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Assessing the Gut Microbiota's Ability to Metabolize Oligomeric and Polymeric Flavan-3-ols from Aronia and Cranberry

Posted
Authors
Lessard-Lord, Jacob; Roussel, Charlene; Guay, Valerie; Desjardins, Yves
Journal
MOLECULAR NUTRITION & FOOD RESEARCH 10.1002/mnfr.202300641
Abstract

Clinical trials investigating the health effects of flavan-3-ols yield heterogeneous results due to interindividual variability in the gut microbiota metabolism. In fact, different groups in the population have similar metabolic profiles following (-)-epicatechin and (+)-catechin gut microbial metabolism and can be regrouped into so-called metabotypes. In this study, the capacity of 34 donors to metabolize polymeric B-type flavan-3-ols from aronia and oligomeric A-type flavan-3-ols from cranberry is investigated by in vitro fecal batch fermentations. Less than 1% of the flavan-3-ols from both sources are converted into microbial metabolites, such as phenyl-gamma-valerolactones (PVLs). To further confirm this result, gut microbial metabolites from flavan-3-ols are quantified in urine samples collected from participants, before and after a 4-day supplementation of cranberry extract providing 82.3 mg of flavan-3-ols per day. No significant difference is observed in the urinary excretion of flavan-3-ols microbial metabolites. Hence, it demonstrates by both in vitro and in vivo approaches that flavan-3-ols from aronia and cranberry are poorly degraded by the gut microbiota. The beneficial health impacts of these molecules likely stem from their capacity to affect gut microbiota and their interactions with the gut epithelium, rather than from their breakdown into smaller metabolites.

Berries in Microbiome-Mediated Gastrointestinal, Metabolic, and Immune Health

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Authors
Komarnytsky, Slavko; Wagner, Charles; Gutierrez, Janelle; Shaw, Odette M.
Journal
CURRENT NUTRITION REPORTS 10.1007/s13668-023-00449-0
Abstract

Purpose of Review: Current research has shown that berry-derived polymeric substrates that resist human digestion (dietary fibers and polyphenols) are extensively metabolized in the gastrointestinal tract dominated by microbiota. This review assesses current epidemiological, experimental, and clinical evidence of how berry (strawberry, blueberry, raspberry, blackberry, cranberry, black currant, and grapes) phytochemicals interact with the microbiome and shape health or metabolic risk factor outcomes.

Recent Findings: There is growing evidence that the compositional differences among complex carbohydrate fractions and classes of polyphenols define reversible shifts in microbial populations and human metabolome to promote gastrointestinal health. Interventions to prevent gastrointestinal inflammation and improve metabolic outcomes may be achieved with selection of berries that provide distinct polysaccharide substrates for selective multiplication of beneficial microbiota or oligomeric decoys for binding and elimination of the pathogens, as well as phenolic substrates that hold potential to modulate gastrointestinal mucins, reduce luminal oxygen, and release small phenolic metabolites signatures capable of ameliorating inflammatory and metabolic perturbations. These mechanisms may explain many of the differences in microbiota and host gastrointestinal responses associated with increased consumption of berries and highlight potential opportunities to intentionally shift gut microbiome profiles or to modulate risk factors associated with better nutrition and health outcomes.

Berry Dietary Interventions in Metabolic Syndrome: New Insights

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Authors
Venturi, Samuele; Marino, Mirko; Cioffi, Iolanda; Martini, Daniela; Del Bo', Cristian; Perna, Simone; Riso, Patrizia; Klimis-Zacas, Dorothy; Porrini, Marisa
Journal
NUTRIENTS 10.3390/nu15081906
Abstract

