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.
Clin Nutr. 2024 Apr;43(4):951-959. doi: 10.1016/j.clnu.2024.02.023. Epub 2024 Feb 26.
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.
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.
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.
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.
NCT04552405, Registered in ClinicalTrials.gov.
饮食干预已被提议作为多种疾病（包括癌症）的治疗方法。一项针对家族性腺瘤性息肉病（FAP）患者的低炎症性地中海饮食干预研究表明，这种饮食可以降低局部和全身炎症标志物。我们旨在确定这种饮食是否可以调节肠道中的粪便 microRNA（miRNA）和基因表达。
在基线（T0）、三个月干预后（T1）和额外三个月后（T2），通过小 RNA 测序评估粪便 miRNA 组的变化。在 T0 和 T2 时，通过 RNA 测序评估健康直肠黏膜和腺瘤的转录组变化。使用计算方法鉴定验证 miRNA-基因相互作用，并对 miRNA 靶标的功能进行分析。
本研究共纳入 27 例患者。研究发现，该饮食可调节 29 种粪便 miRNA（p<0.01；|log2 Fold Change|>1），且这种调节作用在干预后三个月仍持续存在。miR-3612-3p 和 miR-941 的水平与饮食的依从性相关，miR-3670 和 miR-4252-5p 与粪便钙卫蛋白相关，miR-3670 和 miR-6867 与血清钙卫蛋白相关。腺瘤与正常组织之间有 70 个基因表达差异，且大多数基因在饮食干预前不同，但在饮食后达到相似水平。功能富集分析发现，促炎 ERK1/2、细胞周期调控和营养反应途径是受调节的 miRNA 和基因共同调控的。
饮食干预调节的粪便 miRNA 靶向参与炎症的基因。具有致癌和肿瘤抑制功能的 miRNA 和基因水平的变化进一步支持低炎症性地中海饮食的潜在抗癌作用。
NCT04552405，在 ClinicalTrials.gov 注册。
