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

Abstract

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 high inter-individual variability. This study explores 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 are divided between responders (n = 23) or non-responders (n = 26), depending on the variation rate in fasting insulin after grape pomace supplementation (6 weeks). The populations of selected fecal bacteria are estimated from fecal deoxyribonucleic acid (DNA) by quantitative real-time polymerase chain reaction (qPCR), while the microbial-derived short-chain fatty acids (SCFAs) are measured in fecal samples by gas chromatography. MicroRNAs are analyzed on a representative sample, followed by targeted miRNA analysis. Responder subjects show 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 suggest that responders are those subjects exhibiting impaired glycaemic control. This study shows that fecal microbiota and miRNA expression may be related to inter-individual variability in clinical trials with polyphenols.

Keywords: grape pomace; insulin response; miRNA; microbiota.