Evidence for plant-derived xenomiRs based on a large-scale analysis of public small RNA sequencing data from human samples

Abstract

In recent years, an increasing number of studies have reported the presence of plant miRNAs in human samples, which resulted in a hypothesis asserting the existence of plant-derived exogenous microRNA (xenomiR). However, this hypothesis is not widely accepted in the scientific community due to possible sample contamination and the small sample size with lack of rigorous statistical analysis. This study provides a systematic statistical test that can validate (or invalidate) the plant-derived xenomiR hypothesis by analyzing 388 small RNA sequencing data from human samples in 11 types of body fluids/tissues. A total of 166 types of plant miRNAs were found in at least one human sample, of which 14 plant miRNAs represented more than 80% of the total plant miRNA abundance in human samples. Plant miRNA profiles were characterized to be tissue-specific in different human samples. Meanwhile, the plant miRNAs identified from microbiome have an insignificant abundance compared to those from humans, while plant miRNA profiles in human samples were significantly different from those in plants, suggesting that sample contamination is an unlikely reason for all the plant miRNAs detected in human samples. This study also provides a set of testable synthetic miRNAs with isotopes that can be detected in situ after being fed to animals.

Predict plant-derived xenomiRs from plant miRNA sequences using random forest and one-dimensional convolutional neural network models

“…For sequence comparison, we collected 166 xenomiR sequences (positive samples) and 942 non-xenomiR sequences (negative samples). All 166 xenomiRs (Additional file 2: Table S1) were collected from our previous study [26], which were obtained from 388 healthy human samples analyzed by a rigorous bioinformatics pipeline. These miRNAs covered almost all the reported plant-derived xenomiRs so far.…”

“…Of interest, the functions of these xenomiRs seem to be consistent with previous studies (see details below). We have shown in our previous paper [26] that the plant miRNAs detected in human bodies are tissue-specific and cannot be fully explained by contamination and provided evidence for the xenomiRs hypothesis. The selective absorption of plant miRNAs by animal bodies could provide an explanation for studies where xenomiRs were not detected in animal bodies.…”

Recent Advances In Nutritional Sciences: An Overview Of Glycans And MiRNAs

“…The absorption of exomiRs in plant food has been a topic of controversy in past years [197,198]. The dietary delivery of miRNAs in humans is at least feasible [199], and several researchers recently found plant exogenous miRs in human samples [16,200]. Indeed, orally delivered therapeutic RNA strands, called short interfering RNA (siRNA) has been demonstrated in vivo [201].…”

Human Genes AreIn SilicoPotential Targets For Rice miRNA

“…pl-miR can enter the human body through the gastrointestinal tract and spread with blood in combination with proteins or as part of exosomes (Buck et al, 2014; Escrevente et al, 2011; Montecalvo et al, 2012; van der Grein & Nolte-’t Hoen, 2014). Many studies have shown that miRNAs that enter the gastrointestinal tract with food (dietary miRNA) are then found in various tissues (Chiang et al, 2015; Jonathan et al, 2013; Liang et al, 2015; Stephen & Snow, 2017; Vaucheret & Chupeau, 2012; Zempleni et al, 2017; Zhang et al, 2019; Zhang et al, 2012; Zhao et al, 2018). For example, аfter consumption of a fresh maize diet most zma-miRNAs were detected in the heart, brain, mammary gland, lung, liver, kidney and serum exosomes of pig (Luo et al, 2017).…”