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An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota
Published on: July 31, 2019
Modulation of faecal miRNAs highlights the preventive effects of a Mediterranean low-inflammatory dietary
Oscar Illescas1, Giulio Ferrero2, Antonino Belfiore3
1Molecular Epigenomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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.
Insights
A low-inflammatory Mediterranean diet altered gut microRNAs and gene expression in Familial Adenomatous Polyposis patients, potentially preventing cancer by targeting inflammation.
Area of Science:
- Gastroenterology and Oncology
- Molecular Biology
- Nutritional Science
Background:
- Dietary interventions are explored for cancer therapy.
- A pilot study in Familial Adenomatous Polyposis (FAP) showed a low-inflammatory Mediterranean diet reduced inflammation markers.
- This study investigates the diet's effect on gut microRNA (miRNA) and gene expression.
Purpose of the Study:
- To determine if a low-inflammatory Mediterranean diet modulates faecal miRNA and gene expression in the gut.
- To assess the impact of the diet on the miRNome and transcriptome in FAP patients.
Main Methods:
- Small RNA sequencing analyzed faecal miRNA changes at baseline, 3 months, and 6 months.
- RNA sequencing evaluated rectal mucosa and adenoma transcriptome changes at baseline and 6 months.
- In silico methods identified miRNA-gene interactions and analyzed miRNA targets.
Main Results:
- The diet modulated 29 faecal miRNAs, with effects persisting for 3 months post-intervention.
- Specific miRNAs correlated with diet adherence and inflammation markers (calprotectin).
- Seventy genes were differentially expressed between adenoma and normal tissue, normalizing after the diet; modulated miRNAs and genes targeted inflammatory pathways.
Conclusions:
- Faecal miRNAs modulated by the diet target inflammation-related genes.
- Diet-induced changes in miRNA and gene expression with oncogenic/tumor suppressor functions suggest a cancer-preventive role for the Mediterranean diet.
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