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Cranberry constituents prevent SOS-mediated filamentation of uropathogenic Escherichia coli

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Authors
Prinster T, Harrison A, Dick C, Horvath DJ Jr, Li B, Sievers G, Madamsetty R, Zhang J, Mason KM, Khoo C, Justice SS.
Journal
Infect Immun. 2025 Apr 10:e0060024. doi: 10.1128/iai.00600-24. Epub ahead of print. PMID: 40208062
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.

Whole cranberry fruit powder supplement reduces the incidence of culture-confirmed urinary tract infections in females with a history of recurrent urinary tract infection: A 6-month multicenter, randomized, double-blind, placebo-controlled trial

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Authors
Stonehouse W, Benassi-Evans B, Bednarz J, Vincent AD.
Journal
Am J Clin Nutr. 2025 Jan 23:S0002-9165(25)00022-X. doi: 10.1016/j.ajcnut.2025.01.022. Epub ahead of print. PMID: 39863114.
Abstract

Background High prevalence of urinary tract infections (UTI), including cystitis, and concern for antimicrobial resistance justify safe and effective nonantibiotic therapies for prevention of recurrent UTI (rUTI). 

Objectives This study investigated the effect of a whole cranberry fruit powder supplement on incidence of culture-confirmed UTI (primary outcome) in females with rUTI history. 

Methods This multicenter, 6-mo, randomized, placebo-controlled, double-blind study enrolled 150 healthy females [18–65 y, body mass index (BMI) >17.5 and <35 kg/m2] with rUTI defined as ≥3 UTIs in the last year or ≤2 UTIs in the last 6 mo, excluding those with >5 UTIs in the last 6 mo. Participants consumed either 1 capsule of 500 mg/d of whole cranberry powder (Pacran) or placebo. Culture-confirmed UTIs (>108cfu/L) were assessed throughout the intervention period at unscheduled clinic visits whenever participants experienced UTI symptoms and at baseline, 3- and 6-mo clinic visits. Symptomatic suspected UTIs were defined as participant-reported UTI-associated symptoms at unscheduled visits. 

Results Whole cranberry powder capsules reduced culture-confirmed UTI risk compared with placebo by 52% (adjusted relative risk [RR]: 0.48; 95% confidence interval [CI]: 0.26, 0.87; P = 0.01); reduced Escherichia coli UTIs (RR: 0.49; 95% CI: 0.24, 1.01; P = 0.05); reduced incidence of UTI with urinary frequency and urgency symptomatology (RR: 0.29; 95% CI:0.13, 0.63; P < 0.01); delayed time to first UTI episode (adjusted hazard ratio [HR]: 0.36; 95% CI: 0.18, 0.74; P = 0.01); and reduced the mean total number of UTIs per participant (adjusted incidence rate ratio IRR: 0.41; 95% CI: 0.21, 0.79; P = 0.01). Significant differences between groups in incidence of symptomatic suspected UTIs and culture-confirmed dysuria were not observed. Exploratory scores for UTI-related female sexual matters, assessed in a subset of sexually active, consenting females, did not differ significantly between groups. No safety concerns were reported. 

Conclusion This study shows that whole cranberry powder capsules do not impact safety markers and reduce the incidence of culture-confirmed UTI and several other UTI-related outcomes in healthy females with rUTI history.

Associations of breakfast cereal consumption with all-cause and cause-specific mortality: a large-scale prospective analysis

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Authors
Lin Z, Zeng M, Sui Z, Wu Y, Zhang H, Liu T.
Journal
Nutr J. 2025 Mar 24;24(1):48. doi: 10.1186/s12937-025-01109-5. PMID: 40128757; PMCID: PMC11934668
Abstract

Background: Previous studies have explored the relationship between breakfast cereal consumption and mortality risk, but these studies reported inconsistent findings and did not distinguish between consumers of different breakfast cereal types. This prospective cohort study aims to elucidate the dose-response relationship between specific breakfast cereal types and mortality risk. 

Methods: A total of 186,168 participants aged 40 to 69 years from UK Biobank that completed at least one online 24-hour dietary recall questionnaire and reported information on breakfast cereal consumption were included. Self-reported types and amounts of dietary breakfast cereal intake, and mortality from CVD (cardiovascular disease), cancer, and all causes were estimated. Cox regression analyses were employed to illustrate the correlation between the daily intake of different breakfast cereal types and mortality risk. 

