Data on microRNA expression, predicted gene targets and pathway analysis in response to different concentrations of a cranberry proanthocyanidin-rich extract and its metabolite 3-(4-hydroxyphenyl)-propionic acid in intestinal Caco-2BBe1 cells.

Cranberry-derived proanthocyanidin (PAC) is processed by the gut microbiota to produce 3-(4-hydroxyphenyl)-propionic acid (HPPA), among other metabolites. These data are in support of the article entitled, "Cranberry proanthocyanidin and its microbial metabolite 3,4-dihydroxyphenylacetic acid, but not 3-(4-hydroxyphenyl)-propionic acid, partially reverse pro-inflammatory microRNA responses in human intestinal epithelial cells," published in Molecular Nutrition and Food Research [1]. Here we describe data generated by nCounterⓇ Human v3 miRNA Expression Panel of RNA obtained from Caco-2BBe1 cells exposed to two different concentrations of cranberry extract rich in PAC (50 µg/ml or 100 µg/ml) or 3-(4-hydroxyphenyl)-propionic acid (5 µg/ml or 10 µg/ml) for 24 h, then stimulated with 1 ng/ml of IL-1ß or not (mock) for three hours. The raw data are publicly available at the NCBI GEO database GSE237078. This work also includes descriptive methodological procedures, treatment-responsive microRNA (miRNA) expression profiles in Caco-2BBe1 cells, and in silico mRNA gene target and pathway enrichment analyses of significantly differentially expressed miRNAs (q < 0.001). Cranberry and its components have recognized health benefits, particularly in relation to combatting inflammation and pathogenic bacterial adhesion. These data will be valuable as a reference to study the response of intestinal cells to other polyphenol-rich food sources, analyze gut microbial responses to cranberry and its metabolites in different cell lines and mammalian hosts to elucidate individualized effects, and to delineate the role of the gut microbiota in facilitating the benefits of cranberry. Moreover, these data will aid in expanding our knowledge on the mechanisms underlying the benefits of cranberry and its components.

Food Intake Suppresses ApoB Secretion and Fractional Catabolic Rates in Humans.

BACKGROUND: Humans spend much of the day in the postprandial state. However, most research and clinical guidelines on plasma lipids pertain to blood drawn after a 12-hour fast. We aimed to study the metabolic differences of apoB lipoproteins between the fasting and postprandial states. METHODS: We investigated plasma apoB metabolism using stable isotope tracers in 12 adult volunteers under fasting and continuous postprandial conditions in a randomized crossover study. We determined the metabolism of apoB in multiple lipoprotein subfractions, including light and dense VLDLs (very-low-density lipoproteins), IDLs (intermediate-density lipoproteins), and light and dense LDLs (low-density lipoproteins) that do or do not contain apoE or apoC3. RESULTS: A major feature of the postprandial state is 50% lower secretion rate of triglyceride-rich lipoproteins and concurrent slowdown of their catabolism in circulation, as shown by 34% to 55% lower rate constants for the metabolic pathways of conversion by lipolysis from larger to smaller lipoproteins and direct clearance of lipoproteins from the circulation. In addition, the secretion pattern of apoB lipoprotein phenotypes was shifted from particles containing apoE and apoC3 in the fasting state to those without either protein in the postprandial state. CONCLUSIONS: Overall, during the fasting state, hepatic apoB lipoprotein metabolism is activated, characterized by increased production, transport, and clearance. After food intake, endogenous apoB lipoprotein metabolism is globally reduced as appropriate to balance dietary input to maintain the supply of energy to peripheral tissues.

Impact of a rapid access chest pain clinic in Singapore to improve evaluation of new-onset chest pain.

