Dataset Information

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

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.

Trial registration

Clinical trial registration number: ClinicalTrials.gov NCT01776021 .

SUBMITTER: Straub TJ

PROVIDER: S-EPMC7890861 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Straub Timothy J TJ Chou Wen-Chi WC Manson Abigail L AL Schreiber Henry L HL Walker Bruce J BJ Desjardins Christopher A CA Chapman Sinéad B SB Kaspar Kerrie L KL Kahsai Orsalem J OJ Traylor Elizabeth E Dodson Karen W KW Hullar Meredith A J MAJ Hultgren Scott J SJ Khoo Christina C Earl Ashlee M AM

BMC microbiology 20210218 1

<h4>Background</h4>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 ...[more]

PMID: 33596852

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Project description:Aim: Cranberries (Vaccinium macrocarpon) are traditionally used in prevention of urinary tract infections (UTIs). The authors' aim was to evaluate effects of a supplement containing cranberry extract, pumpkin seed extract, vitamin C, and vitamin B2 on recurrent uncomplicated UTIs in women and their intestinal microbiota. Methods: A prospective, uncontrolled exploratory study was conducted in women with recurrent uncomplicated UTIs. The primary exploratory outcome was the number of UTIs in a 6-month prospective observation period compared with a 6-month retrospective period. Further outcomes included number of antibiotics, quality of life (SF-36), intestinal microbiota (assessed by 16S rRNA amplicon sequencing), and evaluation questions. Parameters were assessed at baseline and after 1, 2, and 7 months (start of intake of cranberry supplement after 1 month for 6 months). p-Values were calculated with the pairwise Wilcoxon signed-rank test for α diversity and permutational multivariate analysis of variance. Results: Twenty-three women (aged 52.7 ± 12.4 years) were included in the study. Participants reported 2.2 ± 0.8 UTIs (at baseline) in the previous 6 months. After 6 months of cranberry intake, participants reported a significant decrease to 0.5 ± 0.9 UTIs (p < 0.001). Number of antibiotic therapies was also significantly (p < 0.001) reduced by 68% during 6 months of cranberry intake (0.14 ± 0.35) when compared with 6 months retrospectively (1.14 ± 0.71). The SF-36 physical component score increased from 44.9 ± 5.5 at baseline to 45.7 ± 4.6 at 7 months (p = 0.16). The SF-36 mental component score decreased slightly from the baseline value of 46.5 ± 6.5 to 46.2 ± 6.4 at 7 months (p = 0.74). No significant intragroup mean changes at genus, family, or species level for α and β diversity within the intestinal microbiota were found. In the evaluation questions, participants rated the cranberry extract positively and considered it beneficial. The supplement intake was safe. Conclusions: This study shows that women with recurrent uncomplicated UTIs benefit from cranberry intake. Future larger clinical studies with further investigation of the mechanisms of action are required to determine the effects of cranberries on participants with uncomplicated UTIs.

