Red raspberry (Rubus idaeus L.) contains a variety of polyphenols including anthocyanins and ellagitannins. Red raspberry polyphenols absorbed in different forms (parent compounds, degradants or microbial metabolites) are subject to xenobiotic metabolism in the intestine, liver, and/or kidney, forming methylate, glucuronide, and sulfate conjugated metabolites. Upon acute exposure, (poly)phenol/metabolite presence in the blood depends mainly on intestinal absorption, enterohepatic circulation, and metabolism by resident microbiota. However, chronic exposure to red raspberry polyphenols may alter metabolite patterns depending on adaptions in the xenobiotic machinery and/or microbiota composition. Understanding the metabolic fate of these compounds and their composition in different biological specimens relative to the exposure time/dose will aid in designing future health benefit studies, including the mechanism of action studies. The present exploratory study applied ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight (QTOF) and triple quadrupole (QQQ) mass spectrometries to characterize red raspberry polyphenols in fruit and then their appearance, including metabolites in human biological samples (plasma, urine and breast milk) after the chronic intake of red raspberries. The results suggested that the most abundant polyphenols in red raspberries included cyanidin 3-O-sophoroside, cyanidin 3-O-glucoside, sanguiin H6 and lambertianin C. Sixty-two (poly)phenolic compounds were tentatively identified in the plasma, urine and breast milk samples after the intake of red raspberries. In general, urine contained the highest content of phenolic metabolites; phase II metabolites, particularly sulfated conjugates, were mainly present in urine and breast milk, and breast milk contained fewer parent anthocyanins compared to urine and plasma.

Certain fruits, such as strawberries, may impart cardiometabolic benefits due to their phytochemical content. Study aims were to assess the effects of strawberry intake on cardiometabolic risk factors and vascular endothelial function in adults with moderate hypercholesterolemia. This study was a randomized, controlled, double-blinded, 2-arm, 2-period (4-wk/period) crossover trial. Adults (n = 34; male/female 1:1; mean ± SEM age, 53 ± 1 y; BMI, 31 ± 1 kg/m²; LDL cholesterol, 133 ± 3 mg/dL) were randomly allocated to 1 of 2 study sequences in a 1:1 ratio. Participants drank study beverages twice daily containing freeze-dried strawberry powder (2 × 25 g) or energy-, volume-matched control powder for 4 wk separated by a 4-wk washout. The primary outcome variable was the difference in fasting LDL cholesterol after 4-wk interventions. Secondary outcomes were metabolic markers, inflammation, quantitative (poly)phenolic metabolomics, flow-mediated dilation (FMD), and blood pressure (BP), with the latter (FMD, BP) also assessed acutely at 1 h and 2 h after a 50-g bolus strawberry or control beverage. Mixed-model analysis of repeated measures via PROC MIXED, PC-SAS was performed on primary and secondary outcome variables. LDL cholesterol did not differ after the 4-wk interventions (P > 0.05), nor did fasting total cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, FMD, or BP (all P > 0.05). Significant intervention-by-hour interaction for FMD (P = 0.03) and BP (P = 0.05) revealed increased FMD at 1 h after strawberry compared with control by 1.5 ± 0.38% (P = 0.0008) and attenuated systolic BP at 2 h by 3.1 ± 0.99 mmHg (P = 0.02). Select phenolic metabolites increased significantly (P < 0.05) in blood following strawberry consumption while others decreased, including 3-(4-methoxyphenyl)propanoic acid-3-O-glucuronide, which was significantly correlated with increased FMD (P < 0.05). Strawberries may improve vascular health, independent of other metabolic changes. The effect may be related to changes in microbial-derived phenolic metabolites after strawberry consumption influencing endothelial function. Data support inclusion of strawberries in a heart-healthy diet in adults with moderate hypercholesterolemia. This trial was registered at clinicaltrials.gov as NCT02612090.

Evidence suggests that the gut microbiota and cardiometabolic status are associated, suggesting dietary interventions that alter the microbiota may affect metabolic health. 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. 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 ClinicalTrials.gov, NCT03049631. 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). 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.

Background: Gut microbiota metabolize select dietary (poly)phenols to absorbable metabolites that exert biological effects important in metabolic health. Microbiota composition associated with health/disease status may affect its functional capacity to yield bioactive metabolites from dietary sources. Therefore, this study assessed gut microbiome composition and its related functional capacity to metabolize fruit (poly)phenols in individuals with prediabetes and insulin resistance (PreDM-IR, n = 26) compared to a metabolically healthy Reference group (n = 10). Methods: Shotgun sequencing was used to characterize gut microbiome composition. Targeted quantitative metabolomic analyses of plasma and urine collected over 24 h were used to assess microbial-derived metabolites in response to a (poly)phenol-rich raspberry test drink. Results: PreDM-IR compared to the Reference group: (1) enriched Blautia obeum and Blautia wexlerae and depleted Bacteroides dorei and Coprococcus eutactus. Akkermansia muciniphila and Bacteroides spp. were depleted in the lean PreDM-IR subset; and (2) impaired microbial catabolism of select (poly)phenols resulting in lower 3,8-dihydroxy-urolithin (urolithin A), phenyl-γ-valerolactones and various phenolic acids concentrations (p < 0.05). Controlling for obesity revealed relationships with microbial species that may serve as metagenomic markers of diabetes development and therapeutic targets. Conclusions: Data provide insight from multi-omics approaches to advance knowledge at the diet–gut–disease nexus serving as a platform for devising dietary strategies to improve metabolic health.

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 (0–24 h) 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.

Diets emphasizing unsaturated fat and high fiber are associated with reducing cardio-metabolic risk factors. Avocados are rich in mono- and poly-unsaturated fats and fiber. Assess replacement of carbohydrate energy with avocado energy for 12 weeks on glucose homeostasis and cardio-metabolic risk factors in self-selecting free-living adults with overweight or obesity and insulin resistance. In a single-center, randomized, 2-arm, controlled, 12-week parallel trial, adults [n = 93, male: female 39:54, mean ± SD age 42 ± 12 years, BMI 32.6 ± 3.9 kg/m2, homeostatic assessment for insulin resistance, 2.7 ± 1.7] were counseled to exchange avocado (AV) or control food (C, low-fat low-fiber energy-matched) for carbohydrate food in their usual diet for 12 weeks. The primary outcome was the change in Matsuda Insulin Sensitivity Index (MISI) after 12-week interventions. Secondary outcomes were changes in fasting and post-oral glucose tolerance test glycemic variables, fasting lipids, endothelial activation and inflammation markers. ASA24 dietary assessment tool captured weekly dietary intake. Intervention effects were mainly determined by analysis of covariance using PC-SAS, 9.4. Dietary total, mono- and poly-unsaturated fat, fiber, and vegetable intake were higher in the AV group compared to C group (P < 0.05), and no change in body weight or composition was observed (P > 0.05). Differences between the changes in MISI after AV compared to C were not different (Δ0–12 week, P = 0.1092). Differences in fasting insulin (Δ0–12 week, P = 0.0855) and improved HbA1c (Δ0–12 week P = 0.0632) after AV vs C were suggested. C-reactive protein was significantly lower after AV vs C at 12 weeks (P = 0.0418). Select biomarkers of endothelial activation and lipoproteins by NMR were also influenced by AV vs C food intake. Avocado intake was associated with a healthier dietary pattern and trends favoring improved glucose control and reduced biomarkers of cardiometabolic risk when replacing avocado energy for carbohydrate energy in free-living adults with overweight or obesity and insulin resistance.