Microbiome-wide association studies link dynamic microbial consortia to disease

Journal name:
Nature
Volume:
535,
Pages:
94–103
Date published:
DOI:
doi:10.1038/nature18850
Received
Accepted
Published online

Abstract

Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramount for developing precision diagnostics and therapies that are based on the microbiome.

At a glance

Figures

  1. Sources of metabolites from the human microbiome.
    Figure 1: Sources of metabolites from the human microbiome.

    The core physiology of the microbial cells that make up the microbiome can produce by-products and intermediates that affect health, including short-chain fatty acids (such as acetate) and tryptophan metabolites. Secondary (or specialized) metabolites are produced from accessory genetic elements that are often transferred horizontally between microbes. Some of these metabolites, including colibactin15 and rhamnolipids109 (Rha-Rha-C10-C10), are known to cause disease. Microbes can also alter metabolites that are produced by the host, such as bile acids110 (CA, cholic acid) and even drugs that are consumed, such as acetaminophen (paracetamol)61. DCA, deoxycholic acid; Rha, rhamnose.

  2. Developing a microbial Global Positioning System to stratify individuals and to guide their treatment.
    Figure 2: Developing a microbial Global Positioning System to stratify individuals and to guide their treatment.

    An unstratified pool of individuals (black), all of whom have the same disease but with different underlying states (red, blue and grey), are stratified according to a biomarker from the microbiota, the microbiome or the metabolome (differentiated on a PCoA plot (bottom) or other analysis). This enables treatments to be chosen for each subpool, which facilitates movement from an 'unhealthy' region to a 'healthy' region of the microbial 'map'. The position of an individual in the main pool indicates the same person over time. The microbial Global Positioning System therefore enables determination of the current location of an individual in terms of their microbiome configuration, as well as a prediction of their final destination and directions for how to get there. Ideally, this moves all individuals in the pool to a healthy status (green) and microbiome, although in real-world situations no treatment will work perfectly. PC, principal coordinate.

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Affiliations

  1. Department of Surgery, University of Chicago, Chicago, Illinois 60637, USA.

    • Jack A. Gilbert
  2. Department of Pharmacology, University of California San Diego, La Jolla, California 92093, USA.

    • Robert A. Quinn,
    • Neha Garg &
    • Pieter C. Dorrestein
  3. Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, USA.

    • Robert A. Quinn,
    • Neha Garg &
    • Pieter C. Dorrestein
  4. Center for Microbiome Innovation, Jacobs School of Engineering, University of California, San Diego, La Jolla, California 92093, USA.

    • Robert A. Quinn,
    • Pieter C. Dorrestein &
    • Rob Knight
  5. Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California 92093, USA.

    • Justine Debelius,
    • Zhenjiang Z. Xu,
    • Pieter C. Dorrestein &
    • Rob Knight
  6. Department of Computer Science and Engineering, Jacobs School of Engineering, University of California San Diego, La Jolla, California 92093, USA.

    • James Morton &
    • Rob Knight
  7. Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99354, USA.

    • Janet K. Jansson

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