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Gut microorganisms, mammalian metabolism and personalized health care

Nature Reviews Microbiology volume 3, pages 431–438 (2005)Cite this article

Abstract

The mammalian gut microbiota interact extensively with the host through metabolic exchange and co-metabolism of substrates. Such metabolome–metabolome interactions are poorly understood, but might be implicated in the aetiology of many human diseases. In this paper, we assess the importance of the gut microbiota in influencing the disposition, fate and toxicity of drugs in the host, and conclude that appropriate consideration of individual human gut microbial activities will be a necessary part of future personalized health-care paradigms.

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Figure 1: Visualizing the host and gut-microbial co-metabolome interaction.
Figure 2: Urinary metabolites and gut microbiota conventionalization in rats.
Figure 3: Analysing microbiomes with CLOUDS.
Figure 4: Herbal medicines change sym-xenobiotic metabolism.

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Acknowledgements

We thank the BBSRC, EPSRC, The Wellcome Trust and NIH for funding this work. We also thank P. Elliot, J. Lindon and J. Scott (Imperial College, London), J. Utzinger and B. Singer (Princeton University, USA), J. Everett (Pfizer Global Research, UK), M. Bingham (University of Reading,UK) and F. Nicholson for their comments and discussion on this work and related subjects, as well as A. Nicholls (GlaxoSmithKline, UK) and R. Mortishire-Smith (Merck, Sharpe and Dohme, UK) for their assistance and previous collaboration on axenic rat conventionalization studies, and the COMET Team (H. Keun, M. Bollard, T. Ebbels, O. Beckonert) for their work on the CLOUDS analysis.

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Authors and Affiliations

  1. Biomedical Sciences Division, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ, UK

    Jeremy K. Nicholson & Elaine Holmes

  2. Department of Drug Metabolism and Pharmacokinetics, AstraZeneca Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK

    Ian D. Wilson

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  1. Jeremy K. Nicholson
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Correspondence to Jeremy K. Nicholson.

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DATABASES

Entrez

Bacteroides thetaiotaomicron

Escherichia coli

Clostridium botulinum

Glossary

ANGIOGENESIS

The growth and/or proliferation of new blood vessels, commonly occurring in response to malignant tissue.

COMBINATORIAL METABOLISM

The highly complex process whereby multiple independent metabolic systems (for example, in both host and microorganism) sequentially metabolize a compound, which results in a large number of possible metabolic products with diverse structures.

COX2 INHIBITORS

A relatively new class of non-steroidal anti-inflammatory drugs that block cyclooxygenase 2 (COX2) activity but do not inhibit COX1 enzymes that have gastro-protective effects. Therefore, unlike aspirin and other non-steroidal anti-inflammatory drugs, these compounds do not induce stomach irritation, but their safety has recently been called into question.

METABOLIC CAGE

A housing device for individual animals with the capacity to collect urine and/or faeces samples. These cages are commonly used to monitor the biochemical effects of drugs, toxins or other treatments over time.

METABOLIC TRAJECTORY

The visualization of the dynamic change in the multivariate metabolite profile of a biofluid or tissue with time, as projected using chemometric methods.

METABOLOME

The quantitative complement of all the low molecular weight molecules present in a biological sample.

METABOTYPE

The metabolic phenotype of an organism as measured from its biological fluids.

MICROBIOME

The entourage of associated microflora in a host.

MICROMETABOLITES

Drug metabolites that are present at microscopic levels (but varying between species), so that they are not normally characterized. These metabolites are often derived from combinatorial metabolism.

SYM-XENOBIOTIC

A metabolite that is formed by both gut-microbial and host metabolism but cannot be synthesized by either in isolation, and which forms no part of the energy metabolism or biosynthetic machinery of either system.

TOXICOGENOMICS

The study of the variation of an animal's genome and gene expression and their relationship to toxic effects of drugs and xenobiotics.

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Nicholson, J., Holmes, E. & Wilson, I. Gut microorganisms, mammalian metabolism and personalized health care. Nat Rev Microbiol 3, 431–438 (2005). https://doi.org/10.1038/nrmicro1152

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