The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran R). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran R were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran TM Phytosome TM, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was found effective thus confirming the ex-vivo results.

OBJECTIVE: This article provides a comprehensive literature review on nonantibiotic agents used for the prevention of urinary tract infections (UTIs) in women >=45 years of age.DESIGN: A structured review was performed by conducting a literature search to identify relevant studies pertaining to the use of nonantibiotic agents to prevent UTIs in women who were perimenopausal through postmenopausal. Recommendations were made for or against the use of each nonantibiotic agent, unless data were unavailable. Levels of evidence were assigned to each recommendation made.SETTING AND PARTICIPANTS: Studies on the prevention of UTIs with women subjects >=45 years of age in the community, inpatient, and long-term care settings were considered for inclusion.MEASURE: The efficacy and safety of using ascorbic acid, cranberry products, d-mannose, estrogens, lactobacilli, and methenamine hippurate for prevention of UTIs was assessed.RESULTS: There is evidence to support use of estrogens (A-I) in postmenopausal women, and cranberry capsules (C-I) in women >=45 years of age for the prevention of UTIs. There was a lack of evidence to make recommendations for or against the use of ascorbic acid, cranberry juice, cranberry capsules with high proanthocyanidin (PAC) content, d-mannose, lactobacillus, and methenamine hippurate in this population.CONCLUSIONS/IMPLICATIONS: Current studies support that estrogens and cranberry capsules may have a role in preventing UTIs in women >=45 years of age. Further research is needed to elucidate the role of these nonantibiotic agents and how they may be used to decrease antibiotic use.

Cranberry ( Vaccinium macrocarpon) juice is traditionally used for the prevention of urinary tract infections. Human urine produced after cranberry juice consumption can prevent Escherichia coli adhesion, but the antiadhesive urinary metabolites responsible have not been conclusively identified. Adult female sows were therefore fed spray-dried cranberry powder (5 g/kg/day), and urine was collected via catheter. Urine fractions were tested for antiadhesion activity using a human red blood cell (A+) anti-hemagglutination assay with uropathogenic P-fimbriated E. coli. Components were isolated from fractions of interest using Sephadex LH-20 gel filtration chromatography followed by HPLC on normal and reversed-phase sorbents with evaporative light scattering detection. Active urine fractions were found to contain a complex series of oligosaccharides but not proanthocyanidins, and a single representative arabinoxyloglucan octasaccharide was isolated in sufficient quantity and purity for full structural characterization by chemical derivatization and NMR spectroscopic methods. Analogous cranberry material contained a similar complex series of arabinoxyloglucan oligosaccharides that exhibited antiadhesion properties in preliminary testing. These results indicate that oligosaccharides structurally related to those found in cranberry may contribute to the antiadhesion properties of urine after cranberry consumption.

In the present study, unfermented and fermented cranberry juice in combination with the Antibiotics vancomycin and tigecycline were tested for their antimicrobial activity. Cranberry juice was fermented with a recently isolated potentially probiotic Lactobacillus paracasei K5. The tested strains selected for this purpose were Enterococcus faecalis, E. faecium, Enterobacter cloacae and Staphylococcus aureus. The methods followed were the determination of zones inhibition, Minimum Inhibitory Concentration (MIC) and Fractional Inhibitory Concentration Index (FICI). Tigecycline together with fermented juice exhibited larger Zones of Inhibition (ZOI) in strains of E. faecium (65 +/- 4.8 mm) compared to the respective ZOI with tigecycline and unfermented juice (no zone). The same outcome was also obtained with E. cloacae. Vancomycin together with fermented juice exhibited larger ZOI in strains of E. faecium (28 +/- 2.2 mm) compared to the respective ZOI with vancomycin and unfermented juice (24 +/- 2.3 mm). The lowest MIC values were recorded when tigecycline was combined with fermented cranberry juice against S. aureus strains, followed by the same combination of juice and antibiotic against E. cloacae strains. FICI revealed synergistic effects between fermented juice and tigecycline against a strain of E. faecium (A2020) and a strain of E. faecalis (A1940). Such effects were also observed in the case of fermented juice in combination with vancomycin against a strain of S. aureus (S18), as well as between fermented juice and tigecycline against E. cloacae (E1005 and E1007) strains. The results indicate that the antibacterial activity of juice fermented with the potentially probiotic L. paracasei K5 may be due to synergistic effects between some end fermentation products and the antibiotic agents examined.