BACKGROUND: Chest pain (CP) accounts for 5% of emergency department (ED) visits, unplanned hospitalisations and costly admissions. Conversely, outpatient evaluation requires multiple hospital visits and longer time to complete testing. Rapid access chest pain clinics (RACPCS) are established in the UK for timely, cost-effective CP assessment. This study aims to evaluate the feasibility, safety, clinical and economic benefits of a nurse-led RACPC in a multiethnic Asian country. METHODS: Consecutive CP patients referred from a polyclinic to the local general hospital were recruited. Referring physicians were left to their discretion to refer patients to the ED, RACPC (launched in April 2019) or outpatients. Patient demographics, diagnostic journey, clinical outcomes, costs, HEART (History, ECG, Age, Risk Factors, Troponin) scores and 1-year overall mortality were recorded. RESULTS: 577 CP patients (median HEAR score of 2.0) were referred; 237 before the launch of RACPC. Post RACPC, fewer patients were referred to the ED (46.5% vs 73.9%, p < 0.01), decreased adjusted bed days for CP, more non-invasive tests (46.8 vs 39.2 per 100 referrals, p = 0.07) and fewer invasive coronary angiograms (5.6 vs 12.2 per 100 referrals, p < 0.01) were performed. Time from referral to diagnosis was shortened by 90%, while requiring 66% less visits (p < 0.01). System cost to evaluate CP was reduced by 20.7% and all RACPC patients were alive at 12 months. CONCLUSIONS: An Asian nurse-led RACPC expedited specialist evaluation of CP with less visits, reduced ED attendances and invasive testing whilst saving costs. Wider implementation across Asia would significantly improve CP evaluation.

Predictive models built upon annotated and validated intake biomarkers in urine using paired or unpaired analysis helped to classify cranberry juice consumers in a randomized, double-blinded, placebo-controlled, and crossover study.

Intake biomarkers of cranberry juice in women can assess consumption in clinical trials. Discriminant biomarkers in urine may explain urinary tract infection (UTI) preventive activities. We hypothesized that validated and annotated discriminant metabolites in human urine could be used as intake biomarkers in building predictive multivariate models to classify cranberry consumers. Urine samples were collected from 16 healthy women aged 18 to 29 years at baseline and after 3- and 21-day consumption of cranberry or placebo juice in a double-blind, crossover study. Urine metabolomes were analyzed using ultra high-performance liquid chromatography coupled with Orbitrap mass spectrometry. Paired and unpaired multivariate analyses were used to annotate or identify discriminant metabolic features after cranberry consumption. Twenty-six discriminant metabolic features (paired analysis) and 27 (unpaired analysis) after cranberry consumption in an open-label intervention were rediscovered in the blinded study. These metabolites included exogenous (quinic acid) and endogenous ones (hippuric acid). The paired analysis showed better model fitting with partial least-square discriminant analysis models built on all metabolites than the unpaired analysis. Predictive models built on shared metabolites by the unpaired analysis were able to classify cranberry juice consumers with 84.4% to 100% correction rates, overall better than the paired analysis (50%-100%). The double-blind study validated discriminant metabolites from a previous open-label study. These urinary metabolites may be associated with the ability of cranberries to prevent UTIs and serve as potential cranberry intake biomarkers. It reveals the importance of selecting the right predictive models to classify cranberry consumers with higher than 95% correction rates.

Cranberry Juice Polyphenols Inhibited the Formation of Advanced Glycation End Products in Collagens, Inhibited Advanced Glycation End Product-Induced Collagen Crosslinking, and Cleaved the Formed Crosslinks.

