xView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.