Looking for Plant microRNAs in Human Blood Samples: Bioinformatics Evidence and Perspectives

Literature has proposed the existence of a cross kingdom regulation (CRK) between human and plants. In this context, microRNAs present in edible plants would be acquired through diet by the consumer’s organism and transported via bloodstream to tissues, where they would modulate gene expression. However, the validity of this phenomenon is strongly debated; indeed, some scholars have discussed both the methodologies and the results obtained in previous works. To date, only one study has performed a bioinformatics analysis on small RNA-sequencing data for checking the presence of plant miRNAs (pmiRNAs) in human plasma. For that investigation, the lack of reliable controls, which led to the misidentification of human RNAs as pmiRNAs, has been deeply criticized. Thus, in the present contribution, we aim to demonstrate the existence of pmiRNAs in human blood, adopting a bioinformatics approach characterized by more stringent conditions and filtering. The information obtained from 380 experiments produced in 5 different next generation sequencing (NGS) projects was examined, revealing the presence of 350 circulating pmiRNAs across the analysed data set. Although one of the NGS projects shows results likely to be attributed to sample contamination, the others appear to provide reliable support for the acquisition of pmiRNAs through diet. To infer the potential biological activity of the identified pmiRNAs, we predicted their putative human mRNA targets, finding with great surprise that they appear to be mainly involved in neurogenesis and nervous system development. Unfortunately, no consensus was identified within the sequences of detected pmiRNAs, in order to justify their stability or capability to be preserved in human plasma. We believe that the issue regarding CKR still needs further clarifications, even if the present findings would offer a solid support that this hypothesis is not impossible. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11130-023-01063-9.