Diet-derived microRNAs: unicorn or silver bullet?

Witwer, Kenneth W.; Zhang, Chen Yu

doi:10.1186/s12263-017-0564-4

Cited by 51 publications

(38 citation statements)

References 60 publications

(137 reference statements)

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“…First suggested for plant small RNA (Timmons & Fire, ; Whangbo & Hunter, ; Witwer & Zhang, ; Zhou et al., ) and more specifically rice microRNAs in a highly controversial study (Zhang et al., ), dietary microRNAs bioavailability found more solid ground when milk was considered as their carriers for transfer between individuals or species, yet not without sparking an intense debate (Auerbach et al., ; Fabris & Calin, ; Kang et al., ; Melnik et al., , ; Melnik & Schmitz, ; Witwer, , ; Witwer & Halushka, ; Witwer & Hirschi, ; Witwer et al., ; Zempleni, ; Zempleni et al., ; Zempleni et al., ; Zhou et al., ).…”

Section: Milk Micrornas In Health and Diseasementioning

confidence: 99%

Milk MicroRNAs in Health and Disease

Benmoussa

Provost

2019

Comp Rev Food Sci Food Safe

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MicroRNAs are small noncoding RNAs responsible for regulating 40% to 60% of gene expression at the posttranscriptional level. The discovery of circulating microRNAs in several biological fluids opened the path for their study as biomarkers and long‐range cell‐to‐cell communication mediators. Their transfer between individuals in the case of blood transfusion, for example, and their high enrichment in milk have sparked the interest for microRNA transfer through diet, especially from mothers to infants during breastfeeding. The extension of such paradigm led to the study of milk microRNAs in the case of cow or goat milk consumption in adults. Here we provide a comprehensive critical review of the key findings surrounding milk microRNAs in human, cow, and goat milk among other species. We discuss the data on their biological properties, their use as disease biomarkers, their transfer between individuals or species, and their putative or verified functions in health and disease of infants and adult consumers. This work is based on all the literature available and integrates all the results, theories, debates, and validation studies available so far on milk microRNAs and related areas of investigations. We critically discuss the limitations and outline future aspects and avenues to explore in this rapidly growing field of research that could impact public health through infant milk formulations or new therapies. We hope that this comprehensive review of the literature will provide insight for all teams investigating milk RNAs’ biological activities and help ensure the quality of future reports.

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Section: Milk Micrornas In Health and Diseasementioning

confidence: 99%

Milk MicroRNAs in Health and Disease

Benmoussa

Provost

2019

Comp Rev Food Sci Food Safe

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“…Additionally, exogenous RNAs have been reported in the blood plasma of humans and mice [ 20 , 21 ], sparking a heated debate around the genuineness of these observations [ 22 – 25 ]. While bacteria do secrete RNAs via outer membrane vesicles [ 26 – 28 ], the potential for exogenous RNA-based signalling in mammals is also the subject of significant current debate [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Small RNA profiling of low biomass samples: identification and removal of contaminants

et al. 2018

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BackgroundSequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. DNA contamination has been previously reported, yet contamination with RNA is usually considered to be very unlikely due to its inherent instability. Small RNAs (sRNAs) identified in tissues and bodily fluids, such as blood plasma, have implications for physiology and pathology, and therefore the potential to act as disease biomarkers. Thus, the possibility for RNA contaminants demands careful evaluation.ResultsHerein, we report on the presence of small RNA (sRNA) contaminants in widely used microRNA extraction kits and propose an approach for their depletion. We sequenced sRNAs extracted from human plasma samples and detected important levels of non-human (exogenous) sequences whose source could be traced to the microRNA extraction columns through a careful qPCR-based analysis of several laboratory reagents. Furthermore, we also detected the presence of artefactual sequences related to these contaminants in a range of published datasets, thereby arguing in particular for a re-evaluation of reports suggesting the presence of exogenous RNAs of microbial and dietary origin in blood plasma. To avoid artefacts in future experiments, we also devise several protocols for the removal of contaminant RNAs, define minimal amounts of starting material for artefact-free analyses, and confirm the reduction of contaminant levels for identification of bona fide sequences using ‘ultra-clean’ extraction kits.ConclusionThis is the first report on the presence of RNA molecules as contaminants in RNA extraction kits. The described protocols should be applied in the future to avoid confounding sRNA studies.Electronic supplementary materialThe online version of this article (10.1186/s12915-018-0522-7) contains supplementary material, which is available to authorized users.

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“…Diet-derived exogenous microRNAs have been proposed to exert an influence on human physiology (Liang et al 2014;Baier et al 2014), as have bacterial RNAs, which can be secreted in the protective environment of outer membrane vesicles (Ghosal et al 2015;Celluzzi and Masotti 2016;Blenkiron et al 2016). However, a heated discussion has at the same time been triggered around the genuineness of the observations of these exogenous sRNAs in human blood (Witwer 2015;Kang et al 2017;Witwer and Zhang 2017) and the possibility of dietary uptake of sRNAs (Dickinson et al 2013;Witwer and Hirschi 2014;Title et al 2015). This discussion happens at a time where DNA sequencing-based analyses of low-biomass samples have been recognized to be prone to confounding by contaminants (Lusk 2014).…”

Section: Introductionmentioning

confidence: 99%

Isolation of nucleic acids from low biomass samples: detection and removal of sRNA contaminants

Heintz‐Buschart

Yusuf

Kaysen

et al. 2017

Preprint

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Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments.Due to its inherent instability, contamination with RNA is usually considered to be unlikely. Here we report the presence of small RNA (sRNA) contaminants in widely used microRNA extraction kits and means for their depletion. Sequencing of sRNAs extracted from human plasma samples was performed and significant levels of non-human (exogenous) sequences were detected. The source of the most abundant of these sequences could be traced to the microRNA extraction columns by qPCRbased analysis of laboratory reagents. The presence of artefactual sequences originating from the confirmed contaminants were furthermore replicated in a range of published datasets. To avoid artefacts in future experiments, several protocols for the removal of the contaminants were elaborated, minimal amounts of starting material for artefact-free analyses were defined, and the reduction of contaminant levels for identification of bona fide sequences using 'ultra-clean' extraction kits was confirmed. In conclusion, this is the first report of the presence of RNA molecules as contaminants in laboratory reagents. The described protocols should be applied in the future to avoid confounding sRNA studies.

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Diet-derived microRNAs: unicorn or silver bullet?

Cited by 51 publications

References 60 publications

Milk MicroRNAs in Health and Disease

Milk MicroRNAs in Health and Disease

Small RNA profiling of low biomass samples: identification and removal of contaminants

Isolation of nucleic acids from low biomass samples: detection and removal of sRNA contaminants

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