Objectives MicroRNA (miRNA) profiles have been evaluated in several biospecimens in relation to common diseases for which diet may have a considerable impact. We aimed at characterising how specific diets are associated with the miRNome in stool of vegans, vegetarians and omnivores and how this is reflected in the gut microbial composition, as this is still poorly explored.
Design We performed small RNA and shotgun metagenomic sequencing in faecal samples and dietary recording from 120 healthy volunteers, equally distributed for the different diets and matched for sex and age.
Results We found 49 miRNAs differentially expressed among vegans, vegetarians and omnivores (adj. p <0.05) and confirmed trends of expression levels of such miRNAs in vegans and vegetarians compared with an independent cohort of 45 omnivores. Two miRNAs related to lipid metabolism, miR-636 and miR-4739, were inversely correlated to the non-omnivorous diet duration, independently of subject age. Seventeen miRNAs correlated (|rho|>0.22, adj. p <0.05) with the estimated intake of nutrients, particularly animal proteins, phosphorus and, interestingly, lipids. In omnivores, higher Prevotella and Roseburia and lower Bacteroides abundances than in vegans and vegetarians were observed. Lipid metabolism-related miR-425-3p and miR-638 expression levels were associated with increased abundances of microbial species, such as Roseburia sp. CAG 182 and Akkermansia muciniphila, specific of different diets. An integrated analysis identified 25 miRNAs, 25 taxa and 7 dietary nutrients that clearly discriminated (area under the receiver operating characteristic curve=0.89) the three diets.
Conclusion Stool miRNA profiles are associated with specific diets and support the role of lipids as a driver of epigenetic changes and host-microbial molecular interactions in the gut.
- molecular genetics
- colonic microflora
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information. Raw data are available upon request to the corresponding author.
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ST, GF and FDF are joint first authors.
Twitter @nsegata, @rupensa, @BarbaraPardini1
BP, DE and AN contributed equally.
Contributors BP, ST and AN contributed to concept and design; BP, GF, RGP, SG, ST, VP and AN to collection and assembly of the data; BP, GF, ST, AF, FC and AN to small RNA-Seq data analyses and interpretation; DE, FDF, EP and NS to metagenomic data analyses and interpretation; ST, BP, GF, FC, DE, FDF and AN to manuscript writing; all authors gave final approval of the version.
Funding This work was supported by Fondazione Umberto Veronesi postdoctoral fellowships 2017 and 2018 (recipients, ST and BP), Compagnia di San Paolo Torino, Italy (to BP, AN, ST), Lega Italiana per La Lotta contro i Tumori (to FC, BP and AN), Fondazione CRT (grant number 2019-0450 to RGP) the European H2020 research project Oncobiome (Grant number 825410), and the COST action TRANSCOLONCAN (CA17118). DE laboratory received funding from the JPI HDHL-INTIMIC - Knowledge Platform of Food, Diet, Intestinal Microbiomics and Human Health (ID 790) grant and the PRIN2017 (20174FHBWR_005) grant by the Italian Ministry of University and Research.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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