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PharmacoMicrobiomics or how bugs modulate drugs: an educational initiative to explore the effects of human microbiome on drugs

by Ramy K Aziz, Rama Saad, Mariam R Rizkallah
BMC Bioinformatics (2011)

Cite this document (BETA)

Available from Ramy Aziz's profile on Mendeley.
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PharmacoMicrobiomics or how bugs modulate drugs: an educational initiative to explore the effects of human microbiome on drugs

MEETING ABSTRACT Open Access
PharmacoMicrobiomics or how bugs modulate
drugs: an educational initiative to explore the
effects of human microbiome on drugs
Ramy K Aziz1,2*, Rama Saad3, Mariam R Rizkallah4
From 10th Annual UT-ORNL-KBRIN Bioinformatics Summit 2011
Memphis, TN, USA. 1-3 April 2011
Background
Pharmacogenomics investigates how variations within the
human genome affect the action and disposition of drugs
as well as drug tolerance [1]. 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 dis-
ease [2,3]. However, the effect of these microbes on drugs
remains largely unexplored. Since microbes have complex
metabolism, including an extraordinary ability to metabo-
lize 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 [7].
Materials and methods
The PharmacoMicrobiomics initiative (http://pharma-
comicrobiomics.org) is a research-based educational
* Correspondence: ramy.aziz@egybio.net
1Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo
University, 11562 Cairo, Egypt
Full list of author information is available at the end of the article
Table 1 Examples of effects of gut microbes on drugs
CID Drug Body
Site
Microbial effects NCBI
PMID
64982 Baicalin [Potential antioxidant, anti-
inflammatory and liver tonic]
Gut Gut microbes hydrolyze baicalin and enhance its absorption. Absence of gut
microbiota resulted in lower levels of baicalin in plasma following oral
administration [8].
11197087
2724385 Digoxin [Cardiac glycoside] Gut Eubacterium lentum is responsible for the difference in metabolite concentration
of digoxin between North Americans and Southern Indians [9]
2759492
1794427 Chlorogenic acid [Antioxidant] Gut Variation in gut microbiome alters chlorogenic acid metabolism [10]. 12771329
1983 Acetaminophen [Analgesic and
antipyretic]
Gut Acetaminophen toxicity is associated with elevated levels of p-cresol produced by
some bacterial communities [4].
19667173
9064 (+)- catechin and (-)-epichatechins
[Anti-oxidants]
Gut 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 [11].
12659723
5734 Zonisamide [Anticonvulsant] Gut Gut microbiota reduce zonisamide into 2-sulfomoyacetylphenol. Levels of 2-
sulfomoyacetylphenol reportedly increased upon re-inoculation of germ-free rats
with gut microbiota [12]
9231340
Aziz et al. BMC Bioinformatics 2011, 12(Suppl 7):A10
http://www.biomedcentral.com/1471-2105/12/S7/A10
© 2011 Aziz et al; licensee 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.
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web platform that aims at exploring how microbes
modulate drugs. The project was launched as an edu-
cational platform to introduce bioinformatics and
microbial genomics to pharmacy students while bene-
fiting 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 pharmacody-
namic properties. Finally, participating students screen
and attempt to isolate fecal microbes that alter a speci-
fic drug, and each student selects a drug class and a
microbial species within a body site to examine their
complex interaction in vitro.
Conclusion
The literature-mining steps of the pharmacomicrobio-
mics project have resulted in the initiation of a continu-
ously 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 inter-
ested 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.
Author details
1Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo
University, 11562 Cairo, Egypt. 2Department of Computer Science, San Diego
State University, San Diego, CA, 92182, USA. 3Department of Biology, School
of Sciences and Engineering, The American University in Cairo, 11835 Cairo,
Egypt. 4Open Source Technologies Department, Information Technology
Institute, 12577 Giza, Egypt.
Published: 5 August 2011
References
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pharmacogenetics and pharmacogenomics: past lessons, future
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2. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI:
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8. Akao T, Kawabata K, Yanagisawa E, Ishihara K, Mizuhara Y, Wakui Y,
Sakashita Y, Kobashi K: Baicalin, the predominant flavone glucuronide of
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aglycone and restored to its original form. J Pharm Pharmacol 2000,
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9. Mathan VI, Wiederman J, Dobkin JF, Lindenbaum J: Geographic differences
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10. Gonthier MP, Verny MA, Besson C, Remesy C, Scalbert A: Chlorogenic acid
bioavailability largely depends on its metabolism by the gut microflora
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11. 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.
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doi:10.1186/1471-2105-12-S7-A10
Cite this article as: Aziz et al.: PharmacoMicrobiomics or how bugs
modulate drugs: an educational initiative to explore the effects of
human microbiome on drugs. BMC Bioinformatics 2011 12(Suppl 7):A10.
Figure 1 Pharmacogenetics investigates the effect of variations
within single genes on drugs; pharmacogenomics investigates the
effect of the sum of variations within the human genome on drugs;
pharmacomicrobiomics investigates the effect of variations within
the human microbiome on drugs.
Aziz et al. BMC Bioinformatics 2011, 12(Suppl 7):A10
http://www.biomedcentral.com/1471-2105/12/S7/A10
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