Intestinal miRNAs regulated in response to dietary lipids

Gil-Zamorano, Judit; Tomé‐Carneiro, João; Hazas, María-Carmen López de Las; Pozo-Acebo, Lorena Del; Crespo, M. Carmen; Gómez-Coronado, Diego; Chapado, Luis A; Herrera, Emílio; Latasa, María-Jesús; Ruiz-Roso, María Belén; Castro-Camarero, Mónica; Briand, Olivier; Dávalos, Alberto

doi:10.1038/s41598-020-75751-w

Cited by 13 publications

(8 citation statements)

References 65 publications

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“…13 In this study, vegetable lipids were the nutrients associated with the highest number of stool DEmiRNAs, together with animal lipids (namely miR-425-3p, miR-638, miR-8063 and miR-4277), but the latter showed an opposite trend. This result is consistent with previous evidence on the activity of lipids in modulating miRNA expression in different tissues, including gut, 77 adipocytes, 78 and plasma. 79 A functional enrichment analysis was performed to identify the candidate downstream signalling and metabolic pathways that may be affected by an intestinal miRNA expression modulation, which is reflected in stool samples.…”

Section: Discussionsupporting

confidence: 93%

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

Tarallo

Ferrero

Filippis

et al. 2021

Gut

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ObjectivesMicroRNA (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.DesignWe 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.ResultsWe 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.ConclusionStool 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.

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Section: Discussionsupporting

confidence: 93%

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

Tarallo

Ferrero

Filippis

et al. 2021

Gut

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“…Some miRNAs appear to do this by affecting lipid metabolism in the small intestine. It has been shown, for instance, that mice with a small intestinal DICER-knock out display abnormal absorption and processing of lipids [ 31 , 32 ]. Lipid metabolism is also important in the maintenance of the regenerative capacity of the small intestinal crypt [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease

Barisani

Panceri

Modderman

et al. 2021

IJMS

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Celiac disease (CeD) is triggered by gluten and results in inflammation and villous atrophy of the small intestine. We aimed to explore the role of miRNA-mediated deregulation of the transcriptome in CeD. Duodenal biopsies of CeD patients (n = 33) and control subjects (n = 10) were available for miRNA-sequencing, with RNA-sequencing also available for controls (n = 5) and CeD (n = 6). Differential expression analysis was performed to select CeD-associated miRNAs and genes. MiRNA‒target transcript pairs selected from public databases that also displayed a strong negative expression correlation in the current dataset (R < −0.7) were used to construct a CeD miRNA‒target transcript interaction network. The network includes 2030 miRNA‒target transcript interactions, including 423 experimentally validated pairs. Pathway analysis found that interactions are involved in immune-related pathways (e.g., interferon signaling) and metabolic pathways (e.g., lipid metabolism). The network includes 13 genes previously prioritized to be causally deregulated by CeD-associated genomic variants, including STAT1. CeD-associated miRNAs might play a role in promoting inflammation and decreasing lipid metabolism in the small intestine, thereby contributing unbalanced cell turnover in the intestinal crypt. Some CeD-associated miRNAs deregulate genes that are also affected by genomic CeD-risk variants, adding an additional layer of complexity to the deregulated transcriptome in CeD.

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“…Small intestinal miRNA expression is significantly altered by high fat diet and excessive lipid exposure 43 , 44 . Furthermore, a study utilizing a mouse model of intestinal Dicer-1 knockout showed that disruption of intestinal miRNA expression results in changes to lipid absorption and accumulation 45 . Other studies have confirmed extensive regulation of lipid metabolism by intestinal miRNAs 46 .…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of dysregulated microRNA and mRNA expression in intestinal epithelial cells following ethanol intoxication and burn injury

Herrnreiter

Luck

et al. 2021

Sci Rep

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Gut barrier dysfunction is often implicated in pathology following alcohol intoxication and burn injury. MicroRNAs (miRNAs) are negative regulators of gene expression that play a central role in gut homeostasis, although their role after alcohol and burn injury is poorly understood. We performed an integrated analysis of miRNA and RNA sequencing data to identify a network of interactions within small intestinal epithelial cells (IECs) which could promote gut barrier disruption. Mice were gavaged with ~ 2.9 g/kg ethanol and four hours later given a ~ 12.5% TBSA full thickness scald injury. One day later, IECs were harvested and total RNA extracted for RNA-seq and miRNA-seq. RNA sequencing showed 712 differentially expressed genes (DEGs) (padj < 0.05) in IECs following alcohol and burn injury. Furthermore, miRNA sequencing revealed 17 differentially expressed miRNAs (DEMs) (padj < 0.1). Utilizing the miRNet, miRDB and TargetScan databases, we identified both validated and predicted miRNA gene targets. Integration of small RNA sequencing data with mRNA sequencing results identified correlated changes in miRNA and target expression. Upregulated miRNAs were associated with decreased proliferation (miR-98-3p and miR-381-3p) and cellular adhesion (miR-29a-3p, miR-429-3p and miR3535), while downregulated miRNAs were connected to upregulation of apoptosis (Let-7d-5p and miR-130b-5p) and metabolism (miR-674-3p and miR-185-5p). Overall, these findings suggest that alcohol and burn injury significantly alters the mRNA and miRNA expression profile of IECs and reveals numerous miRNA–mRNA interactions that regulate critical pathways for gut barrier function after alcohol and burn injury.

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Intestinal miRNAs regulated in response to dietary lipids

Cited by 13 publications

References 65 publications

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

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

A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease

Integrated analysis of dysregulated microRNA and mRNA expression in intestinal epithelial cells following ethanol intoxication and burn injury

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