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Microbiome and metabolome alterations in Nrf2 knockout mice with induced gut inflammation and fed with phenethyl isothiocyanate and cranberry enriched diets

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Authors
Yin, Ran, Sargsyan, Davit, Wu, Ren-yi, Hudlikar, Rasika, Li, Shan-yi, Kuo, Hsiao-Chen, Sarwar, Md Shahid, Zhou, Yu-yin, Gao, Zhan, Howell, Amy, Chen, Chi, Blaser, Martin J., Kong, Ah-Ng
Journal
Molecular Nutrition & Food Research. 12 December 2025. 69(23).
Abstract

Cranberries contain phytochemicals with potent antioxidant properties. Phenethyl isothiocyanate (PEITC) is abundant in crucifers and possesses anti-cancer and anti-inflammatory properties. These food additives can alter gut microbiota and improve the host's health. Microbiome and microbial metabolome interactions with the host's cells help maintain gastrointestinal (GI) tract homeostasis. Cranberry and PEITC enriched diets were fed to wild-type (WT) and Nrf2 knockout (KO) mice, including those challenged with dextran sulfate sodium (DSS), and their gut microbiomes and metabolomes were examined. Relative abundances of Deferribacteres, Epsilonbacteraeota, and Proteobacteria decreased, while Firmicutes and Verrucomicrobia increased in the DSS-challenged mice samples. These trends were reversed by PEITC and cranberry enriched diets. The diets also preserved the Firmicutes-to-Bacteroidetes ratio, an endpoint associated with gut inflammation and obesity. DSS challenge altered production of several metabolites. Nrf2 KO mice samples had lower concentrations of short-chain fatty acids (SCFA) and amino acids, and higher concentrations of secondary bile acids. Nrf2 KO mice microbiomes exhibited higher richness and diversity. PEITC and cranberry enriched diets positively affected hosts' microbiomes and boosted several microbial metabolites. Phenotypic expression of Nrf2 impacted the microbiota and metabolic reprogramming induced by DSS-mediated inflammation and dietary supplements of cranberry and PEITC.

Microencapsulation of the polyphenolic fraction of cranberry fruit (Vaccinium oxycoccos) with coatings based on protein isolates: in vitro assessment of the bioavailability of polyphenolic compounds.

Posted
Authors
Zurek, Natalia, Kaliciak, Jagoda, Swieca, Michal, Kapusta, Ireneusz
Journal
Food and Bioproducts Processing. December 2025. 154:1-12.
Abstract

The aim of this study was to evaluate the effect of the type of protein used on the in vitro content and bioavailability of polyphenolic compounds from microcapsules with a cranberry polyphenolic core (CF). The effect of the carriers on the physicochemical properties of the microcapsules, swelling capacity in specific sections of the gastrointestinal tract, and safety of use was also examined by assessing biocompatibility with normal colonic epithelial cells. The microcapsules were prepared by ionotropic gelation using seven matrices: alginate (AL) and AL with whey protein isolate (WPI), pea protein isolate (PPI), soybean protein isolate (SPI), pumpkin protein isolate (PNPI), sunflower protein isolate (SNPI), and rice protein isolate (RPI). According to the results, all microcapsules demonstrated comparable and satisfactory properties in terms of dry weight, diameter, hygroscopicity, color, and biocompatibility. However, the choice of protein significantly influenced the values of other parameters. Microcapsules based on SPI provided the best process efficiency, while higher polyphenol content and antioxidant activity were observed for microcapsules containing SNPI and PNPI. In contrast, the highest bioavailability was estimated for microcapsules containing WPI. These findings could have significant implications for the design of new formulations and products for the food, nutraceutical, and pharmaceutical industries.

Nonantibiotic prophylaxis for urinary tract infections: a network meta-analysis of randomized controlled trials

Posted
Authors
Han Z, Yi X, Li J, Liao D, Ai J
Journal
Infection. 53(2):535-546, 2025 Apr
Abstract

OBJECTIVE: Recent guidelines indicated that, in addition to antibiotics, nonantibiotic interventions serve as available preventive options for urinary tract infections (UTIs). This study aimed to compare the efficacy and safety of various nonantibiotic interventions in preventing UTIs.

METHODS: The authors systematically searched databases for eligible studies. The inclusion criteria encompassed randomized controlled trials (RCTs) focusing on one or more nonantibiotic interventions for UTI prevention, with the incidence of UTIs being a key outcome measure. Subgroup analyses were performed according to age, sex, and follow-up.

