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A Metagenomic Meta-Analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome

Courtney Armour, Stephen Nayfach, Katherine Pollard, Thomas Sharpton
doi: https://doi.org/10.1101/286419
Courtney Armour
1Molecular and Cellular Biology Program, Oregon State University, Corvallis, OR, USA
2Department of Microbiology, Oregon State University, Corvallis, OR, USA
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Stephen Nayfach
3Department of Energy Joint Genome Institute, Walnut Creek, California, USA
4Gladstone Institutes, San Francisco, CA, USA
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Katherine Pollard
4Gladstone Institutes, San Francisco, CA, USA
5Department of Epidemiology & Biostatistics, Institute for Human Genetics, Quantitative Biology Institute, and Institute for Computational Health Sciences, University of California, San Francisco, CA, USA
6Chan-Zuckerberg Biohub, San Francisco, CA, USA
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Thomas Sharpton
2Department of Microbiology, Oregon State University, Corvallis, OR, USA
7Department of Statistics, Oregon State University, Corvallis, OR, USA
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  • For correspondence: thomas.sharpton@oregonstate.edu
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ABSTRACT

While recent research indicates that human health depends, in part, upon the symbiotic relationship between gut microbes and their host, the specific interactions between host and microbe that define health are poorly resolved. Metagenomic clinical studies clarify this definition by revealing gut microbial taxa and functions that stratify healthy and diseased individuals. However, the typical single-disease focus of microbiome studies limits insight into which microbiome features robustly associate with health, indicate general deviations from health, or predict specific diseases. Additionally, the focus on taxonomy may limit our understanding of how the microbiome relates to health given observations that different taxonomic members can fulfill similar functional roles. To improve our understanding of the association between the gut microbiome and health, we integrated about 2,000 gut metagenomes obtained from eight clinical studies in a statistical meta-analysis. We identify characteristics of the gut microbiome that associate generally with disease, including functional alpha-diversity, beta-diversity, and beta-dispersion. Moreover, we resolve microbiome modules that stratify diseased individuals from controls in a manner independent of study-specific effects. Many of the differentially abundant functions overlap multiple diseases suggesting a role in host health, while others are specific to a single disease and may associate with disease-specific etiologies. Our results clarify potential microbiome-mediated mechanisms of disease and reveal features of the microbiome that may be useful for the development of microbiome-based diagnostics. Ultimately, our study clarifies the definition of a healthy microbiome and how perturbations to it associate with disease.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 23, 2018.
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A Metagenomic Meta-Analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome
Courtney Armour, Stephen Nayfach, Katherine Pollard, Thomas Sharpton
bioRxiv 286419; doi: https://doi.org/10.1101/286419
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A Metagenomic Meta-Analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome
Courtney Armour, Stephen Nayfach, Katherine Pollard, Thomas Sharpton
bioRxiv 286419; doi: https://doi.org/10.1101/286419

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