The complex exogenous RNA spectra in human plasma: an interface with human gut biota?

PLoS One. 2012;7(12):e51009. doi: 10.1371/journal.pone.0051009. Epub 2012 Dec 10.


Human plasma has long been a rich source for biomarker discovery. It has recently become clear that plasma RNA molecules, such as microRNA, in addition to proteins are common and can serve as biomarkers. Surveying human plasma for microRNA biomarkers using next generation sequencing technology, we observed that a significant fraction of the circulating RNA appear to originate from exogenous species. With careful analysis of sequence error statistics and other controls, we demonstrated that there is a wide range of RNA from many different organisms, including bacteria and fungi as well as from other species. These RNAs may be associated with protein, lipid or other molecules protecting them from RNase activity in plasma. Some of these RNAs are detected in intracellular complexes and may be able to influence cellular activities under in vitro conditions. These findings raise the possibility that plasma RNAs of exogenous origin may serve as signaling molecules mediating for example the human-microbiome interaction and may affect and/or indicate the state of human health.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biota*
  • Gastrointestinal Tract
  • Humans
  • Metagenome
  • Plasma / metabolism*
  • RNA / blood*
  • RNA, Circular


  • RNA, Circular
  • RNA

Grant support

This work was supported by the University of Luxemburg program, research contracts from the Department of Defense (W911SR-07-C-0101, W81XWH-09-1-0107 and HDTRA 1-08-C-0023), and ATTRACT program grant (ATTRACT/A09/03) awarded by the Luxembourg National Research Fund (to PW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.