Patients with chronic kidney disease (CKD) present many complications that potentially could be linked to increased cardiovascular mortality such as inflammation, oxidative stress, cellular senescence and gut dysbiosis. There is growing evidence suggesting that nutritional strategies may reduce some of these complications. Clinical studies suggest that supplementation of cranberries may have beneficial effects on human health such as prevention of urinary tract infections. More recently, the anti-inflammatory and anti-oxidant effects as well as modulation of gut microbiota provided by cranberry phytochemicals have drawn more attention. A better understanding of possible effects and mechanisms of action of cranberry supplementation in humans could inform researchers about warranted future directions for clinical studies targeting these complications in CKD patients by applying nutritional strategies involving cranberry supplementation.

Cranberry has been widely utilized as a popular botanical dietary supplement to prevent urinary tract infection. The study aims to evaluate the enhanced bactericidal activities of cranberry against uropathogenic Escherichia coli (UPEC) by adding a small quantity of naturally derived antimicrobials. The antibacterial effect was examined with cranberry extract alone (15 and 20%), three kinds of medium-chain fatty acids alone (caprylic, capric, and lauric acid; 0.05–1.0 mM), essential oils alone (carvacrol and thymol; 0.5–1.0 mM), and cranberry extract containing medium-chain fatty acids or essential oils at 37 °C for 1 min. The survivors were remarkably reduced with cranberry extract containing any of the antimicrobials. For example, cranberry extract (15 and 20%) with 1.0 mM of each caprylic acid, lauric acid, and carvacrol resulted in the complete eradication of UPEC (7.55 log reduction). Flow cytometry analysis of UPEC cells exposed to combined treatment showed clear membrane disruption and cell death (>95% of damage). Adding antimicrobials to cranberry extract did not affect (P > 0.05) the characteristics of the cranberry extract (Color, °Brix, pH). The present method may be more acceptable to consumers, who tend to avoid products containing synthetic chemicals and prefer the use of natural agents.

OBJECTIVE: To investigate the effect of cranberry extracts on saliva-derived polymicrobial biofilms with regards to biofilm biomass, acidogenicity, exopolysaccharide (EPS)/microbial biovolumes, colony forming unit (CFU) counts, and the relative abundance of specific caries- and health-associated bacteria.METHODS: Saliva-derived polymicrobial biofilms were grown for 96 h in a cariogenic environment and treated for 2 min every 12 h over the entire biofilm growth period with 500 mug/mL cranberry extract or vehicle control. The effect of the cranberry extract on biofilm behaviour was evaluated using different assays and its influence on key cariogenic and health-associated bacterial populations was assessed with a microarray real-time quantitative PCR method.RESULTS: Cranberry-treated biofilms showed significant drops in biomass (38% reduction, P < 0.001), acidogenicity (44% reduction, P < 0.001), EPS/microbial biovolume ratios (P = 0.033), and CFU counts (51% reduction, P = 0.001). Furthermore, the cranberry extracts effected a significantly lower relative abundance of caries-associated Streptococcus sobrinus (fold change 0.004, P = 0.002) and Provotella denticola (0.002, P < 0.001), and a significantly higher relative abundance of the health-associated Streptococcus sanguinis (fold change 90.715, P = 0.001).CONCLUSIONS: The cranberry extract lowered biofilm biomass, acidogenicity, EPS/microbial biovolumes, CFU counts, and modulated a beneficial microbial ecological change in saliva-derived polymicrobial biofilms.