Metabolic Syndrome (MetS) is characterized by a group of dysmetabolic conditions, including abdominal obesity, dyslipidemia, glucose intolerance and/or insulin resistance, and hypertension. Generally, MetS is accompanied by an exacerbation of oxidative stress, inflammation, and vascular dysfunction. Increasing evidence suggests that berries and berry bioactives could play a potential role in the prevention and mitigation of the risk factors associated with MetS. The present systematic review summarizes the more recently available evidence deriving from human intervention studies investigating the effect of berries in subjects with at least three out of five MetS parameters. The PubMed, Scopus, and Embase databases were systematically searched from January 2010 until December 2022. A total of 17 human intervention trials met the inclusion criteria. Most of them were focused on blueberry (n = 6), cranberry (n = 3), and chokeberry (n = 3), while very few or none were available for the other berries. If considering MetS features, the main positive effects were related to lipid profile (low and high-density lipoproteins, cholesterol, and triglycerides) following blueberries and chokeberries, while conflicting results were documented for anthropometric parameters, blood pressure, and fasting blood glucose levels. Other markers analyzed within the studies included vascular function, oxidative stress, and inflammation. Here, the main positive effects were related to inflammation with a reduction in interleukin 6 and tumor necrosis factor-alpha following the intake of different berries. In conclusion, although limited, the evidence seems to support a potential role for berries in the modulation of lipid profile and inflammation in subjects with MetS. Furthermore, high-quality intervention trials are mandatory to demonstrate the role of berries in reducing risk factors for MetS and related conditions. In the future, such a demonstration could bring the adoption of berries as a potential dietary strategy to prevent/counteract MetS and related risk factors.

Biomarkers of Berry Intake: Systematic Review Update

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Authors
Mostafa, Hamza; Cheok, Alex; Merono, Tomas; Andres-Lacueva, Cristina; Rodriguez-Mateos, Ana
Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 10.1021/acs.jafc.3c01142
Abstract

Berries are rich in (poly)phenols, and these compounds may be beneficial to human health. Estimating berry consumption through self-reported questionnaires has been challenging due to compliance issues and a lack of precision. Estimation via food-derived biomarkers in biofluids was proposed as a complementary alternative. We aimed to review and update the existing evidence on biomarkers of intake for six different types of berries. A systematic literature search was performed to update a previous systematic review on PubMed, Web of Science, and Scopus from January 2020 until December 2022. Out of 42 papers, only18 studies were eligible. A multimetabolite panel is suggested for blueberry and cranberry intake. Proposed biomarkers for blueberries include hippuric acid and malvidin glycosides. For cranberries, suggested biomarkers are glycosides of peonidin and cyanidin together with sulfate and glucuronide conjugates of phenyl-& gamma;-valerolactone derivatives. No new metabolite candidates have been found for raspberries, strawberries, blackcurrants, and blackberries. Further studies are encouraged to validate these multimetabolite panels for improving the estimation of berry consumption.

Blueberry and cranberry extracts mitigate CCL4-induced liver damage, suppressing liver fibrosis, inflammation and oxidative stress

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Authors
Sergazy, Shynggys; Shulgau, Zarina; Kamyshanskiy, Yevgeniy; Zhumadilov, Zhaxybay; Krivyh, Elena; Gulyayev, Alexander; Aljofan, Mohamad
Journal
HELIYON 10.1016/j.heliyon.2023.e15370
Abstract

The current study aims to evaluate potential hepatoprotective effect of lingonberry, cranberry and blueberry polyphenols on carbon tetrachloride (CCL-4)-induced acute and subacute liver injury in rats. A total of 55 male Wistar rats, divided into six experimental and control groups. With the exception of the negative control group, all groups received an intraperitoneal injection of CCl-4, twice a week for 14 days. An extract of lingonberry, cranberry, blueberry polyphenols and the positive control, silymarin were administered daily via intragastric route, for 14 consecutive days. The untreated control group showed characteristic of classical oxidative stress-mediated liver damage with vacuolization of the hepatocyte cytoplasm, infiltration by immune cells and proliferation of collagen fibers, decrease in body weight and increase in liver weight; increased levels of AST and ALT in serum, an increased lipid peroxidation in the liver. However, the use of cranberry and blueberry polyphenols significantly suppressed liver damage, exerting an effect comparable to the hepatoprotective effect of the positive control. The extracts prevented and reduced inflammatory liver damage by reducing IL-6, TNF-alpha and IFN-gamma levels. In conclusion, blueberry and cranberry extracts have a protective effect against acute and subacute CCl4induced hepatotoxicity in rats.

