Table9_Investigation of the transability of dietary small non-coding RNAs to animals.DOCX

Our daily diet not only provides essential nutrients needed for survival and growth but also supplies bioactive ingredients to promote health and prevent disease. Recent studies have shown that exogenous microRNAs (miRNAs), xenomiRs, may enter the consumer’s body through dietary intake and regulate gene expression. This fascinating phenomenon suggests that xenomiRs can act as a new class of bioactive substances associated with mammalian systems. In contrast, several studies have failed to detect xenomiRs in consumers and reported that the observed diet-derived miRNAs in the previous studies can be related to the false positive effects of experiments. This discrepancy can be attributed to the potential artifacts related to the process of experiments, small sample size, and inefficient bioinformatics pipeline. Since this hypothesis is not generally accepted yet, more studies are required. Here, a stringent and reliable bioinformatics pipeline was used to analyze 133 miRNA sequencing data from seven different studies to investigate this phenomenon. Generally, our results do not support the transfer of diet-derived miRNAs into the animal/human tissues in every situation. Briefly, xenomiRs were absent from most samples, and also, their expressions were very low in the samples where they were present, which is unlikely to be sufficient to regulate cell transcripts. Furthermore, this study showed that the possibility of miRNAs being absorbed through animals’ diets and thus influencing gene expression during specific periods of biological development is not inconceivable. In this context, our results were in agreement with the theory of the transfer of small RNAs under certain conditions and periods as xenomiRs were found in colostrum which may modulate infants’ immune systems via post-transcriptional regulation. These findings provide evidence for the selective absorption of diet-derived small RNAs, which need to be investigated in future studies to shed light on the mechanisms underlying the transference of diet-derived miRNAs.

日常膳食不仅为机体生存与生长提供必需营养物质，还能提供可促进健康、预防疾病的生物活性成分。近期研究证实，外源性微小RNA（microRNAs, miRNAs）——即异种miRNA（xenomiRs）——可通过膳食摄入进入宿主体内，进而调控基因表达。这一现象提示，异种miRNA可作为一类新型生物活性物质，与哺乳动物机体系统密切相关。
与之相反，多项研究未能在受试个体体内检测到异种miRNA，并指出既往研究中观测到的膳食来源miRNA，可能与实验中的假阳性效应相关。上述研究结论的分歧，可归因于实验流程相关的潜在人为误差、样本量过小，以及生物信息学分析流程（bioinformatics pipeline）不够完善。由于该假说尚未得到广泛认可，仍需开展更多相关研究。
本研究采用严格可靠的生物信息学分析流程，对来自7项独立研究的133份miRNA测序数据进行分析，以探究这一现象。总体而言，本研究结果并不支持“膳食来源miRNA可在所有情况下转移至动物或人体组织”这一结论。简言之，绝大多数样本中未检测到异种miRNA；即便在少量检出的样本中，其表达水平也极低，不足以调控细胞转录本的表达。此外，本研究显示，在生物发育的特定阶段，动物通过膳食吸收miRNA并进而影响基因表达的可能性并非不存在。在此背景下，本研究结果与“小RNA可在特定条件和时期发生转移”的理论相符——研究在初乳（colostrum）中检测到了异种miRNA，其可能通过转录后调控（post-transcriptional regulation）机制调节婴儿的免疫系统。本研究结果为膳食来源小RNA的选择性吸收提供了证据，未来仍需开展相关研究以阐明膳食来源miRNA的转移机制。