Results: During a median follow-up of 13.4 years, 9402 deaths were recorded (including 5073 cancer deaths and 1687 CVD deaths). The intake of muesli was significantly correlated with reduced all-cause mortality, with the HRs (hazard ratios) (95% CIs) being 0.89 (0.83-0.95) (> 0-0.5 bowls/d) and 0.85 (0.79-0.92) (> 0.5-1 bowls/d), respectively. Bran cereal consumption also exhibited inverse correlations with all-cause mortality, showing an HR of 0.88 (95% CI: 0.81-0.95) (> 0-0.5 bowls/d) and 0.88 (95% CI: 0.80-0.98) (> 0.5-1 bowls/d). Moderate intake of porridge (> 0.5-1 bowls/day) was correlated with a reduced risk of all-cause mortality, with an HR (95% CI) of 0.89 (0.84-0.96). Furthermore, moderate consumption of muesli and bran cereal correlated with reduced mortality risks related to CVD and cancer, while plain cereal intake was correlated with increased CVD-specific mortality risk, and sweetened cereal consumption was correlated with elevated cancer-specific mortality risk. Additionally, participants who reported adding dried fruit to their breakfast cereals exhibited significantly lower risks of all-cause mortality and cause-specific mortality, and those who added milk to their breakfast cereals had a reduced risk of all-cause mortality. 

Conclusions: The findings support the moderate intake of several breakfast cereal types, including porridge, bran cereal, and muesli, as part of a healthy diet, while oat crunch and sweetened cereal consumption should be reduced to lower premature mortality risk.

Metabolic profile of procyanidin A2 by human intestinal microbiota and their antioxidant and hypolipidemic potential in HepG2 cells.

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Authors
He L, Yang G, Li T, Li W, Yang R.
Journal
Eur J Nutr. 2025 Mar 8;64(3):113. doi: 10.1007/s00394-025-03638-5. PMID: 40056191.
Abstract

Purpose: Procyanidins have strong potential for antioxidation and decreasing hepatic fat accumulation thus preventing non-alcoholic fatty liver disease (NAFLD). Procyanidin A2 (PCA2), predominately found in cranberries, avocado, peanut red skins and litchi fruit pericarp, is poorly absorbed in the gastrointestinal tract. However, literatures about its metabolic profile by gut microbiota and effects on lipid metabolism are limited. Therefore, the metabolites of PCA2 by human intestinal microbiota as well as their antioxidant and hypolipidemic potential were investigated. 

Methods: PCA2 was incubated with human intestinal microbiota and the metabolites produced were characterized by UPLC-Q-TOF-MS. The antioxidant and hypolipidemic potential of PCA2 and its microbial metabolites (MPCA2) were evaluated and compared. 

Results: The metabolism of PCA2 resulted in the formation of 14 metabolites, and the highest antioxidant capacity values were reached after 6 h incubation. In addition, PCA2 and MPCA2 were effective in reducing oxidative stress and lipid accumulation induced by oleic acid (OA) in HepG2 cells. They significantly promoted the phosphorylation of AMP-activated protein kinase (AMPK) and thus stimulated hepatic lipolysis by up-regulating of the expression of carnitine palmitoyl transferase I (CPT-I) and suppressed hepatic lipogenesis by down-regulation of the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA) reductase, fatty acid synthase (FAS) and sterol regulatory element binding proteins 1c (SREBP-1c). 

Conclusion: Our results indicated that PCA2 and MPCA2 were effective to prevent OA-induced lipid accumulation and oxidative stress in HepG2 cells, implying that microbial metabolites may play a crucial role in the realization of human health effects of PCA2.

Ex vivo oral biofilm model for rapid screening of antimicrobial agents including natural cranberry polyphenols

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Authors
Adami GR, Li W, Green SJ, Kim EM, Wu CD.
Journal
Sci Rep. 2025 Feb 19;15(1):6130. doi: 10.1038/s41598-025-87382-0. PMID: 39971954; PMCID: PMC11840115.
Abstract

The search has been ongoing for safe and effective antimicrobial agents for control and prevention of oral biofilm associated with disease. Clinical trials for oral specific anti-bacterials are costly and often provide inconclusive results. The simple approach of ex vivo testing of these agents has not demonstrated utility, likely due to variability of effects observed even with a single donor. We show how shed oral biofilms, easily obtained from donor saliva, and tested under optimized conditions, respond reproducibly to anti-bacterial challenges measured by reductions in rRNA accumulation in susceptible taxa. Responses are in part donor specific, but many bacteria taxa were shown to be reproducibly susceptible over a group of donors. For two antibiotics, vancomycin and penicillin G tested at pharmacologic levels, a subset of Gram-positive bacteria was inhibited. A natural product with antibacterial properties, diluted Vaccinium macrocarpon (cranberry) juice, was shown to inhibit a range of oral taxa, including Alloprevotella sp__HMT_473, Granulicatella adiacens, Lachnoanaerobaculum umeaense, Lepotrichia sp__HMT_215, Peptostreptococcus stomatis, Prevotella nanceiensis, Stomatobaculum sp__HMT_097, Veillonella parvula, and kill some targets. The model discussed in this study has promise as a rapid, precise, and reproducible ex vivo method to test and identify potential clinically useful antimicrobial agents active against the oral biofilm community.

