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.

The microbiome plays a major role in polyphenol metabolism, producing metabolites that are bioavailable and potentially more bioactive than the compounds from which they are derived. However, the microbiome can vary among individuals, and especially for those with co-morbidities, such as ulcerative colitis. In subjects with ulcerative colitis, the consequence of a 'dysbiotic' microbiome is characterized by decreased diversity of microbiota that may impact their capability to metabolize polyphenols into bioavailable metabolites. On this premise, the microbiome metabolism of cranberry polyphenols between healthy individuals and those with ulcerative colitis was compared in vitro. Fecal samples from volunteers, with or without diagnosed ulcerative colitis, were cultured anaerobically in the presence of cranberry polyphenols. The resulting metabolites were then quantified via LC-ESI-MS/MS. 16S rRNA metagenomics analysis was also utilized to assess differences in microbiota composition between healthy and ulcerative colitis microbiomes and the modulatory effects of cranberry polyphenols on microbiota composition. Healthy microbiomes produced higher (p < 0.05) concentrations of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone and 3-hydroxyphenylacetic acid in comparison to ulcerative colitis microbiomes. Additionally, healthy microbiomes contained a higher (p < 0.05) abundance of Ruminococcaceae, which could explain their ability to produce higher concentrations of cranberry polyphenol metabolites. Health status and the presence of cranberry polyphenols also significantly impacted the production of several short-chain and branched-chain fatty acids. These results suggest that efficiency of polyphenol metabolism is dependent on microbiota composition and future works should include metabolite data to account for inter-individual differences in polyphenol metabolism.

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.

The American cranberry, Vaccinium macrocarpon, contains fibers and (poly)phenols that could exert health-promoting effects through modulation of gut microbiota. This study aimed to investigate how a freeze-dried whole cranberry powder (FCP) modulated metabolite production and microbial composition using both a 48-h incubation strategy and a long-term human gut simulator study with the M-SHIME (Mucosal Simulator of the Human Intestinal Microbial Ecosystem). FCP was repeatedly administered over three weeks. The studies included five and three study subjects, respectively. In both models, FCP significantly increased levels of health-related short-chain fatty acids (SCFA: acetate, propionate and butyrate), while decreased levels of branched-chain fatty acids (markers of proteolytic fermentation). Interestingly, FCP consistently increased luminal Bacteroidetes abundances in the proximal colon of the M-SHIME (+17.5 ± 9.3%) at the expense of Proteobacteria (−10.2 ± 1.5%). At family level, this was due to the stimulation of Bacteroidaceae and Prevotellaceae and a decrease of Pseudomonodaceae and Enterobacteriaceae. Despite of interpersonal differences, FCP also increased the abundance of families of known butyrate producers. Overall, FCP displayed an interesting prebiotic potential in vitro given its selective utilization by host microorganisms and potential health-related effects on inhibition of pathogens and selective stimulation of beneficial metabolites.

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.

The secondary metabolite content of cranberry fruits can vary with cultivar and environmental factors, which may in turn impact their potential biological activities. To evaluate the influence of composition on anti-inflammatory activity, cranberry fruits were collected from two major U.S. growing regions. Eight extracts from these fruits were prepared, analyzed for phytochemical composition, and evaluated for their anti-inflammatory effects in human monocytes (THP-1 cells). The extracts varied widely in polyphenol and triterpenoid content. All were able to reduce lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokine interleukin 6 (IL-6) at 100 μg/mL, with inhibition ranging between 18.8 and 48.8%. Of these, three extracts high in anthocyanins, triterpenoids, or total polyphenols decreased levels of IL-6 and tumor necrosis factor alpha (TNF-α) at concentrations of 0.1–10 μg/mL compared to LPS-exposed control. Several individual cranberry phytochemicals were also capable of reducing production of IL-6, IL-1β, and TNF-α. The data suggest that phytochemicals present in varying quantities in cranberry fruits including anthocyanins, hyperoside, ursolic acid, and corosolic acid play a role in the anti-inflammatory effects of cranberry extracts on human monocytes.

