Effect of a 12-Week Polyphenol Rutin Intervention on Markers of Pancreatic β-Cell Function and Gut Microbiota in Adults with Overweight without Diabetes

Abstract

Supplementation with prebiotic polyphenol rutin is a potential dietary therapy for type 2 diabetes prevention in adults with obesity, based on previous glycaemic improvement in transgenic mouse models. Gut microbiota are hypothesised to underpin these effects. We investigated the effect of rutin supplementation on pancreatic β-cell function measured as C-peptide/glucose ratio, and 16S rRNA gene-based gut microbiota profiles, in a cohort of individuals with overweight plus normoglycaemia or prediabetes. Eighty-seven participants were enrolled, aged 18-65 years with BMI of 23-35 kg/m². This was a 12-week double-blind randomised controlled trial (RCT), with 3 treatments comprising (i) placebo control, (ii) 500 mg/day encapsulated rutin, and (iii) 500 mg/day rutin-supplemented yoghurt. A 2-h oral glucose tolerance test (OGTT) was performed at baseline and at the end of the trial, with faecal samples also collected. Compliance with treatment was high (~90%), but rutin in both capsule and dietary format did not alter pancreatic β-cell response to OGTT over 12 weeks. Gut bacterial community composition also did not significantly change, with Firmicutes dominating irrespective of treatment. Fasting plasma glucose negatively correlated with the abundance of the butyrate producer Roseburia inulinivorans, known for its anti-inflammatory capacity. This is the first RCT to investigate postprandial pancreatic β-cell function in response to rutin supplementation.

Keywords: gut microbiota; pancreas β-cell function; prebiotic polyphenol rutin.

Figure 1

CONSORT flow chart for the rutin dietary intervention trial.

Figure 2

Post-OGTT comparison (mean ± SEM) of iAUC C-peptide/glucose ratio (A), iAUC glucose (D), iAUC insulin (G) and iAUC C-peptide (J) between health-associated cohorts for each of the three treatment groups (Control, placebo; RC, rutin capsule; RY, rutin yoghurt). Density plots showing variation in responses to treatment among health-associated cohorts are presented in panels (B,E,H,K). Change in respective iAUC parameters over time (CID 1 to CID 4) is presented in plots (C,F,I,L) (Mean ± SEM). * p-value < 0.05.

Figure 3

Phylum-level (top) and zOTU-level (bottom) gut bacterial community composition for all participants investigated from each study arm at CID 1 and CID 4. Each column on the graph represents data from a single participant. zOTUs with ≥1% overall 16S rRNA gene relative sequence abundance are shown, with all remaining zOTUs grouped together in “Other”. Control, placebo; RC, rutin capsule; RY, rutin yoghurt.