Determination of the potential bioavailability of plant microRNAs using a simulated human digestion process

Philip, Anna; Ferro, Valerie A.; Tate, Rothwelle J.

doi:10.1002/mnfr.201500137

Cited by 87 publications

(81 citation statements)

References 28 publications

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“…Different plant-based miRNAs are present within the cellular matrix of the plant material and may be associated with other plant molecules such as proteins and polysaccharides20. These components along with post-translational modifications may provide a conduit for dietary plant-derived miRNAs uptake20.…”

Section: Discussionmentioning

confidence: 99%

Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911

Yang

Hotz

Broadnax

et al. 2016

Sci Rep

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Inconsistent detection of plant-based dietary small RNAs in circulation has thwarted the use of dietary RNA therapeutics. Here we demonstrate mice consuming diets rich in vegetables displayed enhanced serum levels of the plant specific small RNA MIR2911. Differential centrifugation, size-exclusion chromatography, and proteinase K treatment of plant extracts suggest this RNA resides within a proteinase K-sensitive complex. Plant derived MIR2911 was more bioavailable than the synthetic RNA. Furthermore, MIR2911 exhibited unusual digestive stability compared with other synthetic plant microRNAs. The characteristics of circulating MIR2911 were also unusual as it was not associated with exosomes and fractionated as a soluble complex that was insensitive to proteinase K treatment, consistent with MIR2911 being stabilized by modifications conferred by the host. These results indicate that intrinsic stability and plant-based modifications orchestrate consumer uptake of this anomalous plant based small RNA and invite revisiting plant-based microRNA therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911

Yang

Hotz

Broadnax

et al. 2016

Sci Rep

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“…The xenomiR hypothesis is indirectly supported by studies showing that miRNAs extracted from plants (Philip et al 2015) or from body fluids (Chen et al 2008) are stable when subjected to high temperature or enzymatic digestions. Some in vivo studies support the initial finding that xenomiRs are present in body fluids of humans and other animals, however at a very low expression level (Wang et al 2012(Wang et al , 2013.…”

Section: Introductionmentioning

confidence: 99%

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

Kang

Bang-Berthelsen

Holm

et al. 2017

RNA

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miRNAs are small 22-nucleotide RNAs that can post-transcriptionally regulate gene expression. It has been proposed that dietary plant miRNAs can enter the human bloodstream and regulate host transcripts; however, these findings have been widely disputed. We here conduct the first comprehensive meta-study in the field, surveying the presence and abundances of cross-species miRNAs (xenomiRs) in 824 sequencing data sets from various human tissues and body fluids. We find that xenomiRs are commonly present in tissues (17%) and body fluids (69%); however, the abundances are low, comprising 0.001% of host human miRNA counts. Further, we do not detect a significant enrichment of xenomiRs in sequencing data originating from tissues and body fluids that are exposed to dietary intake (such as liver). Likewise, there is no significant depletion of xenomiRs in tissues and body fluids that are relatively separated from the main bloodstream (such as brain and cerebro-spinal fluids). Interestingly, the majority (81%) of body fluid xenomiRs stem from rodents, which are a rare human dietary contribution but common laboratory animals. Body fluid samples from the same studies tend to group together when clustered by xenomiR compositions, suggesting technical batch effects. Last, we performed carefully designed and controlled animal feeding studies, in which we detected no transfer of plant miRNAs into rat blood, or bovine milk sequences into piglet blood. In summary, our comprehensive computational and experimental results indicate that xenomiRs originate from technical artifacts rather than dietary intake.

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“…A new inter-kingdom communication concept in the field of circulating miRNAs is emerging, that is represented by the regulation of human mRNAs by exogenous miRNAs (or xenomiRs) that are most likely absorbed when food is ingested [58]. Exogenous miRNAs from vegetal origin are very stable and bioavailable even after extensive cooking [59]. Therefore, as circulating miRNAs are generally contained in microvesicles, why not assume that plants and vegetables also may contribute with their 'vesicles' to inter-kingdom communication?…”

Section: Key Figurementioning

confidence: 99%

How Our Other Genome Controls Our Epi-Genome

Celluzzi

Masotti

2016

Trends in Microbiology

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Determination of the potential bioavailability of plant microRNAs using a simulated human digestion process

Cited by 87 publications

References 28 publications

Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911

Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911

Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

How Our Other Genome Controls Our Epi-Genome

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