Ferrero Giulio, Carpi Sara, Polini Beatrice, Pardini Barbara, Nieri Paola, Impeduglia Alessia, Grioni Sara, Tarallo Sonia, Naccarati Alessio
Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
Department of Computer Science, University of Turin, Torino, Italy.
Front Pharmacol. 2021 Jan 14;11:619200. doi: 10.3389/fphar.2020.619200. eCollection 2020.
Diet has a strong influence on many physiological processes, which in turn have important implications on a variety of pathological conditions. In this respect, microRNAs (miRNAs), a class of small non-coding RNAs playing a relevant epigenetic role in controlling gene expression, may represent mediators between the dietary intake and the healthy status. Despite great advances in the field of nutri-epigenomics, it remains unclear how miRNA expression is modulated by the diet and, specifically, the intake of specific nutrients. We investigated the whole circulating miRNome by small RNA-sequencing performed on plasma samples of 120 healthy volunteers with different dietary habits (vegans, vegetarians, and omnivores). Dietary intakes of specific nutrients were estimated for each subject from the information reported in the food-frequency questionnaire previously validated in the EPIC study. We focused hereby on the intake of 23 natural compounds (NCs) of the classes of lipids, micro-elements, and vitamins. We identified 78 significant correlations (rho > 0.300, -value < 0.05) among the estimated daily intake of 13 NCs and the expression levels of 58 plasma miRNAs. Overall, vitamin D, sodium, and vitamin E correlated with the largest number of miRNAs. All the identified correlations were consistent among the three dietary groups and 22 of them were confirmed as significant (-value < 0.05) by age-, gender-, and body-mass index-adjusted Generalized Linear regression Model analysis. miR-23a-3p expression levels were related with different NCs including a significant positive correlation with sodium (rho = 0.377) and significant negative correlations with lipid-related NCs and vitamin E. Conversely, the estimated intake of vitamin D was negatively correlated with the expression of the highest number of circulating miRNAs, particularly miR-1277-5p (rho = -0.393) and miR-144-3p (rho = -0.393). Functional analysis of the targets of sodium intake-correlated miRNAs highlighted terms related to cardiac development. A similar approach on targets of those miRNAs correlated with vitamin D intake showed an enrichment in genes involved in hormone metabolisms, while the response to chronic inflammation was among the top enriched processes involving targets of miRNAs negatively related with vitamin E intake. Our findings show that nutrients through the habitual diet influence circulating miRNA profiles and highlight that this aspect must be considered in the nutri-epigenomic research.
饮食对许多生理过程有强烈影响，而这些生理过程反过来又对多种病理状况具有重要意义。在这方面，微小RNA（miRNA）作为一类在控制基因表达中发挥重要表观遗传作用的小型非编码RNA，可能是饮食摄入与健康状况之间的介质。尽管营养表观基因组学领域取得了巨大进展，但目前仍不清楚饮食，特别是特定营养素的摄入如何调节miRNA的表达。我们通过对120名具有不同饮食习惯（纯素食者、素食者和杂食者）的健康志愿者的血浆样本进行小RNA测序，研究了整个循环miRNome。根据先前在EPIC研究中验证的食物频率问卷中报告的信息，估算了每个受试者特定营养素的饮食摄入量。在此，我们重点关注了脂质、微量元素和维生素类别的23种天然化合物（NCs）的摄入量。我们在13种NCs的估计每日摄入量与58种血浆miRNA的表达水平之间鉴定出78种显著相关性（rho>0.300，p值<0.05）。总体而言，维生素D、钠和维生素E与最多数量的miRNA相关。所有鉴定出的相关性在三个饮食组中都是一致的，其中22种通过年龄、性别和体重指数调整的广义线性回归模型分析被确认为显著（p值<0.05）。miR-23a-3p的表达水平与不同的NCs相关，包括与钠呈显著正相关（rho = 0.377），与脂质相关的NCs和维生素E呈显著负相关。相反，维生素D的估计摄入量与循环miRNA中数量最多的miRNA的表达呈负相关，特别是miR-1277-5p（rho = -0.393）和miR-144-3p（rho = -0.393）。对与钠摄入量相关的miRNA的靶标的功能分析突出了与心脏发育相关的术语。对与维生素D摄入量相关的那些miRNA的靶标采用类似方法显示，参与激素代谢的基因富集，而对慢性炎症的反应是涉及与维生素E摄入量呈负相关的miRNA靶标的最富集过程之一。我们的研究结果表明，习惯性饮食中的营养素会影响循环miRNA谱，并强调在营养表观基因组学研究中必须考虑这一方面。
