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Urinary Tract Health and Antibacterial Benefits

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Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: a systematic review and meta-analysis with trial sequential analysis.

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Authors
Xia JiaYue, Yang Chao, Xu DengFeng, Xia Hui, Yang LiGang, Sun GuiJu
Journal
PLoS ONE 2021. 16(9
Abstract

The efficacy of cranberry (Vaccinium spp.) as adjuvant therapy in preventing urinary tract infections (UTIs) remains controversial. This study aims to update and determine cranberry effects as adjuvant therapy on the recurrence rate of UTIs in susceptible groups. According to PRISMA guidelines, we conducted a literature search in Web of Science, PubMed, Embase, Scopus, and the Cochrane Library from their inception dates to June 2021. We included articles with data on the incidence of UTIs in susceptible populations using cranberry-containing products. We then conducted a trial sequential analysis to control the risk of type I and type II errors. This meta-analysis included 23 trials with 3979 participants. We found that cranberry-based products intake can significantly reduce the incidence of UTIs in susceptible populations (risk ratio (RR) = 0.70; 95% confidence interval(CI): 0.59 ~ 0.83; P < 0.01). We identified a relative risk reduction of 32%, 45% and 51% in women with recurrent UTIs (RR = 0.68; 95% CI: 0.56 ~ 0.81), children (RR = 0.55; 95% CI: 0.31 ~ 0.97) and patients using indwelling catheters (RR = 0.49; 95% CI: 0.33 ~ 0.73). Meanwhile, a relative risk reduction of 35% in people who use cranberry juice compared with those who use cranberry capsule or tablet was observed in the subgroup analysis (RR = 0.65; 95% CI: 0.54 ~ 0.77). The TSA result for the effects of cranberry intake and the decreased risk of UTIs in susceptible groups indicated that the effects were conclusive. In conclusion, our meta-analysis demonstrates that cranberry supplementation significantly reduced the risk of developing UTIs in susceptible populations. Cranberry can be considered as adjuvant therapy for preventing UTIs in susceptible populations. However, given the limitations of the included studies in this meta-analysis, the conclusion should be interpreted with caution.

Cranberry (Vaccinium macrocarpon) dietary supplementation and fecal microbiota of Wistar rats.

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Authors
Chettaoui R, Mayot G, De Almeida L, Di Martino P.
Journal
Aims Microbiology. 7(2):257-270, 2021.
Abstract

Cranberry (Vaccinium macrocarpon) dietary supplementation can help prevention of urinary tract infections through the supply of proanthocyanidin-type polyphenols (PAC). The main uropathogenic bacteria are members of the intestinal microbiota. A randomized cross-over experiment was done to investigate whether cranberry dietary supplementation affects concentrations of thermotolerant coliforms, Enterococcus spp. and Lactobacillus spp. in rat faeces. Thirteen rats, housed in individual cages, received successively two diets as pellets during 7 days each: a standard diet without polyphenols and the standard diet supplemented with cranberry powder containing 10.9 mg/100 g of PAC. There was a 7 days wash-out period in between with standard diet without polyphenols. Body weight and feed intake were recorded. Faeces were collected on the last day of treatment, and crushed to count the different bacterial populations using the most probable number method. Thermotolerant coliforms were grown in BGBLB tubes and on MacConkey agar. Enterococcus spp. were grown in Rothe and Litsky broths and on KF Streptococcus agar. Lactobacillus spp. were grown in Man Rogosa Sharpe broth. Body mass gains were not affected by cranberry supplementation. This is consistent with equal food intake, cranberry powder not providing significant energy supplement. Cranberry dietary supplementation was associated with changes in fecal concentrations of thermotolerant coliforms, and Enterococcus spp. in some rats, but did not induce significant changes in bacterial fecal concentrations in a global population of 13 rats. In conclusion, we did not observe any significant effect of dietary cranberry supplementation on the fecal microbiota of Wistars rats for a 7-day diet.

Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? A feasibility randomised trial.