Collagens in the human skin are susceptible to glycation due to their long half-life of about 15 years, accumulating advanced glycation end products (AGEs). The formation of AGEs and the subsequent AGE-induced collagen crosslinking are major factors for skin aging. The objective of this study was to determine the capacity of cranberry juice polyphenols (CJPs) and their fractions to inhibit collagen glycation and to break AGE-induced crosslinks in collagens. Concentrated cranberry juice was extracted to obtain the CJP, which was further fractionated into an ethyl acetate fraction, water fraction, 30% methanol (MeOH) fraction, 60% MeOH fraction, MeOH fraction, and acetone fraction. CJPs and their fractions contained different ratios of anthocyanins, procyanidins, and flavonols. All the fractions significantly inhibited collagen glycation assessed with the collagen-methylglyoxal (MGO) or collagen-dehydroascorbic acid (DHAA) assays. The ethyl acetate fraction and 60% MeOH had the lowest IC50 values in the collagen-MGO and collagen-DHAA assays. The methanol fraction (IC50 = 0.52 µg/mL) and acetone fraction (IC50 = 0.019 mg/mL) had the lowest IC50 values in the inhibition and breakage of AGE-induced collagen crosslinking, respectively. The ethyl acetate fraction significantly scavenged the highest amount of MGO and DHAA after incubation compared to the other fractions. Results suggested that procyanidins were the most effective antiglycation agent in both collagen glycation assays, followed by flavonols and anthocyanins. High-performance liquid chromatography-electrospray ionization─tandem mass spectrometry showed that the reactions of DHAA with quercetin or epicatechin formed several adducts with unreported proposed structures. This study suggested that CJPs may be used as active ingredients in cosmetics to prevent skin collagen glycation and crosslinking and to break the formed crosslinks.

Cranberry Arabino-Xyloglucan and Pectic Oligosaccharides Induce Lactobacillus Growth and Short-Chain Fatty Acid Production.

Numerous health benefits have been reported from the consumption of cranberry-derived products, and recent studies have identified bioactive polysaccharides and oligosaccharides from cranberry pomace. This study aimed to further characterize xyloglucan and pectic oligosaccharide structures from pectinase-treated cranberry pomace and measure the growth and short-chain fatty acid production of 86 Lactobacillus strains using a cranberry oligosaccharide fraction as the carbon source. In addition to arabino-xyloglucan structures, cranberry oligosaccharides included pectic rhamnogalacturonan I which was methyl-esterified, acetylated and contained arabino-galacto-oligosaccharide side chains and a 4,5-unsaturated function at the non-reducing end. When grown on cranberry oligosaccharides, ten Lactobacillus strains reached a final culture density (ΔOD) ≥ 0.50 after 24 h incubation at 32 °C, which was comparable to L. plantarum ATCC BAA 793. All strains produced lactic, acetic, and propionic acids, and all but three strains produced butyric acid. This study demonstrated that the ability to metabolize cranberry oligosaccharides is Lactobacillus strain specific, with some strains having the potential to be probiotics, and for the first time showed these ten strains were capable of growth on this carbon source. The novel cranberry pectic and arabino-xyloglucan oligosaccharide structures reported here combined with the Lactobacillus strains that can metabolize cranberry oligosaccharides and produce short-chain fatty acids, have excellent potential as health-promoting synbiotics.

A Freeze-Dried Cranberry Powder Consistently Enhances SCFA Production and Lowers Abundance of Opportunistic Pathogens In Vitro.

The American cranberry, Vaccinium macrocarpon, contains fibers and (poly)phenols that could exert health-promoting effects through modulation of gut microbiota. This study aimed to investigate how a freeze-dried whole cranberry powder (FCP) modulated metabolite production and microbial composition using both a 48-h incubation strategy and a long-term human gut simulator study with the M-SHIME (Mucosal Simulator of the Human Intestinal Microbial Ecosystem). FCP was repeatedly administered over three weeks. The studies included five and three study subjects, respectively. In both models, FCP significantly increased levels of health-related short-chain fatty acids (SCFA: acetate, propionate and butyrate), while decreased levels of branched-chain fatty acids (markers of proteolytic fermentation). Interestingly, FCP consistently increased luminal Bacteroidetes abundances in the proximal colon of the M-SHIME (+17.5 ± 9.3%) at the expense of Proteobacteria (-10.2 ± 1.5%). At family level, this was due to the stimulation of Bacteroidaceae and Prevotellaceae and a decrease of Pseudomonodaceae and Enterobacteriaceae. Despite of interpersonal differences, FCP also increased the abundance of families of known butyrate producers. Overall, FCP displayed an interesting prebiotic potential in vitro given its selective utilization by host microorganisms and potential health-related effects on inhibition of pathogens and selective stimulation of beneficial metabolites.