RESULTS: 50 RCTs comprising 10,495 subjects and investigating 14 interventions, were included. Nearly 80% of the RCTs utilized double-blind or triple-blind designs. In the whole group, D-mannose (risk ratio [RR] 0.34, 0.21 to 0.56), vaccine (RR 0.65, 0.52 to 0.82), probiotics (RR 0.69, 0.50 to 0.94), cranberry (RR 0.72, 0.60 to 0.87), and triple therapy (cranberry plus probiotics plus vitamin A) (RR 0.27, 0.09 to 0.87), exhibited a significant reduction in UTI incidence compared to the placebo. Probiotics (RR 0.50, 0.28 to 0.89) were the most effective in the nonadult group, while vitamin D (RR 0.46, 0.27 to 0.81) showed the highest efficacy in the long follow-up group (>= 1 year). There was no significant difference in the incidence of adverse events between the interventions and the placebo group.

CONCLUSIONS: D-mannose, triple therapy, vaccine, probiotics, and cranberry serve as potential nonantibiotic intervention options for clinical UTI prevention.

Procyanidin A2, a polyphenol autophagy-enhancer, ameliorates hyperglycemia through multifaceted insulin-related mechanisms.

Posted
Authors
Song BR, Yoon SK, Lee CH, Alshammari FH, Yoo CY, Jeong KS, Lee DS, Lee SH
Journal
Scientific Reports. 15(1):41248, 2025
Abstract

Procyanidin A2 (PCA2), a flavonoid from cranberries and lingonberries, has shown various bioactivities, but its antidiabetic effects remain largely under-investigated. This study assessed PCA2's glucose-lowering potential through in silico, in vitro, and in vivo analyses. Molecular docking revealed strong binding of PCA2 to alpha-glucosidase (PDB: 3TOP), with competitive inhibition (IC50 = 3.62 +/- 0.841 microM). PCA2 was non-toxic up to 100 microM in C2C12 and INS-1 cells and enhanced glucose uptake via AMPK/AKT phosphorylation and GLUT4 expression. It also reduced oxidative stress and modulated autophagy-related proteins, increasing Beclin1, LC3-II, and Atg5 while decreasing p62. In diabetic mice, PCA2 improved glucose tolerance, protected beta-cells, and restored hepatic and muscular glycogen levels, as confirmed by H&E and PAS staining. Western blotting supported modulation of insulin signaling and autophagy. These findings suggest PCA2 as a promising candidate for functional foods targeting glucose regulation and metabolic dysfunctions.

Synergistic inhibition of Candida albicans by cranberry proanthocyanidins and probiotics: novel strategies for vulvovaginal candidiasis treatment

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Authors
Wu, Yu-Ru, Chen, Jung-Sheng, Chen, Lei-Chin, Chen, Laura, Huang, Yu-Fen, Liao, Chien-Sen
Journal
Pathogens. 24 March 2025. 14(4).
Abstract

Vulvovaginal candidiasis (VVC) is a common gynecological condition primarily caused by Candida albicans. The excessive use of antifungal drugs has led to increased drug resistance, necessitating the search for alternative therapies. This study investigates the synergistic antifungal effects of cranberry proanthocyanidins (PACs) and probiotics against C. albicans. PACs were prepared at different concentrations (low, medium, high) and tested alone and in combination with multi-strain probiotics, including Lactobacillus rhamnosus and Lactobacillus plantarum. The antifungal activity of their cell-free supernatants (CFS) was also assessed. The results demonstrated that the combination of L. plantarum and medium-concentration PACs (L.p. + PACs M) significantly enhance inhibition of C. albicans compared to individual treatments. In the Vaginal Microbiota Communities Analysis, this condition reduced C. albicans relative abundance to below 0.01%. This study highlights the potential of natural compounds and probiotics as alternative therapeutic strategies for VVC

Therapeutic Potential of Cranberry Proanthocyanidins in Addressing the Pathophysiology of Metabolic Syndrome: A Scrutiny of Select Mechanisms of Action

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Authors
Feldman F, Koudoufio M, Sané AT, Marcil V, Sauvé MF, Butcher J, Patey N, Martel C, Spahis S, Duan H, Figeys D, Desjardins Y, Stintzi A, Levy E.
Journal
Antioxidants 2025, 14(3), 268; https://doi.org/10.3390/antiox14030268
Abstract

