Meta-analyses of studies of the human microbiota
- Catherine Lozupone1,
- Jesse Stombaugh2,
- Antonio Gonzalez2,
- Gail Ackermann2,
- Doug Wendel2,
- Yoshiki Vazquez-Baeza2,
- Janet K. Jansson3,
- Jeffrey I. Gordon4 and
- Rob Knight2,5
- 1 University of Colorado at Denver;
- 2 University of Colorado at Boulder;
- 3 Lawrence Berkeley National Laboratory;
- 4 Washington University School of Medicine
- ↵* Corresponding author; email: rob.knight{at}colorado.edu
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 (http://www.microbio.me/qiime/), 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 requires carefully selected control populations and standardized protocols.
- Received March 4, 2013.
- Accepted June 27, 2013.
- © 2013, Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
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/.
