Inter‐Individual Variability in Insulin Response after Grape Pomace Supplementation in Subjects at High Cardiometabolic Risk: Role of Microbiota and miRNA

SCOPE Dietary polyphenols have shown promising effects in mechanistic and preclinical studies on the regulation of cardiometabolic alterations. Nevertheless, clinical trials have provided contradictory results, with a high inter-individual variability. This study explored the role of gut microbiota and microRNAs (miRNAs) as factors contributing to the inter-individual variability in polyphenol response. METHODS AND RESULTS 49 subjects with at least two factors of metabolic syndrome were divided between responders (n = 23) or non-responders (n = 26), depending on the variation rate in fasting insulin after supplementation with grape pomace (6 weeks). The populations of selected fecal bacteria were estimated from fecal DNA by quantitative real-time PCR (qPCR), while the microbial-derived short chain fatty acids (SCFAs) were measured in fecal samples by gas chromatography. MicroRNAs were analyzed by Next-Gen Sequencing (NGS) on a representative sample, followed by targeted miRNA analysis (qPCR). Responder subjects showed significantly lower (p<0.05) Prevotella and Firmicutes levels, and increased (p<0.05) miR-222 levels. CONCLUSION After evaluating the selected substrates for Prevotella and target genes of miR-222, these variations suggested that responders were those subjects who exhibited impaired glycaemic control. This study shows that fecal microbiota and miRNA expression may be related to inter-individual variability in clinical trials with polyphenols. This article is protected by copyright. All rights reserved.