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Authors
Gbinigie, O., Allen, J., Williams, N., Michael, M., Hay, A. D., Heneghan, C., Boylan, A. M., Butler, C. C.
Journal
BMJ Open 2021. 11(2).
Abstract

Objectives: To determine the feasibility of conducting a randomised trial of the effectiveness of cranberry extract in reducing antibiotic use by women with symptoms of acute, uncomplicated urinary tract infection (UTI).Design: Open-label feasibility randomised parallel group trial. Setting: Four general practices in Oxfordshire.Participants: Women aged 18 years and above presenting to general practice with symptoms of acute, uncomplicated UTI.Interventions: Women were randomly assigned using Research Electronic Data Capture in a 1:1:1 ratio to: (1) immediate antibiotics alone (n=15); (2) immediate antibiotics and immediate cranberry capsules for up to 7 days (n=15); or (3) immediate cranberry capsules and delayed antibiotics for self-initiation in case of non-improvement or worsening of symptoms (n=16).Primary and secondary outcome measures: The primary outcome measures were: rate of recruitment of participants; numbers lost to follow-up; proportion of electronic diaries completed by participants; and acceptability of the intervention and study procedures to participants and recruiters. Secondary outcomes included an exploration of differences in symptom burden and antibiotic use between groups. Results: Four general practitioner practices (100%) were opened and recruited participants between 1 July and 2 December 2019, with nine study participants recruited per month on average. 68.7% (46/67) of eligible participants were randomised (target 45) with a mean age of 48.4 years (SD 19.9, range 18-81). 89.1% (41/46) of diaries contained some participant entered data and 69.6% (32/46) were fully complete. Three participants (6.5%) were lost to follow-up and two (4.4%) withdrew. Of women randomly assigned to take antibiotics alone (controls), one-third of respondents reported consuming cranberry products (33.3%, 4/12). There were no serious adverse events.Conclusions: It appears feasible to conduct a randomised trial of the use of cranberry extract in the treatment of acute, uncomplicated UTI in general practice

Effects of cranberry beverages on oxidative stress and gut microbiota in subjects with Helicobacter pylori infection: a randomized, double-blind, placebo-controlled trial.

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Authors
Gao Tao, Hou MeiLing, Zhang Bo, Pan Xin, Liu ChengXia, Sun ChongXiu, Jia MengRu, Lin Song, Xiong Ke, Ma AiGuo
Journal
Food and Function 2021. 12(15):6878-6888
Abstract

Helicobacter pylori-induced oxidative stress plays an important role in gastric diseases. H. pylori disturbs gut microbiota. The objective is to investigate the effects of cranberry beverages on oxidative stress biomarkers and gut microbiota in H. pylori positive subjects. 171 H. pylori positive participants were randomly assigned to one of the three groups: high-dose (HCb; 480 mL cranberry beverage), low-dose (LCb; 240 mL cranberry beverage plus 240 mL placebo) and placebo (480 mL). Subjects consumed the beverages daily for 4 weeks. Fasting blood samples were analyzed for oxidative stress biomarkers. The intestinal microbiome was analyzed by 16S rRNA sequencing. Compared with the placebo, HCb resulted in a significantly higher increase of total antioxidant capacity (mean +or- SD: 1.39 +or- 1.69 IU mL-1vs. 0.34 +or- 1.73 IU mL-1; p < 0.001) and a higher decrease of the lipid peroxidation product malondialdehyde (-7.29 +or- 10.83 nmol mg-1vs. -0.84 +or- 15.66 nmol mg-1; p=0.025). A significant dose-dependent effect on the elevation of superoxide dismutase was observed (p < 0.001). Microbiome data showed that consuming HCb and LCb led to a significant reduction of Pseudomonas (p < 0.05). In conclusion, the current research showed that consuming cranberry beverages significantly improved the antioxidant status in H. pylori positive subjects, which may be related to the reshaping of gut microbiota.

 

Effects of vaccination against coccidiosis on gut microbiota and immunity in broiler fed bacitracin and berry pomace.

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Authors
Das, Q., Shay, J., Gauthier, M., Yin XianHua, Hasted, T. L., Ross, K., Julien, C., Yacini, H., Kennes, Y. M., Warriner, K., Marcone, M. F., Diarra, M. S.
Journal
Frontiers in Immunology 2021. 12(June).
Abstract

