Research is never performed in isolation. It is built upon the foundations laid by prior knowledge and evaluated in the context of present knowledge. However, if data are not collected with a view toward integration, or if rich reference points do not exist, research is effectively performed in a vacuum. These are some of the challenges that a common reference can help to address, and the American Gut is a widely collaborative, carefully structured project that aims to provide such a reference. The establishment of a comprehensive reference encourages widespread use of standard protocols, since normalization of technical variation is essential when comparing results to the reference and assessing the significance of a study against the background population. Application of context-aware study designs that adhere to community-accepted standards used by references like the American Gut should minimize the time until microbiome research findings become medically actionable.
