Meta-analyses of studies of the human microbiota

  1. Rob Knight2,5,6,8
  1. 1Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado, Aurora, Colorado 80045, USA;
  2. 2BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA;
  3. 3Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
  4. 4Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108, USA;
  5. 5Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA;
  6. 6Howard Hughes Medical Institute, Boulder, Colorado 80309, USA
    1. 7 These authors contributed equally to this work.

    Abstract

    Our body habitat-associated microbial communities are of intense research interest because of their influence on human health. Because many studies of the microbiota are based on the same bacterial 16S ribosomal RNA (rRNA) gene target, they can, in principle, be compared to determine the relative importance of different disease/physiologic/developmental states. However, differences in experimental protocols used may produce variation that outweighs biological differences. By comparing 16S rRNA gene sequences generated from diverse studies of the human microbiota using the QIIME database, we found that variation in composition of the microbiota across different body sites was consistently larger than technical variability across studies. However, samples from different studies of the Western adult fecal microbiota generally clustered by study, and the 16S rRNA target region, DNA extraction technique, and sequencing platform produced systematic biases in observed diversity that could obscure biologically meaningful compositional differences. In contrast, systematic compositional differences in the fecal microbiota that occurred with age and between Western and more agrarian cultures were great enough to outweigh technical variation. Furthermore, individuals with ileal Crohn's disease and in their third trimester of pregnancy often resembled infants from different studies more than controls from the same study, indicating parallel compositional attributes of these distinct developmental/physiological/disease states. Together, these results show that cross-study comparisons of human microbiota are valuable when the studied parameter has a large effect size, but studies of more subtle effects on the human microbiota require carefully selected control populations and standardized protocols.

    Footnotes

    • 8 Corresponding author

      E-mail rob.knight{at}colorado.edu

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.151803.112.

      Freely available online through the Genome Research Open Access option.

    • Received March 4, 2013.
    • Accepted June 27, 2013.

    This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.

    | Table of Contents
    OPEN ACCESS ARTICLE

    Preprint Server