Metabolic syndrome (MetS) constitutes a spectrum of interconnected conditions comprising obesity, dyslipidemia, hypertension, and insulin resistance (IR). While a singular, all-encompassing treatment for MetS remains elusive, an integrative approach involving tailored lifestyle modifications and emerging functional food therapies holds promise in preventing its multifaceted manifestations. Our main objective was to scrutinize the efficacy of cranberry proanthocyanidins (PAC, 200 mg/kg/day for 12 weeks) in mitigating MetS pathophysiology in male mice subjected to standard Chow or high-fat/high-fructose (HFHF) diets while unravelling intricate mechanisms. The administration of PAC, in conjunction with an HFHF diet, significantly averted obesity, evidenced by reductions in body weight, adiposity across various fat depots, and adipocyte hypertrophy. Similarly, PAC prevented HFHF-induced hyperglycemia and hyperinsulinemia while also lessening IR. Furthermore, PAC proved effective in alleviating key risk factors associated with cardiovascular diseases by diminishing plasma saturated fatty acids, as well as levels of triglycerides, cholesterol, and non-HDL-C levels. The rise in adiponectin and drop in circulating levels of inflammatory markers showcased PAC’s protective role against inflammation. To better clarify the mechanisms behind PAC actions, gut–liver axis parameters were examined, showing significant enhancements in gut microbiota composition, microbiota-derived metabolites, and marked reductions in intestinal and hepatic inflammation, liver steatosis, and key biomarkers associated with endoplasmic reticulum (ER) stress and lipid metabolism. This study enhances our understanding of the complex mechanisms underlying the development of MetS and provides valuable insights into how PAC may alleviate cardiometabolic dysfunction in HFHF mice.

A pilot study on the impact of cranberry and ascorbic acid supplementation on the urinary microbiome of healthy women: a randomized controlled trial.

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Authors
Nussbaumer-Proll, Alina, Hausmann, Bela, Weber, Maria, Pjevac, Petra, Berry, David, Zeitlinger, Markus
Journal
Antibiotics. 07 March 2025. 14(3).
Abstract

Background: The collection of microorganisms that colonize the human genital and urinary tract is referred to as the genitourinary microbiome. Urinary tract infections (UTIs), which predominantly affect women, are linked to alterations in the genitourinary microbiome. Cranberries (Vaccinium oxycoccos), rich in proanthocyanidins, and ascorbic acid (vitamin C), known for their urinary acidification properties, are commonly used for UTI prevention. However, their effects on the genitourinary microbiome remain inadequately characterized. This pilot study assesses the genitourinary microbiome composition in healthy women and evaluates the influence of cranberry and ascorbic acid supplementation. 

Methods: In a randomized, controlled, and open-label trial, 27 healthy women in their reproductive age (18-40 years) were assigned to three groups: cranberry (n = 8), ascorbic acid (n = 10), and control (n = 9). Urine samples were collected at three time points and processed for 16S rRNA gene amplicon-based microbial community composition analysis. Microbiome composition was compared within and between groups, and between study visits.

Results: Sufficient microbial DNA was extracted from all midstream urine samples. The genitourinary microbiome was predominantly composed of Lactobacillus spp., as reported previously. No significant shifts in microbial composition were observed in response to cranberry or ascorbic acid supplementation, and no statistically significant differences were detected between the intervention and control groups or between study visits. 

Conclusion: The genitourinary microbiome of healthy women remained stable during cranberry or ascorbic acid supplementation. Further studies in patients with recurrent UTIs are needed to explore the potential impacts of these supplements on the genitourinary microbiome in disease states.

Antimicrobial activity of cranberry juice (Vaccinium macrocarpon L.) ethanol extract against uropathogenic bacteria.

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Authors
Kaabi, Hayder Kamil Jabbar Al, Hmood, Baheeja A
Journal
Open Veterinary Journal. 28 February 2025. 15(2):813-819.
Abstract

Background: Cranberry fruit (Vaccinium macrocarpon L) contains a mixture of phytochemicals like flavonoids which consist of flavonoids, anthocyanins, proanthocyanidins, catechins, phenolic acids, and triterpenoids, all of which have possible antimicrobial (antibacterial, antifungal and antiviral) activity. Aim: This study aimed to determine the antibacterial effect of the ethanol extract of cranberry juice against uropathogen commonly found in urinary tract infections (UTIs) associated with pregnancy. 