Health-Improving Effects of Polyphenols on the Human Intestinal Microbiota: A Review

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Authors
Nemzer BV, Al-Taher F, Kalita D, Yashin AY, Yashin YI
Journal
Int J Mol Sci. 2025 Feb 5;26(3):1335. doi: 10.3390/ijms26031335. PMID: 39941107; PMCID: PMC11818678
Abstract

Dietary polyphenols are garnering attention in the scientific community due to their potential health-beneficial properties and preventative effects against chronic diseases, viz. cardiovascular diseases, diabetes, obesity, and neurodegenerative diseases. Polyphenols are antioxidants that change microbial composition by suppressing pathogenic bacteria and stimulating beneficial bacteria. The interaction of polyphenols with dietary fibers affects their bioaccessibility in the upper and lower parts of the digestive tract. Dietary fibers, polyphenols, their conjugates, and their metabolites modulate microbiome population and diversity. Consuming polyphenol-rich dietary fibers such as pomegranate, cranberry, berries, and tea improves gut health. A complex relationship exists between polyphenol-rich diets and gut microbiota for functioning in human health. In this review, we provide an overview of the interactions of dietary polyphenols, fibers, and gut microbiota, improving the understanding of the functional properties of dietary polyphenols.

Association of the newly proposed dietary index for gut microbiota and constipation: a cross-sectional study from NHANES

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Authors
Zhang Z, Bi C, Wu R, Qu M.
Journal
Front Nutr. 2025 Jan 17;12:1529373. doi: 10.3389/fnut.2025.1529373. PMID: 39895839; PMCID: PMC11782033
Abstract

Objective The dietary index for gut microbiota. DI-GM is an innovative metric designed to capture the diversity of the gut microbiome, yet its association with constipation remains unstudied. 

Methods In this cross-sectional study, 11,405 adults aged 20 and older were selected from the National Health and Nutrition Examination Survey 2005–2010 for the sample. Constipation was defined as fewer than three defecation frequencies per week using bowel health questionnaire (BHQ). Fewer than three bowel movements per week were considered as constipation by Bowel Health Questionnaire (BHQ). DI-GM was derived from dietary recall data, including avocado, broccoli, chickpeas, coffee, cranberries, fermented dairy, fiber, green tea, soybean and whole grains as beneficial elements, red meat, processed meat, refined grains, and high fat as detrimental components. Multivariable weighted logistic was employed to investigate the association of DI-GM with constipation. Secondary analyses included subgroup analyses, restricted cubic spline (RCS), and multiple imputation. 

Results A higher DI-GM and beneficial gut microbiota score were associated with a lower prevalence of constipation (DI-GM: OR = 0.82, 95% CI = 0.75, 0.90; beneficial gut microbiota score: OR = 0.77, 95% CI = 0.67, 0.89). After grouping DI-GM, in the fully adjusted model, participants with DI-GM ≥ 6 were significantly negatively correlated with both the prevalence of constipation (OR = 0.48, 95% CI = 0.33, 0.71). RCS indicated a non-linear relationship between DI-GM and constipation. Subgroup analyses by age, sex and common complications showed no statistically significant interactions (p > 0.05). 

Conclusion The newly proposed DI-GM was inversely related with the prevalence of constipation. When treating patients with constipation, it is necessary for clinicians to provide timely and effective dietary interventions incorporating the DI-GM for patients with constipation to avoid further deterioration of the condition.

Edible Berries-An Update on Nutritional Composition and Health Benefits-Part II

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Authors
Thorakkattu P, Jain S, Sivapragasam N, Maurya A, Tiwari S, Dwivedy AK, Koirala P, Nirmal N.
Journal
Curr Nutr Rep. 2025 Jan 3;14(1):10. doi: 10.1007/s13668-024-00608-x. PMID: 39753836.
Abstract

Purpose of review: Berries are a great source of fiber, polyunsaturated fatty acids, and beneficial secondary metabolites (polyphenols). Various phytochemicals present in berries (glycosidic-linked flavonoids, anthocyanins, etc.) provide potential health benefits to consumers. Berries are known as high antioxidant food which provides certain cellular and molecular protection thereby lower rates of obesity and chronic disease risk. Molecular-level mechanisms protect a cell, while cellular mechanism considers all molecular units. For example, polyphenols found in blueberries have the potential to significantly reduce adipogenesis. Therefore, in continuation with part I, this review part II summarizes recent updates on the nutritional composition and biological activities of caperberry, chokeberry, cloudberry, cranberry, elderberry, gooseberry, goji berry, and lingonberry. 