Blueberry, cranberry, raspberry, and strawberry as modulators of the gut microbiota: target for treatment of gut dysbiosis in chronic kidney disease? From current evidence to future possibilities

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Authors
Coutinho-Wolino, Karen S.; Melo, Manuela F. S.; Mota, Jessica C.; Mafra, Denise; Guimaraes, Jonas T.; Stockler-Pinto, Milena B.
Journal
NUTRITION REVIEWS 10.1093/nutrit/nuad048
Abstract

Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is associated with uremic toxin production, inflammation, oxidative stress, and cardiovascular disease development. Therefore, healthy dietary patterns are essential modulators of gut microbiota. In this context, studies suggest that consuming berry fruits, rich in polyphenols and nutrients, may positively affect the gut microbiota, promoting the selective growth of beneficial bacteria and improving clinical status. However, studies on the effects of berry fruits on gut microbiota in CKD are scarce, and a better understanding of the possible mechanisms of action of berry fruits on gut microbiota is needed to guide future clinical studies and clinical practice in CKD. The objective was to discuss how berry fruits (blueberry, cranberry, raspberry, and strawberry) could be a therapeutic strategy to modulate the gut microbiota and possibly reverse the dysbiosis in CKD. Overall, available evidence shows that berry fruits can promote an increase in diversity by affecting the abundance of mucus-producing bacteria and short-chain fatty acids. Moreover, these fruits can increase the expression of mRNA involved in tight junctions in the gut such as occludin, tight junction protein 1 (TJP1), and mucin. Studies on the exact amount of berries leading to these effects show heterogeneous findings. However, it is known that, with 5 mg/day, it is already possible to observe some effects in animal models. Wild berries could possibly improve the uremic condition by reducing the levels of uremic toxins via modulation of the gut microbiota. In the long term, this could be an excellent strategy for patients with CKD. Therefore, clinical studies are encouraged to evaluate better these effects on CKD as well as the safe amount of these fruits in order to promote a better quality of life or even the survival of these patients.

Characteristics of Urinary Tract Infections and the Use of Cranberry Products in Patients With Urinary Diversions: A Narrative Review

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Authors
Droste, Linda R.; Ratliff, Catherine R.
Journal
JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING 10.1097/WON.0000000000001078
Abstract

PURPOSE: The aim of this narrative literature review was to summarize evidence regarding bacteriuria and urinary tract infections (UTIs) in patients living with a urinary diversion and the use of cranberry products for the prevention of these infections. 

METHODS: We searched for articles in the English language and available in full text to address the role of cranberry products in the management of UTIs in those with urinary diversions. We searched the electronic databases of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials between January 2003 and December 2023. Thirty-two elements were read in full and 9 elements that evaluated UTIs and/or the role of cranberries in preventing UTIs are included in this narrative review. 

RESULTS: Research indicates no significant difference in UTI rates, microbiology, or antibiotic sensitivity and resistance patterns between the different types of urinary diversions (orthoptic diversions, ileal conduit diversions, and continent cutaneous diversions). Similar to persons with an intact urinary tract, Escherichia coli (a prevalent coliform bacteria) was the most prevalent pathogen resulting in symptomatic UTIs. In addition, we found that E. coli strains persisted in urinary diversions involving reconstructed intestinal segments for prolonged periods of time despite antibiotic treatment. We found sparse evidence suggesting that cranberry products are effective for the prevention of UTIs after ileal conduit urinary diversion. 

CONCLUSIONS: There are inconsistencies in the definition of bacteriuria in the literature making it difficult to compare findings among the studies. Clinical guidance discussing the optimal method for obtaining a urine specimen from a urinary diversion and its management is limited. Research studies on the use of cranberry products to treat UTIs in persons living with a urinary diversion are urgently needed.

