Digestion of Plant Dietary miRNAs Starts in the Mouth under the Protection of Coingested Food Components and Plant-Derived Exosome-like Nanoparticles

Abstract

The regulatory functions of plant miRNAs on mammalian bodies are controversial, mainly because stability of the miRNAs in the digestive tract, as the prerequisite for their cross-kingdom effects, has somehow been overlooked. Hence, as the first stage of food ingestion, stability of plant miRNAs in human saliva has been investigated. The results show that plant miRNAs are of considerable resistance against salivary digestion, as surviving miRNAs more than 20 fM are detected. The stability varies dramatically, which can be explained by the difference in tertiary structure, governing their affinities to RNase. Surprisingly, miRNAs of low initial concentrations can end up with high survival rates after digestion. Plant miRNAs can be loaded into exosome-like nanoparticles (ELNs) and microcapsules formed by food components, both of which protect the miRNAs from being degraded in human saliva. Overall, plant miRNAs can apply certain strategies to maintain constant concentrations, paving the way for their potential cross-kingdom effects.

Quantitative analysis of miRNAs using SplintR ligase-mediated ligation of complementary-pairing probes enhanced by RNase H (SPLICER)-qPCR

“…However, a certain amount of miR159 (1.5 fM) survived after being in rat blood for 4 h. This agreed with the previous reports that miR159 was able to withstand RNase digestion under unfavorable oral and gastrointestinal conditions. 47 , 48 The quantification of miR159 by miRCURY was undesirable in terms of sensitivity and dynamic range. The method failed to detect the presence of miR159 after the injection for 2 h ( Figure 6 A), and the valid dynamic range (R 2 = 0.9871) only covered five orders of magnitude.…”

Plant miRNA bol-miR159 Regulates Gut Microbiota Composition in Mice: In Vivo Evidence of the Crosstalk between Plant miRNAs and Intestinal Microbes

“…6,8,10 Although the regulatory effects are still in debate, our recent findings showed that miR159 was of superior stability under the digestive conditions. 15,16 Chapado et al reported that the broccoli-derived miRNAs could survive common foodprocessing practices such as boiling, frying, microwaving, and steaming. Complete elimination of the miRNAs was not observed after the in vitro digestion stimulating oral, gastric and intestinal conditions.…”

“…Our recent works show that some plant miRNAs are able to resist the digestion and are absorbed by Caco-2 cells (a model cellline for intestinal epithelial cells). 15,16 Among them, bol-miR159 was observed with the highest stability and absorption efficiency, suggesting its presence in intestines of recipients and appreciable bioavailability. In 2016, Liu et al conducted a pioneering study exploring the cross-talk between gut microbiota and host miRNAs.…”

Dietary microRNAs: Could They Be Considered Nutraceuticals?

“…In this regard, recent animal model research discovered that plant microRNAs in their free form could be absorbed in the stomach through an SIDT1-dependent mechanism . Moreover, it has been demonstrated that the digestion of ingested microRNAs starts in the mouth by RNases present in the saliva and that the food matrix plays a key role in protecting their degradation by encapsulating the microRNAs with food components during mastication . Most microRNAs in fruits and vegetables are contained in exosome-like nanoparticles, which also protect microRNAs from degradation by RNases in the mouth.…”