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

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.

Stool microRNA profiles reflect different dietary and gut microbiome patterns in healthy individuals

“…This is consistent with previous observations in all the three dietary groups between the estimated intake of particular nutrients and a set of plasma miRNAs. 14 A rising number of available data support the modification of faecal miRNA levels as a proxy of alteration and response occurring in the gut epithelium. 84 Indeed, the main source of faecal miRNAs is represented by intestinal epithelial cells, as described by Liu et al 23 Although, in the present study, we did not assess the cell of origins of the detected miRNAs, the analysis of the TissueAtlas and Roadmap Epigenomics data confirmed that most of the stool DEmiRNAs identified in the present study are expressed and active in the gut.…”

“…13 Recently, we clarified certain relationships between specific miRNA expression and the inclusion of specific nutrients in the diets of healthy individuals. 14 Dietary components can modulate the composition and function of the gut microbiome 15 16 and diets rich in fibres and poor in animal-based products (VN/VT regimes, Mediterranean diet) may drive a selection of specific taxa. [17][18][19] In parallel, a growing number of studies reported the association of a gut microbiome dysbiosis with several gastrointestinal and non-gastrointestinal diseases, including diabetes, 20 inflammatory bowel disease 21 and cancer.…”

“… 13 Recently, we clarified certain relationships between specific miRNA expression and the inclusion of specific nutrients in the diets of healthy individuals. 14 …”

An Insight into miR-1290: An Oncogenic miRNA with Diagnostic Potential

“…Furthermore, the intake of specific nutrients such as sodium and vitamins D and E is related to circulating miRNA profiles in healthy subjects. Similarly, a diet rich in polyphenols (resveratrol, ellagitannins, ellagic acid, epigallocatechin-3-gallate, genistein, curcumin, diindolylomethane) that maintains human health by tumor-protective and cancer-suppressive effects, and the high consumption of dietary fatty acids are associated with metabolic diseases via the regulation of miRNA expression [75][76][77]. In addition to dietary habits, the type of physical activity is significant, since it is known that long-term exercise alters plasma miRNAs levels in healthy young women.…”

Impact of Fresh Table Grape Intake on Circulating microRNAs Levels in Healthy Subjects: A Significant Modulation of Gastrointestinal Cancer‐Related Pathways

“…In single or as clusters, dietary components can modulate miRNAs expression levels involved in regulating both physiological and pathological processes. [ 12 ] Different in vitro studies have been carried out to evaluate single nutrients' ability to affect miRNAs expression. [ 13,14 ] Cione and colleagues reviewed the in vitro effect of some grape polyphenols such as quercetin, epigallocatechin gallate, and resveratrol on miRNAs expression involved in inflammation and cancer.…”