Abstract
The recent description of the presence of exogenous plant microRNAs from rice in human plasma had profound implications for the interpretation of microRNAs function in human health. If validated, these results suggest that food should not be considered only as a macronutrient and micronutrient supplier but it could also be a way of genomic interchange between kingdoms. Subsequently, several studies have tried to replicate these results in rice and other plant foods and most of them have failed to find plant microRNAs in human plasma. In this scenario, we aimed to detect plant microRNAs in beer and extra virgin olive oil (EVOO) - two plant-derived liquid products frequently consumed in Spain - as well as in human plasma after an acute ingestion of EVOO. Our hypothesis was that microRNAs present in beer and EVOO raw material could survive manufacturing processes, be part of these liquid products, be absorbed by human gut and circulate in human plasma. To test this hypothesis, we first optimized the microRNA extraction protocol to extract microRNAs from beer and EVOO, and then tried to detect microRNAs in those samples and in plasma samples of healthy volunteers after an acute ingestion of EVOO.
Similar content being viewed by others
Abbreviations
- EVOO:
-
Extra virgin olive oil
- NGS:
-
Next generation sequencing
- NTC:
-
Non-template control
- TMD:
-
Traditional mediterranean diet
- RT-qPCR:
-
Real-time quantitative PCR
References
Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY (2012) Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res 22(1):107–126. doi:10.1038/cr.2011.158
Jiang M, Sang X, Hong Z (2012) Beyond nutrients: food-derived microRNAs provide cross-kingdom regulation. BioEssays 34(4):280–284. doi:10.1002/bies.201100181
Witwer KW, Hirschi KD (2014) Transfer and functional consequences of dietary microRNAs in vertebrates: concepts in search of corroboration: negative results challenge the hypothesis that dietary xenomiRs cross the gut and regulate genes in ingesting vertebrates, but important questions persist. BioEssays 36(4):394–406. doi:10.1002/bies.201300150
Sherman JH, Munyikwa T, Chan SY, Petrick JS, Witwer KW, Choudhuri S (2015) RNAi technologies in agricultural biotechnology: The Toxicology Forum 40th Annual Summer Meeting. Regul Toxico Pharm 73(2):671–680. doi:10.1016/j.yrtph.2015.09.001
Dickinson B, Zhang Y, Petrick JS, Heck G, Ivashuta S, Marshall WS (2013) Lack of detectable oral bioavailability of plant microRNAs after feeding in mice. Nat Biotechnol 31(11):965–967. doi:10.1038/nbt.2737
Witwer KW, McAlexander MA, Queen SE, Adams RJ (2013) Real-time quantitative PCR and droplet digital PCR for plant miRNAs in mammalian blood provide little evidence for general uptake of dietary miRNAs: limited evidence for general uptake of dietary plant xenomiRs. RNA Biol 10(7):1080–1086. doi:10.4161/rna.25246
Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Gomez-Gracia E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Martinez-Gonzalez MA, Investigators PS (2013) Primary prevention of cardiovascular disease with a Mediterranean diet. New Engl J Med 368(14):1279–1290. doi:10.1056/NEJMoa1200303
Estruch R, Urpí N, Chiva G, Romero ES, Covas MI, Salas-Salvadó J, Wärnberg L, Lamuela-Raventós RM (2010) Cerveza, dieta Mediterránea y enfermedad cardiovascular. Centro de Información Cerveza y Salud (CICS):1–83
Covas MI, Konstantinidou V, Fito M (2009) Olive oil and cardiovascular health. J Cardiovasc Pharm 54(6):477–482. doi:10.1097/FJC.0b013e3181c5e7fd
Bayram B, Esatbeyoglu T, Schulze N, Ozcelik B, Frank J, Rimbach G (2012) Comprehensive analysis of polyphenols in 55 extra virgin olive oils by HPLC-ECD and their correlation with antioxidant activities. Plant Foods Hum Nutr 67(4):326–336. doi:10.1007/s11130-012-0315-z