Recent findings: These berries contain higher amounts of dietary fiber, protein, polyphenols, vitamins, minerals, and lipids. Besides, their antioxidant and anti-inflammatory activities, these berries are reported for eye health, brain health, cardiovascular health, anti-diabetic, etc. The consumption of a summarized group of berries could be more beneficial for eye health, mental health, and metabolic health thereby enhancing the well-being of the consumers.

Polyphenol-rich cranberry beverage positively affected skin health, skin lipids, skin microbiome, inflammation, and oxidative stress in women in a randomized controlled trial.

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Authors
Christman, Lindsey, de Benedetto, Anna, Johnson, Elizabeth, Khoo, Christina, Gu, Li-wei
Journal
Nutrients 16 September 2024. 16(18). 53 ref.
Abstract

This study aimed to determine whether a polyphenol-rich cranberry beverage affects skin properties, lipids, and the microbiome in women using a randomized, double-blinded, placebo-controlled, cross-over design. Twenty-two women with Fitzpatrick skin types 2-3 were randomized to drink a cranberry beverage or placebo for six weeks. After a 21-day washout, they consumed the opposite beverage for six weeks. Six weeks of cranberry beverage significantly reduced UVB-induced erythema, improved net elasticity on the face and forearm, smoothness on the face, and gross elasticity on the forearm compared to the placebo. When stratified by age, these effects of the cranberry beverage were primarily observed in women >40 years old. SOD activities were improved after six weeks of cranberry beverage consumption compared to the placebo, while glutathione peroxide and TNF- alpha were improved compared to baseline. These effects were found to differ by age group. Skin lipid composition was modulated by both the cranberry beverage and the placebo. Cranberry beverages did not change alpha - or beta -diversity but altered the abundance of several skin microbes at the species and strain level. Consumption of a cranberry beverage for six weeks improved specific skin properties and oxidative stress and modulated skin lipids and microbiome compared to placebo.

A multiomics evaluation of the countermeasure influence of 4-week cranberry beverage supplementation on exercise-induced changes in innate immunity.

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Authors
Nieman, David C., Sakaguchi, Camila A., Williams, James C., Woo, Jongmin, Omar, Ashraf M., Mulani, Fayaj A., Zhang, Qi-bin, Pathmasiri, Wimal, Rushing, Blake R., McRitchie, Susan, Sumner, Susan J., Lawson, Jackie, Lambirth, Kevin C.
Journal
Nutrients 26 September 2024. 16(19). 57 ref.
Abstract

Objectives: This study examined the effect of a 4-week unsweetened cranberry beverage (CRAN) (317 mg polyphenols) versus placebo beverage (PLAC) ingestion (240 mL/day) on moderating exercise-induced changes in innate immunity. 

Methods: Participants included 25 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind crossover design was used with two 4-week supplementation periods and a 2-week washout period. Supplementation periods were followed by an intensive 2.25 h cycling bout. Six blood samples were collected before and after supplementation (in an overnight fasted state) and at 0 h, 1.5 h, 3 h, and 24 h post-exercise. Stool and urine samples were collected pre- and post-supplementation. Outcome measures included serum creatine kinase, myoglobin, and cortisol, complete blood counts, plasma untargeted proteomics, plasma-targeted oxylipins, untargeted urine metabolomics, and stool microbiome composition via whole genome shotgun (WGS) sequencing. 

Results: Urine CRAN-linked metabolites increased significantly after supplementation, but no trial differences in alpha or beta microbiota diversity were found in the stool samples. The 2.25 h cycling bout caused significant increases in plasma arachidonic acid (ARA) and 53 oxylipins (FDR q-value < 0.05). The patterns of increase for ARA, four oxylipins generated from ARA-cytochrome P-450 (CYP) (5,6-, 8,9-, 11,12-, and 14,15-diHETrEs), two oxylipins from linoleic acid (LA) and CYP (9,10-DiHOME, 12,13-DiHOME), and two oxylipins generated from LA and lipoxygenase (LOX) (9-HODE, 13-HODE) were slightly but significantly higher for the CRAN versus PLAC trial (all interaction effects, p < 0.05). The untargeted proteomics analysis showed that two protein clusters differed significantly between the CRAN and PLAC trials, with CRAN-related elevations in proteins related to innate immune activation and reduced levels of proteins related to the regulation of the complement cascade, platelet activation, and binding and uptake of ligands by scavenger receptors. No trial differences were found for cortisol and muscle damage biomarkers. 

Conclusion: CRAN versus PLAC juice resulted in a significant increase in CRAN-related metabolites but no differences in the gut microbiome. CRAN supplementation was associated with a transient and modest but significant post-exercise elevation in selected oxylipins and proteins associated with the innate immune system.