Cranberry Proanthocyanidin and Its Microbial Metabolite 3,4-Dihydroxyphenylacetic Acid, but Not 3-(4-Hydroxyphenyl)-Propionic Acid, Partially Reverse Pro-Inflammatory microRNA Responses in Human Intestinal Epithelial Cells.

SCOPE: The molecular basis underlying the anti-inflammatory and anticarcinogenic properties of cranberries is incompletely understood. The effects of a cranberry proanthocyanidin-rich extract (PAC) and two of its gut microbial metabolites, 3,4-dihydroxyphenylacetic acid (DHPAA) and 3-(4-hydroxyphenyl)-propionic acid (HPPA), on intestinal epithelial cells microRNA (miRNA) expression and their downstream pathways at homeostasis and in inflammatory conditions, are investigated. METHODS AND RESULTS: The expression of 799 miRNAs is quantitatively assessed in differentiated Caco-2BBe1 cells pre-treated with PAC, DHPAA, or HPPA and stimulated with interleukin (IL)-1ß or not. PAC, DHPAA, and HPPA generate subsets of shared and distinct miRNA responses. At homeostasis, miRNAs affected by the metabolites, but not PAC, targeted genes enriched in kinase, Wnt, and growth factor signaling, cell growth and proliferation, apoptosis, and specific cancer pathways. In an inflammatory environment, PAC and DHPAA, but not HPPA, reverses the expression of 16 and two IL-1ß-induced miRNAs, respectively, regulating inflammatory and cancer pathways. CONCLUSION: miRNA modulation is a novel mechanism for PAC bioactivity in the gut. The gut microbiota may be necessary to unlock these effects at homeostasis and partially in inflammation.

Simulated gastrointestinal digestion of cranberry polyphenols under dynamic conditions. Impact on antiadhesive activity against uropathogenic bacteria.

This study is the first dynamic simulation of gastrointestinal digestion of cranberry polyphenols [1 g cranberry extract per day (206.2 mg polyphenols) for 18 days]. Samples from the simulated ascending, transverse, and descending colon of the dynamic gastrointestinal simulator simgi® were analyzed. Results showed that 67% of the total cranberry polyphenols were recovered after simulated gastrointestinal digestion. Specifically, benzoic acids, hydroxycinnamic acids, phenylpropionic acids, phenylacetic acids, and simple phenols were identified. Cranberry feeding modified colonic microbiota composition of Enterococcaceae population significantly. However, increments in microbial-derived short-chain fatty acids, particularly in butyric acid, were observed. Finally, the simgi® effluent during cranberry feeding showed significant antiadhesive activity against uropathogenic Escherichia coli (13.7 ± 1.59 % of inhibition). Understanding the role that gut microbiota plays in cranberry metabolism could help to elucidate its interaction with the human body and explain cranberry protective effects against urinary tract infections.

A Cranberry Concentrate Decreases Adhesion and Invasion of Escherichia coli (AIEC) LF82 In Vitro.

While many beneficial host-microbiota interactions have been described, imbalanced microbiota in the gut is speculated to contribute to the progression and recurrence of chronic inflammatory diseases such as Crohn's disease (CD). This in vitro study evaluated the impact of a cranberry concentrate Type M (CTM) on adherent-invasive Escherichia coli (AIEC) LF82, a pathobiont associated with CD. Different stages of pathogenic infection were investigated: (i) colonization of the mucus layer, and (ii) adhesion to and (iii) invasion of the epithelial cells. Following 48 h of fecal batch incubation, 0.5 and 1 mM of CTM significantly altered AIEC LF82 levels in a simulated mucus layer, resulting in a decrease of 50.5% in the untreated blank, down to 43.0% and 11.4%, respectively. At 1 mM of CTM, the significant decrease in the levels of AIEC LF82 coincided with a stimulation of the metabolic activity of the background microbiota. The increased levels of health-associated acetate (+7.9 mM) and propionate levels (+3.5 mM) suggested selective utilization of CTM by host microorganisms. Furthermore, 1 mM of both fermented and unfermented CTM decreased the adhesion and invasion of human-derived epithelial Caco-2 cells by AIEC LF82. Altogether, this exploratory in vitro study demonstrates the prebiotic potential of CTM and supports its antipathogenic effects through direct and/or indirect modulation of the gut microbiome.