Pérez-Jiménez J, Elena Díaz-Rubio M, Saura-Calixto F (2015) Contribution of macromolecular antioxidants to dietary antioxidant capacity: a study in the Spanish Mediterranean diet. Plant Foods Hum Nutr 70(4):365–370. doi:10.1007/s11130-015-0513-6
Donaire L, Pedrola L, Rosa Rde L, Llave C (2011) High-throughput sequencing of RNA silencing-associated small RNAs in olive (Olea europaea L.). PLoS One 6(11):e27916. doi:10.1371/joursnal.pone.0027916
Chen X, Gao C, Li H, Huang L, Sun Q, Dong Y, Tian C, Gao S, Dong H, Guan D, Hu X, Zhao S, Li L, Zhu L, Yan Q, Zhang J, Zen K, Zhang CY (2010) Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products. Cell Res 20(10):1128–1137. doi:10.1038/cr.2010.80
Hata T, Murakami K, Nakatani H, Yamamoto Y, Matsuda T, Aoki N (2010) Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs. Biochem Biophys Res Commun 396(2):528–533. doi:10.1016/j.bbrc.2010.04.135
Title AC, Denzler R, Stoffel M (2015) Uptake and function studies of maternal milk-derived MicroRNAs. J Biol Chem 290(39):23680–23691. doi:10.1074/jbc.M115.676734
Alsaweed M, Hartmann PE, Geddes DT, Kakulas F (2015) MicroRNAs in breastmilk and the lactating breast: potential immunoprotectors and developmental regulators for the infant and the mother. Int J Environ Res Public Health 12(11):13981–14020. doi:10.3390/ijerph121113981
Snow JW, Hale AE, Isaacs SK, Baggish AL, Chan SY (2013) Ineffective delivery of diet-derived microRNAs to recipient animal organisms. RNA Biol 10(7):1107–1116. doi:10.4161/rna.24909
Baier SR, Nguyen C, Xie F, Wood JR, Zempleni J (2014) MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers. J Nutr 144(10):1495–1500. doi:10.3945/jn.114.196436
Mestdagh P, Hartmann N, Baeriswyl L, Andreasen D, Bernard N, Chen C, Cheo D, D'Andrade P, DeMayo M, Dennis L, Derveaux S, Feng Y, Fulmer-Smentek S, Gerstmayer B, Gouffon J, Grimley C, Lader E, Lee KY, Luo S, Mouritzen P, Narayanan A, Patel S, Peiffer S, Ruberg S, Schroth G, Schuster D, Shaffer JM, Shelton EJ, Silveria S, Ulmanella U, Veeramachaneni V, Staedtler F, Peters T, Guettouche T, Wong L, Vandesompele J (2014) Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study. Nat Methods 11(8):809–815. doi:10.1038/nmeth.3014
Tosar JP, Rovira C, Naya H, Cayota A (2014) Mining of public sequencing databases supports a non-dietary origin for putative foreign miRNAs: underestimated effects of contamination in NGS. RNA 20(6):754–757. doi:10.1261/rna.044263.114
Lusk RW (2014) Diverse and widespread contamination evident in the unmapped depths of high throughput sequencing data. PLoS one 9(10):e110808. doi:10.1371/journal.pone.0110808
Acknowledgments
The present work was funded by the Fundación Cerveza y Salud, Fundación Salud 2000 – Merck-Serono research fellowship and Instituto de Salud Carlos III (PI14/01374). VM was supported by a Manuel de Oya fellowship of the Fundación Cerveza y Salud. LD and JMO conceived the study idea and designed the research. VM carried out experimental approaches. LD and MAL conducted the intervention study. RM and LD carried out the sequencing analyses. LD and VM wrote the manuscript and all authors assisted in manuscript revision and approved it.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest Statement
The authors declare that they have no conflict of interests. However it worths mentioning that part of this work has been funded by Fundación Cerveza y Salud that is a non-profit scientific organization aimed to study the relationship between beer consumption and health.
Electronic supplementary material
ESM 1
(DOCX 23.1 kb)
Rights and permissions
About this article
Cite this article
Micó, V., Martín, R., Lasunción, M.A. et al. Unsuccessful Detection of Plant MicroRNAs in Beer, Extra Virgin Olive Oil and Human Plasma After an Acute Ingestion of Extra Virgin Olive Oil. Plant Foods Hum Nutr 71, 102–108 (2016). https://doi.org/10.1007/s11130-016-0534-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11130-016-0534-9