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.

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.

A daily consumption of cranberry juice (CJ) is linked to many beneficial health effects due to its richness in polyphenols but could also awake some intestinal discomforts due to its organic acid content and possibly lead to intestinal inflammation. Additionally, the impact of such a juice on the gut microbiota is still unknown. Thus, this study aimed to determine the impacts of a daily consumption of CJ and its successive deacidification on the intestinal inflammation and on the gut microbiota in mice. Four deacidified CJs (DCJs) (deacidification rates of 0, 40, 60, and 80%) were produced by electrodialysis with bipolar membrane (EDBM) and administered to C57BL/6J mice for four weeks, while the diet (CHOW) and the water were ad libitum. Different parameters were measured to determine intestinal inflammation when the gut microbiota was profiled. Treatment with a 0% DCJ did not induce intestinal inflammation but increased the gut microbiota diversity and induced a modulation of its functions in comparison with control (water). The effect of the removal of the organic acid content of CJ on the decrease of intestinal inflammation could not be observed. However, deacidification by EDBM of CJ induced an additional increase, in comparison with a 0% DCJ, in the Lachnospiraceae family which have beneficial effects and functions associated with protection of the intestine: the lower the organic acid content, the more bacteria of the Lachnospiraceae family and functions having a positive impact on the gut microbiota.

Helicobacter pylori infection is one of the most common chronic bacterial infections. Cranberry has been suggested for H. pylori eradication. We aimed to conduct the first meta-analysis to summarise current evidence on effects of cranberry supplementation on H. pylori eradication in H. pylori positive subjects. We searched the online databases up to December 2020. Four randomised clinical trials (RCT) were included with human subjects, investigating the effect of cranberry on H. pylori eradication. The pooled results were expressed as the OR with 95 % CI. Based on five effect sizes with a total sample size of 1935 individuals, we found that according to the OR, there was a positive effect of cranberry supplementation on H. pylori eradication, increasing the chance of H. pylori eradication by 1.27 times, but this relationship was not statistically significant (overall OR: 1.27; 95 % CI 0.63, 2.58). The results also indicated the moderate between-study heterogeneity (I2 = 63.40 %; P = 0.03) of the studies. However, there were no significant differences in some subgroup analyses in the duration of treatment, the duration of follow-up and the Jadad score. Our findings revealed that although cranberry had a positive effect on H. pylori eradication in adults, this effect was not statistically significant. Due to the small number of included studies and moderate heterogeneities, the potential of cranberry supplementation on H. pylori eradication should be validated in large, multicentre and well-designed RCT in the future.

The Developmental Origins of Health and Disease (DOHaD) concept has been proposed to explain the influence of environmental conditions during critical developmental stages on the risk of diseases in adulthood. The aim of this study was to compare the impact of the prenatal vs. postnatal environment on the gut microbiota in dams during the preconception, gestation and lactation periods and their consequences on metabolic outcomes in offspring. Here we used the cross-fostering technique, e.g. the exchange of pups following birth to a foster dam, to decipher the metabolic effects of the intrauterine versus postnatal environmental exposures to a polyphenol-rich cranberry extract (CE). CE administration to high-fat high-sucrose (HFHS)-fed dams improved glucose homeostasis and reduced liver steatosis in association with a shift in the maternal gut microbiota composition. Unexpectedly, we observed that the postnatal environment contributed to metabolic outcomes in female offspring, as revealed by adverse effects on adiposity and glucose metabolism, while no effect was observed in male offspring. In addition to the strong sexual dimorphism, we found a significant influence of the nursing mother on the community structure of the gut microbiota based on alpha-diversity and beta-diversity indices in offspring. Gut microbiota transplantation (GMT) experiments partly reproduced the observed phenotype in female offspring. Our data support the concept that the postnatal environment represents a critical window to influence future sex-dependent metabolic outcomes in offspring that are causally but partly linked with gut microbiome alterations.

Urinary tract infections (UTIs) are among the most common causes of infections in women. Via the fecal-perineal-urethral route, uropathogenic Escherichia coli (UPEC) can cause ascending urinary tract infections, including cystitis and pyelonephritis. These infections re-occur within six months or they account for, at least, three episodes within a year of recurrent UTIs (rUTIs). Long term and continuous antibiotic treatment or prophylaxis should be considered as the last options in rUTIs. Conversely, updated European Association of Urology guidelines recommend non-antimicrobial approaches to prevent rUTIs. Accordingly, several studies reported the efficacy of number of natural molecules in inhibiting UPEC adhesion to bladder cells, restraining bacterial growth, as well as stimulating the host innate immune defenses, and protecting the bladder and the kidney mucosa. Therefore, we propose an "anti-UPEC" diet enriched of foods containing natural compounds that were proven effective against UPEC, such as D-mannose, cranberry extracts and medicinal plants. Being a valuable and safe clinical approach to reduce UTI recurrence and limiting the detrimental effects of long and continuous antibiotic prophylaxis, dietary interventions should be evaluated in future clinical trials.

This study aimed to investigate whether cranberry extract could reduce lower urinary tract (LUT) and gastro-intestinal (GI) signs in feline idiopathic cystitis (FIC). Twenty-one client-owned cats were randomly allocated to two groups: a treated group (T, n = 10) receiving daily an oral nutritional supplement containing cranberry extract and a control group (C, n = 11). Owners were trained to recognise daily LUT and GI signs. Physical examination, urinalysis and bladder ultrasonography were performed at day 0 (T0), 15 (T15), 30 (T30), 60 (T60). Both groups showed an improvement for dysuria and periuria from T0 to T30 (p < 0.05), but only in cats of the T group, LUT signs disappeared at T60. A significant improvement in the T group was also observed for GI signs and bladder ultrasonography at T60 (p = 0.03). Urinalysis did not show any significant differences. This preliminary study suggests that cranberry could be effective in reducing LUT and GI signs in FIC

Adhesion of P-type and type-1 fimbriated uropathogenic E. coli (UPEC) to uroepithelial cells initiates urinary tract infections (UTIs). This research aimed to evaluate the capacities of selected cranberry polyphenols and their microbial metabolites to inhibit such adhesion in vitro using a modified fluorometric method. Data showed that the inhibition capacity of myricetin increased with concentration and plateaued at 70%. It had IC50 values of 13.2 M against P-type E. coli and 5.50 M against type-1 E. coli. Quercetin showed similar anti-adhesion capacities to myricetin. Procyanidin A2 and B2 had weaker anti-adhesion activities than myricetin and quercetin, with maximal inhibition capacities of 20%-30% against UPEC. Hippuric acid, a major metabolite of cranberry polyphenols in human urine, showed a maximal inhibition of 20% at 558 M against type-1 E. coli adhesion, whereas no anti-adhesion activity against P-type E. coli was detected. The fractions of cranberry fruit powder enriched with proanthocyanidin polymers showed the highest anti-adhesion activities compared to the fractions enriched with anthocyanins, flavonols, or proanthocyanidin oligomers. Overall, the anti-adhesion activities of cranberry polyphenols and metabolites depend on their structures and the types of fimbriae on E. coli.