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Table 2 Contradicting evidence of cross-kingdom communication by diet/plant-derived miRNAs

From: MicroRNAs from plants to animals, do they define a new messenger for communication?

Year Contents miRNAs involved Source origin miRNA levels Refuting points Detection methods Conclusion Reference
2013 Little or no plant miRNAs or miR168a were detected in blood or liver of mice fed with rice-containing diets. miR168a Rice Unmeasurable The observed changes in LDL levels might be due to the release of endogenous cholesterol stores in response to negligible dietary cholesterol intake in mice fed with only rice. HTS, RT-qPCR, ELISA Dietary exposure to miR168a did not affect plasma LDL levels. Plasma LDL changes reported by Zhang resulted from nutritional imbalances between test and control groups rather than an RNAi-mediated effect of consuming miR168a in rice. [154]
2013 Plant miRNAs were not detectable in the plasma from healthy human subjects after intake of a western diet containing fruits. miR156a miR159a miR169a Plant material Undetectable Low measurable uptake RT-qPCR Horizontal delivery of miRNAs via oral ingestion of a typical diet was neither a frequent nor a prevalent event across multiple recipient animal organisms. [158]
  Negligible expression of miR21 in plasma or organ tissue in miR21 knockout mice after oral diets replete with endogenous miR21. miR21 Animal lard diet replete with miR21 Undetectable in plasma; less than one copy per cell in the liver, lungs, kidneys and stomach.     
Negligible expression of miR156a, miR159a and miR169a in plasma or organs in mice after diets replete with these miRNAs. miR156a
Vegetarian diets replete with these miRNAs miR156a: far less than one copy of miRNA per cell in liver, lungs, kidneys and stomach; miR159a and miR169a: undetectable in either plasma and/or organs.
  Negligible expression of plant-derived miRNAs in recipient honey bee tissues. miR156a
plant-derived miRNA Only miR156a but not miR159a or miR169a, was detected in abdominal tissue derived from nurses and foragers, but again at exceptionally low levels.
2012 Predominant monocot miR168 sequence was present as a result of contamination from a non-plant source. miR168a Plant Not available Contamination HTS, NB The observed plant miRNAs in animal sRNA datasets could originate in the process of sequencing, and accumulation of plant miRNAs via dietary exposure was not universal in animals. [155]
2014 Cross-contamination during library preparation was a source of exogenous RNAs. miR168a
Plant Not available Contamination HTS Variable amounts of plant miRNAs were found in publicly available sRNA-seq data sets of human tissues. [156]
2014 Failed to observe a postprandial increase in the brassica-specific miR824 or miR167a in broccoli sprouts feeding study. miR167a
Broccoli sprouts Below detection limit Low measurable uptake RT-qPCR Skeptical of the bioavailability and biologic activity of plant-borne miRNAs [157]
2013 Nonhuman primates failed to uptake dietary plant miRNAs. miR156
Fruit Not available The concentrations were too low to be specific and reliable. RT-qPCR,
droplet digital PCR
The level of miRNAs was too low to be true and/or amplification was non-specific. [159]
2018 Corn miRNA was extensively degraded in the GI tract and that the uptake into circulation and tissues was minimal. miR156a
Corn No corn miRNAs could be detected in whole blood, fecal or liver of animals. Significant degradation of corn miRNAs occurred during digestion.   No evidence of increased levels of corn miRNAs in whole blood or tissues after supplementation of corn miRNAs in the diet was observed in a mouse model. [160]
  1. MVs microvesicles, HTS high-throughput sequencing, NB Northern blot, WB Western blot, ELISA enzyme-linked immunosorbent assay, LDL low-density lipoprotein, sRNA small RNA