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs. RESULTS: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. CONCLUSION: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI. TRIAL REGISTRATION: Clinical trial registration number: ClinicalTrials.gov NCT01776021 .

Effect of daily consumption of cranberry beverage on insulin sensitivity and modification of cardiovascular risk factors in adults with obesity: a pilot, randomised, placebo-controlled study.

Cranberries are high in polyphenols, and epidemiological studies have shown that a high-polyphenol diet may reduce risk factors for diabetes and CVD. The present study aimed to determine if short-term cranberry beverage consumption would improve insulin sensitivity and other cardiovascular risk factors. Thirty-five individuals with obesity and with elevated fasting glucose or impaired glucose tolerance participated in a randomised, double-blind, placebo-controlled, parallel-designed pilot trial. Participants consumed 450 ml of low-energy cranberry beverage or placebo daily for 8 weeks. Changes in insulin sensitivity and cardiovascular risk factors including vascular reactivity, blood pressure, RMR, glucose tolerance, lipid profiles and oxidative stress biomarkers were evaluated. Change in insulin sensitivity via hyperinsulinaemic-euglycaemic clamp was not different between the two groups. Levels of 8-isoprostane (biomarker of lipid peroxidation) decreased in the cranberry group but increased in the placebo group (-2·18 v. +20·81 pg/ml; P = 0·02). When stratified by baseline C-reactive protein (CRP) levels, participants with high CRP levels (>4 mg/l) benefited more from cranberry consumption. In this group, significant differences in the mean change from baseline between the cranberry (n 10) and the placebo groups (n 7) in levels of TAG (-13·75 v. +10·32 %; P = 0·04), nitrate (+3·26 v. -6·28 µmol/l; P = 0·02) and 8-isoprostane (+0·32 v. +30·8 pg/ml; P = 0·05) were observed. These findings indicate that 8 weeks of daily cranberry beverage consumption may not impact insulin sensitivity but may be helpful in lowering TAG and changing certain oxidative stress biomarkers in individuals with obesity and a proinflammatory state.

Identifying Cranberry Juice Consumers with Predictive OPLS-DA Models of Plasma Metabolome and Validation of Cranberry Juice Intake Biomarkers in a Double-Blinded, Randomized, Placebo-Controlled, Cross-Over Study.

SCOPE: Methods to verify cranberry juice consumption are lacking. Predictive multivariate models built upon validated biomarkers may help to verify human consumption of a food using a nutrimetabolomics approach. METHODS: A 21-day double-blinded, randomized, placebo-controlled, cross-over study was conducted among healthy young women aged 1829. Plasma was collected at baseline and after 3-day and 21-day consumption of cranberry or placebo juice. Plasma metabolome was analyzed using UHPLC coupled with high resolution mass spectrometry. RESULTS: 18 discriminant metabolites in positive mode and 18 discriminant metabolites in negative mode from a previous 3-day open-label study were re-discovered in the present blinded study. Predictive orthogonal partial least squares discriminant analysis (OPLS-DA) models were able to identify cranberry juice consumers over a placebo juice group with 96.9% correction rates after 3-day consumption in both positive and negative mode. This present study revealed 84 and 109 additional discriminant metabolites in positive and negative mode, respectively. Twelve of them were tentatively identified. CONCLUSION: Cranberry juice consumers were classified with high correction rates using predictive OPLS-DA models built upon validated plasma biomarkers. Additional biomarkers were tentatively identified. These OPLS-DA models and biomarkers provided an objective approach to verify participant compliance in future clinical trials.

Modifications of the urinary metabolome in young women after cranberry juice consumption were revealed using the UHPLC-Q-orbitrap-HRMS-based metabolomics approach.

