Cranberries (Vaccinium macrocarpon) represent an important source of anthocyanins, flavan-3-ols and flavonols. This study aimed at investigating in vitro the human microbial metabolism of (poly)phenols, principally flavan-3-ols, of unformulated- and phytosome-formulated cranberry extracts. After powder characterization, a 24-h fermentation with human faecal slurries was performed, standardizing the concentration of incubated proanthocyanidins. Cranberry (poly)phenol metabolites were quantified by uHPLC-MS2 analyses. The native compounds of both unformulated- and phytosome-formulated cranberry extracts were metabolized under faecal microbiota activity, resulting in twenty-four microbial metabolites. Although some differences appeared when considering different classes of colonic metabolites, no significant differences in the total amount of metabolites were established after 24 h of incubation period. These results suggested that a different formulation had no effect on flavan-3-ol colonic metabolism of cranberry and both unformulated- and phytosome-formulated extract. Both formulations displayed the capability to be a potential source of compounds which could lead to a wide array of gut microbiota metabolites in vitro.

Ischemia with no obstructive coronary artery disease (INOCA) is a common diagnosis with a higher prevalence in women compared to men. Despite the absence of obstructive coronary artery disease and no structural heart disease, INOCA is associated with major adverse cardiovascular outcomes as well a significant contributor to angina and related disability. A major feature of INOCA is coronary microvascular dysfunction (CMD), which can be detected by non-invasive imaging and invasive coronary physiology assessments in humans. CMD is associated with epicardial endothelial-dependent and -independent dysfunction, diffuse atherosclerosis, and left-ventricular hypertrophy, all of which lead to insufficient blood flow to the myocardium. Inflammatory and oxidative stress signaling, upregulation of the renin-angiotensin-aldosterone system and adrenergic receptor signaling are major drivers of CMD. Treatment of CMD centers around addressing cardiovascular risk factors; however, there are limited treatment options for those who do not respond to traditional anti-anginal therapies. In this review, we highlight the ability of berry-derived polyphenols to modulate those pathways. The evidence supports the need for future clinical trials to investigate the effectiveness of berries and their polyphenols in the treatment of CMD in INOCA patients.

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..

Purpose: Extensive inter-individual variability exists in the production of flavan-3-ol metabolites. Preliminary metabolic phenotypes (metabotypes) have been defined, but there is no consensus on the existence of metabotypes associated with the catabolism of catechins and proanthocyanidins. This study aims at elucidating the presence of different metabotypes in the urinary excretion of main flavan-3-ol colonic metabolites after consumption of cranberry products and at assessing the impact of the statistical technique used for metabotyping. Methods: Data on urinary concentrations of phenyl-P-valerolactones and 3-(hydroxyphenyl)propanoic acid derivatives from two human interventions has been used. Different multivariate statistics, principal component analysis (PCA), cluster analysis, and partial least square-discriminant analysis (PLS-DA), have been considered. Results: Data pre-treatment plays a major role on resulting PCA models. Cluster analysis based on k-means and a final consensus algorithm lead to quantitative-based models, while the expectation-maximization algorithm and clustering according to principal component scores yield metabotypes characterized by quali-quantitative differences in the excretion of colonic metabolites. PLS-DA, together with univariate analyses, has served to validate the urinary metabotypes in the production of flavan-3-ol metabolites and to confirm the robustness of the methodological approach.Conclusions: This work proposes a methodological workflow for metabotype definition and highlights the importance of data pre-treatment and clustering methods on the final outcomes for a given dataset. It represents an additional step toward the understanding of the inter-individual variability in flavan-3-ol metabolism.

A considerable proportion of children experience a recurrence of urinary tract infection (UTI) following the first episode. While low-dose antibiotic prophylaxis has been the mainstay for the prevention of UTI, recent evidence raised concerns over their efficacy and safety. Hence, we aim to systematically synthesize evidence on the efficacy and safety of non-antibiotic prophylactic interventions for UTI. Using keywords related to study population (children) and intervention (non-antibiotic), we searched CENTRAL, Embase, PubMed, and Web of Science for randomized controlled trials (RCTs) published until August 2020. RCTs comparing any non-antibiotic interventions with placebo/antibiotics for prevention of UTIs in children were considered eligible. We used a random-effect model to provide pooled estimates. Sixteen trials evaluating 1426 participants were included. Cranberry was as effective as antibiotic prophylaxis (RR: 0.92; 95% CI: 0.56-1.50) but better than placebo/no therapy (RR: 0.48; 95% CI: 0.28-0.80) in reducing UTI recurrence. Probiotic therapy was more effective in reducing UTI recurrence (RR: 0.52; 95% CI: 0.29-0.94) when compared with placebo. While probiotic therapy was not better than antibiotics prophylaxis in preventing UTI (RR: 0.82; 95% CI: 0.56-1.21), they have a lower risk of antibiotic resistance (RR: 0.38; 95% CI: 0.21-0.69). Conclusion: Cranberry products and probiotics are the two non-antibiotic interventions that have been chiefly evaluated, reduce the risk of UTI recurrence when compared with placebo in children with a normal urinary tract. The findings from this systematic review suggest that while cranberry and probiotics may be used, there is a definite need to identify better and more acceptable non-antibiotic interventions.

The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200-400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects..

