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. 2021 Jan 14:11:619200.
doi: 10.3389/fphar.2020.619200. eCollection 2020.

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits

Affiliations

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits

Giulio Ferrero et al. Front Pharmacol. .

Abstract

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, p-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 (p-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.

Keywords: circulating miRNA; dietary habits; dietary natural compounds; plasma metabolites; sodium; vitamin D; vitamin E.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Schematic diagram of the study design. (B) Box plot showing the average Spearman correlation values computed between miRNA expression levels and the estimated intake of different Natural Compounds (NCs). (C) Network representation of the identified significant interactions between miRNAs and NCs. Each white node represents a miRNA; red, green, and blue nodes represent lipid-related, micro-element, or vitamin-related NCs, respectively. The size of the node is proportional to the node total degree. Each edge represents a statistically significant miRNA-NC correlation (p-value < 0.05 in at least two dietary groups). The correlation value is represented as the edge color while the edge width represents the absolute correlation coefficient. Dotted edges represent the miRNA-NC interactions significant also in the GLM analysis.
FIGURE 2
FIGURE 2
Scatterplot reporting the most significant NC-miRNA correlations for each NC class with a progressive increment or decrement in absolute correlation value in the three dietary groups. A color-code is used to distinguish subjects from each dietary group and the corresponding linear regression line is reported.
FIGURE 3
FIGURE 3
Bar plot reporting the 15 top significant Gene Ontology (GO) Biological Processes enriched in the target genes of plasmatic miRNAs resulting downregulated (in blue) or upregulated (in red) between subjects characterized by a higher or lower estimated intake of (from the top left corner in clockwise order) cholesterol, vitamin D, sodium, or vitamin E.

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References

    1. Ameling S., Kacprowski T., Chilukoti R. K., Malsch C., Liebscher V., Suhre K., et al. (2015). Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study. BMC Med. Genom. 8, 61 10.1186/s12920-015-0136-7 - DOI - PMC - PubMed
    1. Beckett E. L., Martin C., Duesing K., Jones P., Furst J., Yates Z., et al. (2014). Vitamin D receptor genotype modulates the correlation between vitamin D and circulating levels of let-7a/b and vitamin D intake in an elderly cohort. J. Nutrigenet. Nutrigenomics 7, 264–273. 10.1159/000381676 - DOI - PubMed
    1. Biersack B. (2016). Current state of phenolic and terpenoidal dietary factors and natural products as non-coding RNA/microRNA modulators for improved cancer therapy and prevention. Non-coding RNA Res. 1, 12–34. - PMC - PubMed
    1. Briskin D., Wang P. Y., Bartel D. P. (2020). The biochemical basis for the cooperative action of microRNAs. Proc. Natl. Acad. Sci. U. S. A. 117, 17764–17774. 10.1073/pnas.1920404117 - DOI - PMC - PubMed
    1. Cade J. E., Burley V. J., Warm D. L., Thompson R. L., Margetts B. M. (2004). Food-frequency questionnaires: a review of their design, validation and utilisation. Nutr. Res. Rev. 17, 5–22. 10.1079/NRR200370 - DOI - PubMed