Feeding practices have been found to influence gut microbiota which play a major role in immunity of poultry. In the present study, changes in cecal microbiota and humoral responses resulting in the 55 ppm bacitracin (BACI), 1% each of cranberry (CP1) and wild blueberry (BP1) pomace alone or in combination (CP+BP) feeding in broiler Cobb 500 vaccinated or not against coccidiosis were investigated. In the non-vaccinated group, no significant treatment effects were observed on performance parameters. Vaccination significantly affected bird's performance parameters particularly during the growing phase from 10 to 20 days of age. In general, the prevalence of coccidiosis and necrotic enteritis (NE) was reduced by vaccination (P < 0.05). BACI-treated birds showed low intestinal lesion scores, and both CP1 and BP1 feed supplementations reduced Eimeria acervulina and Clostridium perfringens incidences similar to BACI. Vaccination induced change in serum enzymes, minerals, and lipid levels in 21-day old birds while, levels of triglyceride (TRIG) and non-esterified fatty acids (NEFA) were higher (P < 0.05) in CP1 treated non-vaccinated group than in the control. The levels of NEFA were lower in BACI- and CP1-fed birds than in the control in non-vaccinated day 28 old birds. The highest levels of all estimated three immunoglobulins (IgY, IgM, and IgA) were found in the vaccinated birds. Metagenomics analysis of the cecal bacterial community in 21-day old birds showed the presence of Firmicutes (90%), Proteobacteria (5%), Actinobacteria (2%), and Bacteroidetes (2%). In the vaccinated group, an effect of BACI was noted on Proteobacteria (P = 0.03). Vaccination and/or dietary treatments influenced the population of Lactobacillaceae, Enterobacteriaceae, Clostridiaceae, and Streptococcaceae which were among the most abundant families. Overall, this study revealed that besides their beneficial effects on performance, alike bacitracin, berry pomaces in poultry feed have profound impacts on the chicken cecal microbiota and blood metabolites that could be influenced by vaccination against coccidiosis.

 

Efficacy of an orally administered combination of Lactobacillus paracasei LC11, cranberry and D-mannose for the prevention of uncomplicated, recurrent urinary tract infections in women.

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Authors
Murina F, Vicariotto F, Lubrano C
Journal
Urologia (Treviso). 88(1):64-68, 2021
Abstract

BACKGROUND: Most women experience a urinary tract infection (UTI) at least once in their lifetime. The present study determined the efficacy and safety of a combination of Lactobacillus paracasei LC11, cranberry and D-mannose (Lactoflorene Cist R) in the prophylaxis of recurrent uncomplicated UTIs in premenopausal women.METHODS: This single-centre study enrolled premenopausal women aged 18-50 years with an acute UTI and a history of recurrent uncomplicated UTIs. Patients were first treated with fosfomycin (3 g once a day for 2 days) to eliminate any underlying infection, followed by treatment with Lactoflorene Cist R once a day for 10 days/month for 90 days (Group 1), Lactoflorene Cist R once daily for 90 days (Group 2) or no treatment (Group 3; control). The main study endpoint was the rate of UTI recurrence during the study period. Any adverse events with treatment were also recorded.RESULTS: A total of 55 women (mean age 39.3 years; range: 20-46) were enrolled in the study. A significantly higher proportion of patients in the control group experienced UTIs during the study period compared with the two treatment groups (52.9% vs 16.0% in Group 1 and 15.5% in group 2; p < 0.01). Similarly, a higher proportion of patients in Group 1 (65.8%) and Group 2 (68.7%) remained UTI-free during the study versus the control group. No adverse events were reported in the treated patients.CONCLUSION: Prophylactic treatment with Lactoflorene Cist R was effective and safe in the management of recurrent uncomplicated UTIs in premenopausal women.

Efficacy of daily intake of dried cranberry 500 mg in women with overactive bladder: a randomized, double-blind, placebo controlled study.

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Authors
Cho, A., Eidelberg, A., Butler, D. J., Danko, D., Afshinnekoo, E., Mason, C. E., Chughtai, B.
Journal
Journal of Urology 2021. 205(2):507-513.
Abstract

Purpose: We sought to determine the efficacy of dried cranberry on reducing symptoms of overactive bladder in women.Materials and Methods: Eligible women aged 18 or older with overactive bladder were randomized to either daily dried cranberry powder (500 mg) or placebo (500 mg) and followed for 24 weeks. Efficacy was measured by 3-day voiding diaries and Overactive Bladder Questionnaire Short Form, Patient Perception of Bladder Condition, Sexual Quality of Life-Female and Pelvic Floor Distress Inventory surveys. Statistical analyses were performed by BIOFORTIS using SASR software version 9.4.Results: Of the 98 women who were randomized 77 completed all the visits and 60 were included in the per protocol analysis. Compared to placebo using per protocol analysis the cranberry group showed a significant reduction of daily micturitions (-1.91, 95% CI -3.74--0.88, p=0.0406), urgency episodes (-2.81, 95% CI -4.82--0.80, p=0.0069), and Patient Perception of Bladder Condition scores (-0.66, 95% CI -1.23-0.08, p=0.0258) at 24 weeks of followup. Mean volume per micturition, nocturia and the remaining survey outcomes did not differ significantly between the groups (p >0.05).Conclusions: Daily intake of dried cranberry powder reduced daily micturition by 16.4%, urgency episodes by 57.3% and patient perception of bladder condition by 39.7%. However, an intent-to-treat analysis showed no statistically significant difference between the groups for these measurements (p >0.05). Future larger studies with longer followup periods are needed to further determine the long-term effect of cranberry on overactive bladder.