Phenolic compounds in fruits such as cranberries have been shown to promote a number of biological activities. The purpose of this study was to investigate the effects of polyphenolic compound-containing lingonberry extract on oral streptococci and compare them with the known anti-cariogenic activity of cranberries. Water-soluble and polyphenol-rich fractions (Fractions I and II, respectively) were isolated from cranberries and lingonberries. The effects of those fractions on the biofilm formation ability and bioactivity of Streptococcus mutans MT8148R, Streptococcus sobrinus 6715, and Streptococcus sanguinis ATCC 10556 were then evaluated. Cranberry or lingonberry Fraction II (at 0.5-1 mg/ml) significantly reduced biofilm formation by S. mutans, S. sobrinus, and S. sanguinis. In contrast, cranberry or lingonberry Fraction I (at 0.5-2 mg/ml) increased biofilm formation by S. mutans and S. sobrinus, but not by S. sanguinis. Fractions I and II (at 1-2 mg/ml) also reduced the bioactivity of S. mutans, while Fraction II (at 0.5 mg/ml) enhanced the bioactivity of all tested strains. The results revealed that lingonberries contained a larger amount of polyphenol than cranberries and that they showed almost the same level of activity against the biofilm formation ability and bioactivity of oral streptococci. This indicates that polyphenol-rich lingonberry fraction offers a promising natural food derivative for prevention of dental caries.

Purpose: The purpose of this study was to investigate the effects of polyphenol-rich cranberry extracts on dual-species Streptococcus mutans-Candida. albicans biofilms implicated in contributing to the severity of early childhood caries. Methods: S. mutans-C. albicans biofilms were grown on saliva-coated hydroxyapatite discs (s-HA) mounted on the high-throughput Amsterdam Active Attachment model. The s-HA discs were treated with the cranberry extracts/vehicle control for five minutes just before biofilm growth and subsequently, for similar exposure times, after 12 hours and 24 hours of biofilm growth. The treated 24-hour-old biofilms were then assessed for acidogenicity, metabolic activity, exopolysaccharide (EPS)/microbial biovolumes, structural organization, and colony forming unit (CFU) counts. Results: Treatment with 500 to 1,000 mug/mL of the cranberry extracts produced significant reductions in acidogenicity and metabolic activity (P<0.0001) compared to the control-treated biofilms. A significant decrease in biovolumes of the EPS (P=0.003) and microbial biofilm components (P=0.007) was also seen. Qualitative assessment of confocal biofilm images revealed that the cranberry extract disrupted biofilm structural architecture. Finally, significantly fewer S. mutans (P=0.006) and C. albicans (P=0.036) CFUs were recovered from the cranberry-treated biofilms than from the control-treated bio-films. Conclusions: Cranberry extracts inhibited cariogenic virulence properties of S. mutans-C. albicans dual-species biofilms in an in vitro model.

Antibiotic resistance is spreading at an alarming rate among pathogenic bacteria in both medicine and agriculture. Interfering with the intrinsic resistance mechanisms displayed by pathogenic bacteria has the potential to make antibiotics more effective and decrease the spread of acquired antibiotic resistance. Here, it is demonstrated that cranberry proanthocyanidin (cPAC) prevents the evolution of resistance to tetracycline in Escherichia coli and Pseudomonas aeruginosa, rescues antibiotic efficacy against antibiotic-exposed cells, and represses biofilm formation. It is shown that cPAC has a potentiating effect, both in vitro and in vivo, on a broad range of antibiotic classes against pathogenic E. coli, Proteus mirabilis, and P. aeruginosa. Evidence that cPAC acts by repressing two antibiotic resistance mechanisms, selective membrane permeability and multidrug efflux pumps, is presented. Failure of cPAC to potentiate antibiotics against efflux pump-defective mutants demonstrates that efflux interference is essential for potentiation. The use of cPAC to potentiate antibiotics and mitigate the development of resistance could improve treatment outcomes and help combat the growing threat of antibiotic resistance