Plasma and Urinary (Poly)phenolic Profiles after 4-Week Red Raspberry (Rubus idaeus L.) Intake with or without Fructo-Oligosaccharide Supplementation

Abstract

Red raspberries (RRB) are high in anthocyanin- and ellagitannin- type (poly)phenols. This study aimed to investigate the effect of 4-week RRB supplementation on (poly)phenolic metabolism in adults with prediabetes and insulin-resistance (PreDM-IR); and whether adding fructo-oligosaccharides (FOS), prebiotics, would augment the microbial metabolites of RRB (poly)phenols. In a randomized crossover clinical trial, subjects (n = 35: PreDM-IR, n = 25; healthy Reference group, n = 10) consumed 1 cup RRB (fresh weight equivalence) per day and RRB with 8 g FOS per day each for 4 weeks in random order separated by 4-week washout. Plasma and urinary (poly)phenolic metabolites were characterized after (0–24h) consuming a RRB-based test drink (2 cups RRB) at baseline/week 0 and again after 4-week supplementations. A total of 123 (poly)phenolic metabolites were quantified. After 4-week RRB supplementation, several metabolite groups were significantly increased (p < 0.05), including urolithins, phenyl-γ-valerolactones, and phenolic acids. Supplementing FOS with RRB for 4 weeks enhanced benzoic acid derivatives compared to the baseline (p < 0.05). Specific effects of supplementation by metabolic status indicated 4-week RRB supplementation significantly increased microbial metabolites that were lower in PreDM-IR group. Our results suggest alterations in the capacity of PreDM-IR group to metabolize and render bioavailable raspberry-derived (poly)phenols when consumed regularly.

Functional Deficits in Gut Microbiome of Young and Middle-Aged Adults with Prediabetes Apparent in Metabolizing Bioactive (Poly)phenols

“…Urolithins (3,8-dihydroxy-urolithin, 3-hydroxy-urolithin and 3,9-dihydroxy-urolithin: urolithin A, urolithin B and isourolithin A, respectively) are final microbial metabolites of ellagic acids and ellagitannins, which accounted for 30% of total RRB (poly)phenols in the RRBtest drink [ 31 ]. Gordonibacter urolithinfaciens and Gordonibacter pamelaeae have been identified as capable of producing intermediate urolithins (i.e., 3,8,9-trihydroxy-urolithin, urolithin C) [ 48 ].…”

“…Phenyl- γ -valerolactones are microbial metabolites of flavan-3-ols, which accounted for 6% of (poly)phenols in the RRBtest drink [ 31 ]. The plasma AUC 0–24 h of phenyl- γ -valerolactones was not significantly different between the PreDM-IR and Reference groups ( Figure 5 b); however, the PreDM-IR group had significantly lower urinary excretion of phenyl- γ -valerolactones compared to the Reference group ( Figure 6 b).…”

“…Anthocyanins comprise a significant portion (~60%) of RRB (poly)phenols [ 31 ]. Unabsorbed anthocyanins are metabolized to various phenolic acids by gut microbiota, contributing to the total phenolic pool.…”

“…The plasma and urinary analysis of (poly)phenolic metabolites was performed using an ultra-high performance liquid chromatography triple quadrupole (UHPLC-QQQ) model 6460 (Agilent Technologies) as previously described [ 12 , 31 ]. Plasma samples were extracted using solid-phase extraction (SPE) C18 cartridges (3 mL et al, 200 mg; Agilent Technologies).…”

“…Metabolite identification was performed by multiple reaction monitoring (MRM) optimized with pure standards wherever possible and parent/daughter ion fragments obtained from an UHPLC coupled with quadruple time-of-flight (UHPLC-QTOF) [ 12 ]. Method validation and MRM ion transitions for different metabolites have been reported in our recently published work [ 31 ]. Nomenclature of (poly)phenolic metabolites is based on recent recommendations [ 32 ].…”