The objectives of this research were to investigate urinary metabolome modifications and discover potential intake biomarkers in young women after cranberry juice consumption. Fifteen female college students were given either cranberry juice or apple juice for three days using a cross-over design. Urine samples were collected before and after juice consumption. The metabolome in the urine was analyzed using UHPLC-Q-orbitrap-HRMS-based metabolomics followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). An S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that cranberry juice consumption significantly altered the urinary metabolome. Compared to the baseline urine or urine after apple juice consumption, cranberry juice consumption increased urinary excretion of both exogenous and endogenous metabolites. The tentatively identified exogenous metabolites included quinic acid, coumaric acid, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(dihydroxyphenyl)-γ-valerolactone sulfate, diphenol glucuronide, 3,4-dihydroxyphenyl propionic acid, 3-(hydroxyphenyl) propionic acid, 4-O-methylgallic acid, trihydroxybenzoic acid and 1,3,5-trimethoxybenzene. Modifications of endogenous metabolites after cranberry juice consumption included the increases in homocitric acid, hippuric acid, 3-hydroxy-3-carboxymethyl-adipic acid, (2)3-isopropylmalate, pimelic acid and N-acetyl-l-glutamate 5-semialdehyde. These metabolites may serve as urinary biomarkers of cranberry juice consumption and contribute to the bioactivities of cranberries against urinary tract infection.

Pectic Oligosaccharides from Cranberry Prevent Quiescence and Persistence in the Uropathogenic Escherichia coli CFT073.

Urinary tract infections (UTIs) caused by Escherichia coli create a large burden on healthcare and frequently lead to recurrent infections. Part of the success of E. coli as an uropathogenic bacterium can be attributed to its ability to form quiescent intracellular reservoirs in bladder cells and its persistence after antibiotic treatment. Cranberry juice and related products have been used for the prevention of UTIs with varying degrees of success. In this study, a group of cranberry pectic oligosaccharides (cPOS) were found to both inhibit quiescence and reduce the population of persister cells formed by the uropathogenic strain, CFT073. This is the first report detailing constituents of cranberry with the ability to modulate these important physiological aspects of uropathogenic E. coli. Further studies investigating cranberry should be keen to include oligosaccharides as part of the 'active' cocktail of chemical compounds.

Cranberry extracts promote growth of Bacteroidaceae and decrease abundance of Enterobacteriaceae in a human gut simulator model.

The opportunistic pathogen Escherichia coli, a common member of the human gut microbiota belonging to the Enterobacteriaceae family, is the causative agent of the majority of urinary tract infections (UTIs). The gut microbiota serves as a reservoir for uropathogenic E. coli where they are shed in feces, colonize the periurethral area, and infect the urinary tract. Currently, front line treatment for UTIs consists of oral antibiotics, but the rise of antibiotic resistance is leading to higher rates of recurrence, and antibiotics cause collateral damage to other members of the gut microbiota. It is commonly believed that incorporation of the American cranberry, Vaccinium macrocarpon, into the diet is useful for reducing recurrence of UTIs. We hypothesized such a benefit might be explained by a prebiotic or antimicrobial effect on the gut microbiota. As such, we tested cranberry extracts and whole cranberry powder on a human gut microbiome-derived community in a gut simulator and found that cranberry components broadly modulate the microbiota by reducing the abundance of Enterobacteriaceae and increasing the abundance of Bacteroidaceae. To identify the specific compounds responsible for this, we tested a panel of compounds isolated from cranberries for activity against E. coli, and found that salicylate exhibited antimicrobial activity against both laboratory E. coli and human UTI E. coli isolates. In a gut simulator, salicylate reduced levels of Enterobacteriaceae and elevated Bacteroidaceae in a dose dependent manner.

A randomized, double-blind, placebo-controlled pilot study to assess bacterial anti-adhesive activity in human urine following consumption of a cranberry supplement.

