XenomiRs and miRNA homeostasis in health and disease Evidence that diet and dietary miRNAs directly and indirectly influence circulating miRNA profiles

Contributions of dietary miRNAs to circulating small RNA profiles would have profound implications for interpretation of miRNA biomarker studies: presumptive disease-specific markers might instead indicate responses to disease-associated quantitative or qualitative dietary alteration. This examination weighs the evidence for a 2-fold hypothesis: first, that ingested biological matter contributes directly to the miRNA complement of body compartments; and second, that these diet-derived exogenous miRNAs (or xenomiRs) affect total miRNA profiles as part of a circulating miRNA homeostasis that is altered in many diseases. Homeostasis of high-density lipoprotein (HDL), a known miRNA carrier-provides a model as a proposed component of broader miRNA homeostasis. Further research into the dietary xenomiR hypothesis is needed to ensure rigor in the search for truly disease-specific miRNA biomarkers.