High dose versus low dose standardized cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women: a double-blind randomized controlled trial

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Authors
Babar A, Moore L, Leblanc V, Dudonne S, Desjardins Y, Lemieux S, Bochard V, Guyonnet D, Dodin S
Journal
BMC Urology. 21(1):44, 2021 Mar 23.
Abstract

PURPOSE: Our objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection.MATERIAL AND METHODS: We recruited 145 healthy, adult women with a history of recurrent urinary tract infection, defined as >= 2 in the past 6 months or >= 3 in the past 12 months in this randomized, controlled, double-blind clinical trial. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (2 x 18.5 mg daily, n = 72) or a control low dose (2 x 1 mg daily, n = 73) for a 24-week period. During follow-up, symptomatic women provided urine samples for detection of pyuria and/or bacteriuria and received an appropriate antibiotic prescription. The primary outcome for the trial was the mean number of new symptomatic urinary tract infections during a 24-week intervention period. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria.RESULTS: In response to the intervention, a non-significant 24% decrease in the number of symptomatic urinary tract infections was observed between groups (Incidence rate ratio 0.76, 95%CI 0.51-1.11). Post-hoc analyses indicated that among 97 women who experienced less than 5 infections in the year preceding enrolment, the high dose was associated with a significant decrease in the number of symptomatic urinary tract infections reported compared to the low dose (age-adjusted incidence rate ratio 0.57, 95%CI 0.33-0.99). No major side effects were reported.CONCLUSION: High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year.TRIAL

Impact of cranberry juice consumption on gut and vaginal microbiota in postmenopausal women

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Authors
A Al Othaim, D Marasini, F Carbonero
Journal
Food Frontiers, 2, 282– 293. https://doi.org/10.1002/fft2.76
Abstract

Cranberries have long been purported to provide protection against urinary tract infections.There is a line of evidence suggesting that causal pathogens might be seeded from the bacteria reservoirs in the intestinal and vaginal tracts.We tested the hypothesis whether cranberry intake would reshape bacteria taxa in the gut, as well as the vaginal ecosystem.A total of 25 postmenopausal women were enrolled into a randomized, double-blind, placebo-controlled study.Stool samples and vaginal swabs were collected at baseline and after 15 days of consumption of placebo or cranberry beverages, microbiota analyses were performed by Illumina Miseq sequencing following a double-index 16S rRNA gene amplicon.All baseline stool samples generally fell in the Bacteroides enterotype.Significant increases of Prevotella (P = 0.04), Clostridium XIVa members (P = 0.04), Eggerthella (P = 0.03), and Bifidobacterium (P = 0.02) were shown following the cranberry juice intervention; this indicates modulation of the gut microbiota by cranberry components.Baseline vaginal microbiotas fell in three distinct patterns—Lactobacillus dominant, diversified microbiome, and Streptococcus dysbiosis.Compared with the placebo, the cranberry intervention significantly reduced the abundance of pathogenic Streptococcus (P = 0.04) in the dysbiosis group and increased commensal bacteria Anaerococcus, Finegoldia, Actinomyces, and Corynebacterium in the diversified microbiome and dysbiosis groups. Overall, these data suggest that cranberry consumption may improve vaginal microbiota composition in individuals with dysbiosis.Gut-borne taxa stimulation by the combination of cranberry oligosaccharides and polyphenols present in the cranberry product potentially mediates these beneficial properties.

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

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Authors
Straub, T. J., Chou WenChi, Manson, A. L., Schreiber, H. L., IV, Walker, B. J., Desjardins, C. A., Chapman, S. B., Kaspar, K. L., Kahsai, O. J., Traylor Elizabeth, Dodson, K. W., Hullar, M. A. J., Hultgren, S. J., Khoo, C., Earl, A. M.
Journal
BMC Microbiology 2021. 21(53):
Abstract

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..