Red Raspberry and Fructo-Oligosaccharide Supplementation, Metabolic Biomarkers, and the Gut Microbiota in Adults with Prediabetes: A Randomized Crossover Clinical Trial

J Nutr. 2022 Jun 9;152(6):1438-1449. doi: 10.1093/jn/nxac037.


Background: Evidence suggests that the gut microbiota and cardiometabolic status are associated, suggesting dietary interventions that alter the microbiota may affect metabolic health.

Objectives: We investigated whether supplementation with (poly)phenol-dense red raspberries (RRB), alone or with a fructo-oligosaccharide (FOS) prebiotic, would improve biomarkers of cardiometabolic risk in individuals with prediabetes (PreDM) and insulin resistance (IR) and whether the effects are related to modulation of the gut microbiota.

Methods: Adults with PreDM-IR (n = 26; mean ± SEM age, 35 ± 2 years; fasting glucose, 5.7 ± 0.1 mmol/L; HOMA-IR, 3.3 ± 0.3) or who were metabolically healthy (reference group; n = 10; age, 31 ± 3 years; fasting glucose, 5.1 ± 0.2 mmol/L; HOMA-IR, 1.1 ± 0.1) participated in a randomized crossover trial with two 4-week supplementation periods, in which they consumed either RRB (125 g fresh equivalents) daily or RRB + 8g FOS daily, separated by a 4-week washout. The primary outcome variable was the change in the gut microbiota composition, assessed by shotgun sequencing before (baseline) and at the end of each supplementation period. Secondary outcomes were changes in glucoregulation, lipid metabolism, anti-inflammatory status, and anthropometry. The trial is registered at, NCT03049631.

Results: In PreDM-IR, RRB supplementation reduced hepatic-IR (-30.1% ± 14.6%; P = 0.04) and reduced plasma total and LDL cholesterol [-4.9% ± 1.8% (P = 0.04) and -7.2% ± 2.3% (P = 0.003), respectively] from baseline. Adding FOS (RRB + FOS) improved β-cell function [insulin secretion rate, +70.2% ± 32.8% (P = 0.02); Disposition Index, +94.4% ± 50.2% (P = 0.04)], but had no significant effect on plasma cholesterol compared to baseline. RRB increased Eubacterium eligens (2-fold) and decreased Ruminococcus gnavus (-60% ± 34%), whereas RRB + FOS increased Bifidobacterium spp. (4-fold) and decreased Blautia wexlerae (-23% ± 12%) from baseline (all P values ≤ 0.05). R. gnavus was positively correlated with hepatic-IR, and E. eligens and Bifidobacterium catenulatum were negatively correlated with cholesterol concentrations (P ≤ 0.05).

Conclusions: Increased Bifidobacterium spp., concurrently with reduced R. gnavus, was associated with metabolic improvements in adults with PreDM-IR, warranting further research on the mechanisms involved in (poly)phenol/FOS-microbial interactions with host metabolism.

Keywords: fructo-oligosaccharide; gut microbiota; metabolic health; prediabetes; red raspberry.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Cardiovascular Diseases*
  • Cholesterol
  • Cross-Over Studies
  • Gastrointestinal Microbiome*
  • Glucose
  • Humans
  • Insulin Resistance*
  • Oligosaccharides / pharmacology
  • Oligosaccharides / therapeutic use
  • Phenols
  • Prebiotics
  • Prediabetic State*
  • Rubus*


  • Biomarkers
  • Oligosaccharides
  • Phenols
  • Prebiotics
  • Cholesterol
  • Glucose

Associated data