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Gut microbiota: a potential new territory for drug targeting

Abstract

The significant involvement of the gut microbiota in human health and disease suggests that manipulation of commensal microbial composition through combinations of antibiotics, probiotics and prebiotics could be a novel therapeutic approach. A systems perspective is needed to help understand the complex host–bacteria interactions and their association with pathophysiological phenotypes so that alterations in the composition of the gut microbiota in disease states can be reversed. In this article, we describe the therapeutic rationale and potential for targeting the gut microbiota, and discuss strategies and systems-oriented technologies for achieving this goal.

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Figure 1: Schematic view of how the gut microbiota affects host fat storage.
Figure 2: Schematic view of gut microbiota-targeted therapeutic strategy.
Figure 3: Metabolic profiling and urinary mammal–microbial metabolites in rats.

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Acknowledgements

This work was financially supported by the National Basic Research Program of China (2007CB914700) and the International Collaborative Project, Chinese Ministry of Science and Technology (2006DFA02700).

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Correspondence to Wei Jia.

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DATABASES

Entrez Genome Project

Bacteroides thetaiotaomicron

Clostridium difficile

Escherichia coli

Helicobacter pylori

Lactobacillus acidophilus

Lactobacillus casei

Methanobrevibacter smithii

OMIM

ADHD

inflammatory bowel disease

obesity

Tourette syndrome

FURTHER INFORMATION

The Consortium on Metabonomic Toxicology

Glossary

Metabonomics

The quantitative measurement of the multivariate metabolic responses of multicellular systems to pathophysiological stimuli or genetic modification. It is an approach to understanding the global metabolic regulation of an organism and its commensal and symbiotic partners.

Metagenomics

A culture-independent and sequence-based analysis of the collective microbial genomes contained in an environmental sample including soil, the oral cavity, faeces and aquatic habitats. The term is derived from the statistical concept of meta-analysis (the process of statistically combining separate analyses) and genomics (the comprehensive analysis of an organism's genetic material).

Microbiome

The entire set of microbial species living in the human body.

Pachinko model

A model for the illustration of xenobiotic metabolism in the host, in which the outcome of a xenobiotic is the result of a series of probabilistic interactions with endogenous and sym-endogenous elements.

Pharmaco-metabonomics

The prediction of the outcome of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures.

Prebiotics

A non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria that can improve host health.

Probiotics

Live microorganisms that, when administered in adequate amounts, confer a health benefit to the host.

Type III secretion system

A complex protein secretion and delivery system used by many animal- and plant-interacting bacteria, especially Gram-negative pathogenic bacteria, for delivering effector proteins into eukaryotic cells.

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Jia, W., Li, H., Zhao, L. et al. Gut microbiota: a potential new territory for drug targeting. Nat Rev Drug Discov 7, 123–129 (2008). https://doi.org/10.1038/nrd2505

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