Modulation of faecal miRNAs highlights the preventive effects of a Mediterranean low-inflammatory dietary intervention.

Manuela Gariboldi, Chiara M Ciniselli, Alessio Naccarati, Sonia Tarallo, Barbara Pardini, Giulio Ferrero, Antonino Belfiore, Patrizia Pasanisi, Elena Daveri, Sara Noci, Oscar Illescas, Licia Rivoltini, Daniele Morelli, Andrea Mancini, Massimo Milione, Paolo Verderio, Laura Cattaneo, Marco Vitellaro, Stefano Signoroni, Francesca Cordero

Journal: Clinical nutrition (Edinburgh, Scotland) 2024;43(4):951-959

PMID: 38422953

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP), reduced markers of local and systemic inflammation. We aim to determine whether this diet may modulate faecal microRNA (miRNA) and gene expression in the gut.

METHODS

Changes in the faecal miRNome were evaluated by small RNA sequencing at baseline (T0), after the three-month intervention (T1), and after an additional three months (T2). Changes in the transcriptome of healthy rectal mucosa and adenomas were evaluated by RNA sequencing at T0 and T2. The identification of validated miRNA-gene interactions and functional analysis of miRNA targets were performed using in silico approaches.

RESULTS

Twenty-seven subjects were included in this study. It was observed that the diet modulated 29 faecal miRNAs (p < 0.01; |log2 Fold Change|>1), and this modulation persisted for three months after the intervention. Levels of miR-3612-3p and miR-941 correlated with the adherence to the diet, miR-3670 and miR-4252-5p with faecal calprotectin, and miR-3670 and miR-6867 with serum calprotectin. Seventy genes were differentially expressed between adenoma and normal tissue, and most were different before the dietary intervention but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation, and nutrient response pathways as commonly regulated by the modulated miRNAs and genes.

CONCLUSIONS

Faecal miRNAs modulated by the dietary intervention target genes that participate in inflammation. Changes in levels of miRNAs and genes with oncogenic and tumour suppressor functions further support the potential cancer-preventive effect of the low-inflammatory Mediterranean diet.

CLINICAL TRIAL NUMBER REGISTRATION

NCT04552405, Registered in ClinicalTrials.gov.

Address: Molecular Epigenomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Dept. of Clinical and Biological Sciences, University of Turin, Turin, Italy; Dept. of Computer Science, University of Turin, Turin, Italy.; First Pathology Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Turin, Italy; Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.; Bioinformatics and Biostatistics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Diagnostic and Therapeutic Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Laboratory Medicine Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Unit of Epidemiology and Prevention, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Molecular Epigenomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: [email protected].

DOI: 10.1016/j.clnu.2024.02.023