Urinary tract infections (UTIs) are one of the common bacterial infections treated with antibiotics. The North American cranberry is recommended for prophylaxis in women with recurrent UTIs as a nutritional alternative. The ability of cranberry components and their metabolites to inhibit adhesion of uropathogenic Escherichia coli (E. coli) is an important mechanism by which cranberry mitigates UTIs. The objective of this study was to evaluate urinary anti-adhesion activity against type 1 and P-type uropathogenic E. coli after consumption of cranberry +health™ cranberry supplement (cranberry chew). In this randomized, double-blind, placebo-controlled, crossover design pilot trial (n = 20), subjects consumed two cranberry or placebo chews, one in the morning and one in the evening. Clean-catch urine samples collected at the baseline and post-intervention (0-3, 3-6, 6-9, 9-12, 12-24, 24-30, 30-36 h) were tested for anti-adhesion effects with a mannose-resistant human red blood cell hemagglutination assay specific for P-type E. coli, or a T24 cell line model for type 1 E. coli. Urinary anti-adhesion activity against P-type E. coli after consumption of the cranberry chew was significantly greater (p < 0.05) than that observed with placebo chew at all time points except 24-36 h. Ex vivo anti-adhesion effects on type 1 E. coli were greater (p < 0.05) after cranberry chew consumption than placebo chew at 3-6 and 6-9 h urine collections. In conclusion, consumption of cranberry +health™ cranberry supplement exhibited greater ex vivo urinary anti-adhesion activity compared to placebo, suggesting that it may have the potential to help promote urinary tract health.

Some New Findings Regarding the Antiadhesive Activity of Cranberry Phenolic Compounds and Their Microbial-Derived Metabolites against Uropathogenic Bacteria.

Findings concerning the antiadhesive activity of cranberry phenolic compounds and their microbial-derived metabolites against Gram-negative ( Escherichia coli ATCC 53503 and DSM 10791) and Gram-positive ( Enterococcus faecalis 04-1) bacteria in T24 cells are reported. A-Type procyanidins (A2 and cinnamtannin B-1) exhibited antiadhesive activity (at concentrations ≥250 µM), a feature that was not observed for B-type procyanidins (B2). The metabolites hippuric acid and α-hydroxyhippuric acid also showed effective results at concentrations ≥250 µM. With regard to conjugated metabolites, sulfation seemed to increase the antiadhesive activity of cranberry-derived metabolites as 3-(3,4-dihydroxyphenyl)propionic acid 3- O-sulfate presented active results, unlike its corresponding nonsulfated form. In contrast, methylation decreased antiadhesive activity as 3,4-dihydroxyphenylacetic acid was found to be active but not its corresponding methylated form (4-hydroxy-3-methoxyphenylacetic acid). As a whole, this work sustains the antiadhesive activity of cranberry-derived metabolites as one of the mechanisms involved in the beneficial effects of cranberries against urinary tract infections.

Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial.

PURPOSE: We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. METHODS: 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m2) with abdominal adiposity (waist: hip > 0.8 for women and > 0.9 for men; waist: height ≥ 0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. RESULTS: Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P < 0.05). Interferon-γ was elevated (P < 0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P < 0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P < 0.05). CONCLUSIONS: An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Development of a Thiolysis HPLC Method for the Analysis of Procyanidins in Cranberry Products.

The objective of this study was to develop a thiolysis HPLC method to quantify total procyanidins, the ratio of A-type linkages, and A-type procyanidin equivalents in cranberry products. Cysteamine was utilized as a low-odor substitute of toluene-α-thiol for thiolysis depolymerization. A reaction temperature of 70 °C and reaction time of 20 min, in 0.3 M of HCl, were determined to be optimum depolymerization conditions. Thiolytic products of cranberry procyanidins were separated by RP-HPLC and identified using high-resolution mass spectrometry. Standards curves of good linearity were obtained on thiolyzed procyanidin dimer A2 and B2 external standards. The detection and quantification limits, recovery, and precision of this method were validated. The new method was applied to quantitate total procyanidins, average degree of polymerization, ratio of A-type linkages, and A-type procyanidin equivalents in cranberry products. Results showed that the method was suitable for quantitative and qualitative analysis of procyanidins in cranberry products.