Project description:One in three women will experience a clinically significant urinary tract infection (UTI) by age twenty-four and almost half will have at least one in their lifetime. Recurrent UTIs (rUTIs) are defined as having greater than two infections in a 6-month period, or three infections over twelve months, with complete resolution for at least two weeks. These may be due to relapse from incomplete treatment (persistence) or re-infection (new source). It may be difficult to distinguish between the two, where the same organism is cultured. There are several risk factors for rUTIs including an impairment of the body's immune system and virulence factors. Reversible or treatable causes are sought and excluded in the patient's initial review. Patient's with rUTI are often complex and difficult to manage. The long-term management options in women are multimodal and should focus on prevention of relapse and recurrence. Behavioural factors include adequate hydration, care with sexual hygiene, reducing one's body mass index (BMI) and post-void residual (PVR) volume. There are several non-antimicrobial options for rUTIs which have become a multi-billion-dollar business. Unfortunately, there are numerous studies which fail to show any major benefit or having conflicting data. Vaccines are currently being explored as a prevention strategy, delivered through injection, intra-nasal sprays, or vaginal suppositories, which are made from combinations of heat killed uro-pathogenic strains. There are no widely available vaccines at present due to limited clinical success. It is well established that appropriate antibiotic therapy results in higher rates of symptom relief and bacterial eradication in women with uncomplicated cystitis. There are several options for antimicrobial use which have been shown to be highly effective in reducing the risk of rUTI in women. The pain and discomfort of the UTI must be balanced with the cost and risk of developing resistance when using antimicrobials. Continuous prophylaxis, pre- and post-coital voiding, and self-starting are the three commonly accepted options for prophylaxis. The choice between these will depend upon patient preference, cultures and previous pattern of infection. Intra-vesical instillation of hyaluronic acid and chondroitin sulphate have been used for glycosaminoglycan (GAG) layer replenishment for many indications, including interstitial cystitis, overactive bladder syndrome, radiation cystitis and prevention of rUTI. At present, intra-vesical therapies are reserved for only those with the most unresponsive rUTIs. The principles of treating rUTI are to break the cycle and to treat any reversible causes. With our ever-expanding research knowledge, there are now many useful products that may be used for the successful treatment of rUTI. A management plan including a combination of a non-antimicrobial and selective antimicrobial regime for a minimum of six months should be considered. It is a prudent clinician that clearly defines this management plan, with reassurance of a finite period of therapy.

Project description:ImportanceIncreased hydration is often recommended as a preventive measure for women with recurrent cystitis, but supportive data are sparse.ObjectiveTo assess the efficacy of increased daily water intake on the frequency of recurrent cystitis in premenopausal women.Design, setting, and participantsRandomized, open-label, controlled, 12-month trial at a clinical research center (years 2013-2016). Among 163 healthy women with recurrent cystitis (≥3 episodes in past year) drinking less than 1.5 L of fluid daily assessed for eligibility, 23 were excluded and 140 assigned to water or control group. Assessments of daily fluid intake, urinary hydration, and cystitis symptoms were performed at baseline, 6- and 12-month visits, and monthly telephone calls.InterventionsParticipants were randomly assigned to drink, in addition to their usual fluid intake, 1.5 L of water daily (water group) or no additional fluids (control group) for 12 months.Main outcomes and measuresPrimary outcome measure was frequency of recurrent cystitis over 12 months. Secondary outcomes were number of antimicrobial regimens used, mean time interval between cystitis episodes, and 24-hour urinary hydration measurements.ResultsThe mean (SD) age of the 140 participants was 35.7 (8.4) years, and the mean (SD) number of cystitis episodes in the previous year was 3.3 (0.6). During the 12-month study period, the mean (SD) number of cystitis episodes was 1.7 (95% CI, 1.5-1.8) in the water group compared with 3.2 (95% CI, 3.0-3.4) in the control group, with a difference in means of 1.5 (95% CI, 1.2-1.8; P < .001). Overall, there were 327 cystitis episodes, 111 in the water group and 216 in the control group. The mean number of antimicrobial regimens used to treat cystitis episodes was 1.9 (95% CI, 1.7-2.2) and 3.6 (95% CI, 3.3-4.0), respectively, with a difference in means of 1.7 (95% CI, 1.3-2.1; P < .001). The mean time interval between cystitis episodes was 142.8 (95% CI, 127.4-160.1) and 84.4 (95% CI, 75.4-94.5) days, respectively, with a difference in means of 58.4 (95% CI, 39.4-77.4; P < .001). Between baseline and 12 months, participants in the water group, compared with those in the control group, had increased mean (SD) urine volume (1.4 [0.04] vs 0.1 [0.04] L; P < .001) and voids (2.4 [0.2] vs -0.1 [0.2]; P < .001) and decreased urine osmolality (-402.8 [19.6] vs -24.0 [19.5] mOsm/kg; P < .001).Conclusions and relevanceIncreased water intake is an effective antimicrobial-sparing strategy to prevent recurrent cystitis in premenopausal women at high risk for recurrence who drink low volumes of fluid daily.Trial registrationClinicalTrials.gov identifier: NCT02444975.

Dataset Information

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

Results

Conclusion

Trial registration

Publications

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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