Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma

Abstract

BackgroundThe human microbiome plays a significant role in maintaining normal physiology. Changes in its composition have been associated with bowel disease, metabolic disorders and atherosclerosis. Sequences of microbial origin have been observed within small RNA sequencing data obtained from blood samples. The aim of this study was to characterise the microbiome from which these sequences are derived.ResultsAbundant non-human small RNA sequences were identified in plasma and plasma exosomal samples. Assembly of these short sequences into longer contigs was the pivotal novel step in ascertaining their origin by BLAST searches. Most reads mapped to rRNA sequences. The taxonomic profiles of the microbes detected were very consistent between individuals but distinct from microbiomes reported at other sites. The majority of bacterial reads were from the phylum Proteobacteria, whilst for 5 of 6 individuals over 90% of the more abundant fungal reads were from the phylum Ascomycota; of these over 90% were from the order Hypocreales. Many contigs were from plants, presumably of dietary origin. In addition, extremely abundant small RNAs derived from human Y RNAs were detected.ConclusionsA characteristic profile of a subset of the human microbiome can be obtained by sequencing small RNAs present in the blood. The source and functions of these molecules remain to be determined, but the specific profiles are likely to reflect health status. The potential to provide biomarkers of diet and for the diagnosis and prognosis of human disease is immense.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-933) contains supplementary material, which is available to authorized users.

Dietary delivery: a new avenue for microRNA therapeutics?

“…In general, subsequent studies have focused on detecting exogenous sRNAs in the blood of mammals after a variety of feeding regimes. The results have been inconclusive, with some groups reporting data consistent with the original report [3,4] and others challenging the finding [5,6]. We review three recent studies [7][8][9] that provide further support for dietary delivery of sRNAs in mammals, and point to the therapeutic potential of using plant-produced miRNAs to combat diseases.…”

Sources and Functions of Extracellular Small RNAs in Human Circulation

“…exRNA from a panoply of different organisms including other animals (18), plants (21, 117, 129, 172, 205, 232), microorganisms (21, 117, 172, 205) and nematodes (32) has been reported in mammalian circulation (Figure 1). The first published report of plant miRNAs in human blood came from Chen-Yu Zhang’s group in 2012 (231).…”

“…In blood for instance non-coding RNAs (ncRNAs), including small regulatory RNAs (sRNAs) (12, 21, 50, 52, 63, 102, 111, 125, 139, 188, 196), non-coding RNAs (86, 199) as well as long coding RNAs (155, 179, 195) (Table 1), have been identified. sRNA are typically in the size range of between 15–200 nucleotides and comprise multiple different RNA biotypes including microRNAs (miRNAs) and others (Table 1).…”

“…Intriguingly, a number of recent studies suggest the presence of exogenous ex-sRNAs derived from the diet and/or microbiome in human plasma and serum (21, 117, 205). These findings, albeit controversial (53, 180, 187, 216, 220), suggest the possibility of ex-sRNA-mediated trans-kingdom regulation of gene expression (223, 231).…”

Negligible uptake and transfer of diet-derived pollen microRNAs in adult honey bees

“…Nonetheless, controversy remains. [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] The possibility of cross-kingdom regulation of gene expression via ingested miRNAs could be of particular interest in the mutualistic relationships of plants and their pollinators. The relationship involves an exchange of nutrients for the reproduction-enabling service of pollination, but is complicated by the antagonistic relationship of the two players, which is characterized by a fundamental conflict of interest.…”