Fruit and fruit juices are a valuable source of bioactive compounds, which can protect our organisms from oxidative stress. The phenolic compounds and other phytochemicals may affect the antimicrobial properties of juices. The aim of this study has been to evaluate antioxidant and antimicrobial properties of selected berry juices and vitamin C-rich fruit juices. The research material was composed of seven juices, including three from berries (elderberry chokeberry, cranberry), three from vitamin C-rich fruit (sea buckthorn, wild rose, Japanese quince) and one exotic juice from noni fruit. Antioxidant capacity, total polyphenol, total flavonoid and total anthocyanin content were determined. Furthermore, the antimicrobial activity and the minimal inhibitory concentration (MIC) as well as the minimal bactericidal concentration (MBC) were evaluated. The research showed that fruit juices from wild rose, chokeberry and Japanese quince had the highest antioxidant capacity. These juices were characterised by the rich content of polyphenols. Elderberry and chokeberry juices had the highest total anthocyanins. The juices differed in the content of bioactive compounds and specific bactericidal properties against Gram-positive or Gram-negative bacteria. Fruit juices from cranberry, Japanese quince and sea buckthorn had the highest antimicrobial activity. Wild rose, chokeberry and elderberry juices, despite their high antioxidant properties, showed antimicrobial activity only against Gram-positive strains, except Enterococcus faecalis and Clostridium perfringens. Significant differences in the content of bioactive compounds in fruit juices affect the antimicrobial properties juices.

The involvement of hypoxia-inducible factor-1 alpha (HIF-1 alpha), transforming growth factor-beta 1 (TGF-beta 1), Smad and beta-catenin signaling pathway in non-alcoholic fatty liver disease (NAFLD) is not fully elucidated. Pioglitazone improves NAFLD, whereas the underlying molecular mechanisms are not extensively clarified. In addition, cranberry and cinnamon have received increasing attention as potential therapeutic agents in metabolic disorders. Hence, this study aimed to test the hypothesis that the downregulation of HIF-1 alpha/TGF-beta 1/Smad/beta-catenin signaling might underlie the pioglitazone effect in HFD-induced liver steatosis in rats. In addition, the study aimed to determine whether the concurrent use of cranberry and/or cinnamaldehyde would boost biochemical and molecular gains of pioglitazone while limiting its significant side effect; weight gain. Rats were kept on a high-fat diet for 14 weeks, and HFD rats were orally treated with pioglitazone, cranberry, or their combinations for 8 weeks. Pioglitazone, cranberry, and to a lesser extent cinnamaldehyde significantly ameliorated the pathological lesions, improved the hepatic histological structure of cinnamaldehyde, and successfully rectified liver index, AST, ALT, lipid profile, hepatic triglycerides, and HOMA-IR. They also inhibited HIF-1 alpha, beta-catenin, TGF-beta 1 and subsequently inhibited phosphorylated/total Smad2/3 and their ratios. In conclusion, the beneficial effects of this combination in HFD-induced hepatic steatosis might be attributed to the modulation of hypoxia/HIF-1 alpha, TGF-beta 1/Smads, and Wnt/beta-catenin pathways in the liver. Thus, cranberry and cinnamon might be potential add-on agents to other pharmacotherapies in liver steatosis.

This study aimed to evaluate and compare the dried pomace powder of cranberries, lingonberries, sea buckthorns, and black currants as potential food ingredients with functional properties. The composition and several physicochemical and adsorption properties associated with their functionality were investigated. Tested berry pomace powders were rich in dietary soluble fiber (4.92-12.74 g/100 g DM) and insoluble fiber (40.95-65.36 g/100 g DM). The highest level of total phenolics was observed in the black currant pomace (11.09 GAE/g DM), whereas the sea buckthorn pomace revealed the highest protein concentration (21.09 g/100 g DM). All the berry pomace powders that were tested exhibited good water-holding capacity (2.78-4.24 g/g) and swelling capacity (4.99-9.98 mL/g), and poor oil-binding capacity (1.09-1.57 g/g). The strongest hypoglycemic properties were observed for the lingonberry and black currant pomace powders. The berry pomace powders presented effective in vitro hypolipidemic properties. The cholesterol-binding capacities ranged from 21.11 to 23.13 mg/g. The black currant and cranberry pomace powders demonstrated higher sodium-cholate-binding capacity than those of the lingonberry and sea buckthorn pomace powders. This study shows promising results that the powders of tested berry pomace could be used for further application in foods.