Lead (Pb) has been identified as a hazardous heavy metal and a pollutant in the environment, especially due to its human activity. It poisons several physiological systems, such as the hepatic, renal, reproductive, as well as nervous systems, because of an elevation in oxidative damage caused by the formation of reactive oxygen species (ROS). Cranberry is a powerful antioxidant in addition to being a component of an anti-inflammatory disease treatments. The goal of this study was to see if cranberry extract could protect rats from toxicity caused by lead acetate. Addition of cranberry extract at a dose of 75 and 150 mg/kg to rats allowed to treat with lead acetate at a dose of 50 mg/kg to 6 weeks significantly protected the rats from the lead acetate-induced increase in both serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenases (LDH), total and direct bilirubin, alkaline phosphatase (ALP), creatinine, urea, total cholesterol (TC), triglycerides (TG), LDL-C and VLDL-C in addition against an elevation of serum glucose, tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA).Treatment with cranberry extract at a dose of 75 and 150 mg/kg also led to a valuable rise in serum total soluble protein, albumin, globulin, HDL-C, triiodothyronine (T3), total thyroxine (T4) as well as hepatic and renal tissue of reduced glutathione (GSH), superoxide dismutase (SOD), catalase activity (CAT) and total antioxidant capacity (TAC) as compared to lead acetate-treated rats. Cranberry has hepato-renal protective impacts in restoring liver and kidney function, according to histopathological evaluation of hepatic and renal tissues. These findings have shown, in conclusion, that cranberry extract has such a strong protective effect in rats suffering from hepato-renal toxicity caused by lead acetate.

Cranberry consumption has numerous health benefits, with experimental reports showing its anti-inflammatory and anti-tumor properties. Importantly, microbiome research has demonstrated that the gastrointestinal bacterial community modulates host immunity, raising the question of whether the cranberry-derived effect may be related to its ability to modulate the microbiome. Only a few studies have investigated the effect of cranberry products on the microbiome to date. Especially because cranberries are rich in dietary fibers, the extent of microbiome modulation by polyphenols, particularly proanthocyanidins (PACs), remains to be shown. Since previous work has only focused on long-term effects of cranberry extracts, in this study we investigated the effect of a water-soluble, PAC-rich cranberry juice extract (CJE) on the short-term dynamics of a human-derived bacterial community in a gnotobiotic mouse model. CJE characterization revealed a high enrichment in PACs (57%), the highest ever utilized in a microbiome study. In a 37-day experiment with a ten-day CJE intervention and 14-day recovery phase, we profiled the microbiota via 16S rRNA sequencing and applied diverse time-series analytics methods to identify individual bacterial responses. We show that daily administration of CJE induces distinct dynamic patterns in bacterial abundances during and after treatment, before recovering resiliently to pre-treatment levels. Specifically, we observed an increase of Akkermansia muciniphila and Clostridium hiranonis at the expense of Bacteroides ovatus after the offset of the selection pressure imposed by the PAC-rich CJE. This demonstrates that termination of an intervention with a cranberry product can induce changes of a magnitude as high as the intervention itself.

This open pilot registry study aimed to evaluate and compare the prophylactic effects of PycnogenolR or cranberry extract in subjects with previous, recurrent urinary tract infections (UTI) or interstitial cystitis (IC). Methods: Inclusion criteria were recurrent UTI or IC. One subject group was supplemented with 150 mg/day PycnogenolR, another with 400 mg/day cranberry extract, and a group served as a control in a 2-month open follow-up. Results: 64 subjects with recurrent UTI/IC completed the study. The 3 groups of subjects were comparable at baseline. All subjects had significant symptoms (minor pain, stranguria, repeated need for urination, and lower, anterior abdominal pain) at inclusion. In the course of the study, the subjects reported no tolerability problems or side effects. The incidence of UTI symptoms, in comparison with the period before inclusion in the standard management (SM) group, decreased significantly; there was a more pronounced decrease in the rate of recurrent infections in the PycnogenolR group (p < 0.05). The improvement in patients supplemented with PycnogenolR was significantly superior to the effects of cranberry. At the end of the study, all subjects in the PycnogenolR group were infection-free (p < 0.05vs. cranberry). Significantly, more subjects were completely symptom-free after 2 months of management with PycnogenolR (20/22) than with SM (18/22) and cranberry (16/20). Conclusions: This pilot registry suggests that 60 days of PycnogenolR supplementation possibly decrease the occurrence of UTIs and IC without side effects and with an efficacy superior to cranberry.

Functional plant-based foods (such as fruits, vegetables, and berries) can improve health, have a preventive effect, and diminish the risk of different chronic diseases during in vivo and in vitro studies. Berries contain many phytochemicals, fibers, vitamins, and minerals. The primary phytochemicals in berry fruits are phenolic compounds including flavonoids (anthocyanins, flavonols, flavones, flavanols, flavanones, and isoflavonoids), tannins, and phenolic acids. Since berries have a high concentration of polyphenols, it is possible to use them for treating various diseases pharmacologically by acting on oxidative stress and inflammation, which are often the leading causes of diabetes, neurological, cardiovascular diseases, and cancer. This review examines commonly consumed berries: blackberries, blackcurrants, blueberries, cranberries, raspberries, black raspberries, and strawberries and their polyphenols as potential medicinal foods (due to the presence of pharmacologically active compounds) in the treatment of diabetes, cardiovascular problems, and other diseases. Moreover, much attention is paid to the bioavailability of active berry components. Hence, this comprehensive review shows that berries and their bioactive compounds possess medicinal properties and have therapeutic potential. Nevertheless, future clinical trials are required to study and improve the bioavailability of berries' phenolic compounds and extend the evidence that the active compounds of berries can be used as medicinal foods against various diseases.