Methods: Cranberry fruits were purchased from local markets and juiced, filtered, and dried. The dried powder was extracted with 70% ethanol for 8-10 days. The bacterial isolates used in this study (Escherichia coli, Proteus vulgaris, Staphylococcus aureus, Enterococcus sp., and Coagulase-Negative Staphylococci (CNS)) were collected from the Maternity and Children Hospital in Al-Diwaniyah City, Iraq. The antibacterial activity of the ethanol extract of cranberry juice was measured using a standard Disc diffusion method. Sterile paper discs were soaked in 20 micro L of different concentrations (12.5, 25, 50, and 100 mg/ml) of the extract, placed in Mueller-Hinton agar plates, and inoculated with bacterial cultures adjusted to 0.5 McFarland standards. Amoxicillin (30 micro g) was used as a positive control, and 70% ethanol was used as negative control. 

Results: The ethanol solution of cranberry juice displayed a significant (p < 0.05) inhibitory activity against all tested bacteria. The CNS showed the highest sensitivity with 100% inhibition, followed by S. aureus (90%), Enterococcus sp. (85%), P. vulgaris (75%), and E. coli (60%). The effect was dose dependent, as increasing the extract concentration resulted in broader inhibition zones. 

Conclusion: The results show that the ethanol extract of cranberry juice has potent antibacterial activity against uropathogenic bacteria, suggesting a possible role for cranberry juice ethanol extract in treating UTIs when combined with recently emerging facts about increasing antibiotic resistance.

Comparative Assessment of Efficacy of Cranberry Extract Mouthwash and Fluoride Mouthwash on Streptococcus mutans Count as an Adjunct to Conventional Caries Management among 6–12-year-old Children: A Randomized Controlled Trial

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Authors
Arushi Agrawal, Dimple Padawe, Vilas Takate, Sanath Kharat, Sanpreet S Sachdev
Journal
Int J Clin Pediatr Dent 2025;18(2):198–202.
Abstract

Background: Dental caries remains a prevalent oral health concern among children worldwide, necessitating effective preventive measures. This study evaluates the efficacy of cranberry extract mouthwash and fluoride mouthwashes in reducing Streptococcus mutans counts among children aged 6–12 years with moderate to severe dental caries. 

Materials and methods: A randomized controlled trial was conducted involving children with three or more carious lesions [Caries Assessment Spectrum and Treatment (CAST) types 3–9]. Participants were assigned to receive either cranberry extract mouthwash or fluoride mouthwash, administered weekly for 6 months. S. mutans colony-forming units (CFUs) were assessed at baseline, 3 months, and 6 months to measure bacterial load reduction. 

Results: Both cranberry extract mouthwash and fluoride mouthwashes demonstrated statistically significant reductions in S. mutans CFUs at 3 months (p < 0.01) and 6 months (p < 0.01) compared to baseline. No significant difference was observed between the two mouthwashes, suggesting comparable efficacy in bacterial count reduction. 

Conclusion: This study supports the use of cranberry extract mouthwash as a natural alternative to fluoride mouthwash in managing dental caries among children. Both interventions effectively reduced S. mutans counts, highlighting their potential as adjuncts to conventional caries management strategies.

Cranberry constituents prevent SOS-mediated filamentation of uropathogenic Escherichia coli.

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Authors
Prinster, Tracy, Harrison, Alistair, Dick, Christopher, Dennis J. Horvath, Jr, Li, Birong, Sievers, Grace, Madamsetty, Revanth, Zhang, Jingwen, Mason, Kevin M., Khoo, Christina, Justice, Sheryl S.
Journal
Infection and Immunity. 2025. 93(5).
Abstract

The diameter, length, and shape of bacteria are maintained with such high fidelity that these parameters are classically used as metrics in the distinction of bacterial species. Increasing evidence indicates that bacteria transiently shift their shapes into distinctive morphologies in response to environmental changes. Elongation of bacterial length into a filamentous shape provides unique survival advantages for many bacterial species. Analysis of 42 clinical isolates of uropathogenic Escherichia coli (UPEC) revealed that filamentation to host-derived antimicrobials is a conserved phenotype. Therefore, we hypothesize that filamentation represents a conserved mechanism of pathogenic bacterial persistence that can be targeted for narrow-spectrum, anti-virulence therapies. We demonstrate that cranberries prevent SulA-mediated filamentation of UPEC. Furthermore, we identify multiple fractions of cranberries that retain anti-filamentation properties. These studies provide mechanistic insight into the clinical efficacy of cranberry for patients with recurrent urinary tract infections. Inhibition of filamentation represents a novel approach to promote bacterial pathogen susceptibility to immune and antibiotic-mediated clearance to attenuate disease.