Chitosan Surface-Modified PLGA Nanoparticles Loaded with Cranberry Powder Extract as a Potential Oral Delivery Platform for Targeting Colon Cancer Cells

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Authors
Mostafa, Mona M. M.; Amin, Maha M. M.; Zakaria, Mohamed Y. Y.; Hussein, Mohammed Abdalla; Shamaa, Marium M. M.; Abd El-Halim, Shady M. M.
Journal
PHARMACEUTICS 10.3390/pharmaceutics15020606
Abstract

Nutraceutical cranberry powder extract (CBPE) has distinct polyphenols inhibiting colon cancer growth and proliferation. However, its oral therapeutic efficacy is hindered because of its low permeability. This study aims to formulate chitosan surface-modified PLGA nanoparticles (CS-PLGA NPs) for encapsulating CBPE and modulating its release rate, permeation, cell targeting, and, therefore, its cytotoxicity. A full 2(3) factorial design is employed to scrutinize the effect of lactide/glycolide ratio, PLGA weight, and stabilizer concentrations on entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formula (F4) shows spherical particles with a relatively high EE% (72.30 +/- 2.86%), an appropriate size of 370.10 +/- 10.31 nm, PDI; 0.398 +/- 0.001, and ZP; -5.40 +/- 0.21 mV. Alongside the ATR-FTIR outcomes, the chitosan surface-modified formula (CS-F4) demonstrates a significant increase in particle size (417.67 +/- 6.77 nm) and a shift from negative to positive zeta potential (+21.63 +/- 2.46 mV), confirming the efficiency of surface modification with chitosan. The intestinal permeability of F4 and CS-F4 is significantly increased by 2.19- and 3.10-fold, respectively, compared to the CBPE solution, with the permeability coefficient (P-app) being 2.05 x 10(-4) cm/min and 2.91 x 10(-4) cm/min, for F4 and CS-F4, respectively, compared to the CBPE solution, 9.36 x 10(-5) cm/min. Moreover, CS-F4 evidences significant caspase-3 protein level expression stimulation and significant inhibition of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription-3 (STAT-3) protein expression levels, confirming the superiority of CS-F4 for targeting HT-29 cells. Briefly, CS-PLGA NPs could be regarded as a prosperous delivery system of CBPE with enhanced permeation, cell targeting, and antitumor efficacy.

Comparative clinical evaluation of a local drug delivery of cranberry and garcinia fruit gel with tetracycline fibers for amelioration of periodontitis: A split mouth study.

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Authors
Panda, Vandana; Patidar, Pragya; Gaikwad, Rajesh; Borade, Shrutika; Fernandes, Lynette
Journal
Journal of Indian Society of Periodontology 10.4103/jisp.jisp_393_22
Abstract

Background: The present study formulates and evaluates a polyberry gel comprising extracts of cranberry (Vaccinium macrocarpon) and brindle berry (Garcinia cambogia) in patients suffering from chronic periodontitis.

Materials and Methods: The polyberry gel was evaluated for various physicochemical parameters, in vitro permeability and stability, and the active phytoconstituents were quantified by High-performance thin layer chromatography (HPTLC). Total phenolic content, total antioxidants, and ascorbic acid were estimated in the two extracts by in vitro assays. Patients suffering from chronic periodontitis with probing pocket depth (PPD) up to 5 mm were divided into 3 groups of 21 patients each and treated with scaling and root planing (SRP) or SRP followed by subgingival placement of polyberry gel or tetracycline fibers (standard). Plaque Index (PI), Gingival Index (GI), PPD, Clinical Attachment Level (CAL), and the salivary aspartate aminotransferase (AST) and C-reactive protein (CRP) levels were recorded at baseline and after 1 month.

Results: A significant (P < 0.01) reduction in the periodontic disease parameters was observed in the standard and gel-treated groups between their baseline and 1-month time-interval readings. The polyberry gel treatment significantly (P < 0.05 for AST and P < 0.01 for the rest) attenuated the periodontitis-elevated PI, GI PPD, CAL, AST and CRP levels when compared with SRP at the end of the study and was comparable with tetracycline.

Conclusion: The amelioration of periodontitis and gingival inflammation may be attributed to the potent antioxidant activity of the polyphenolic phytoconstituents of the gel. The polyberry gel may thus be used as a safe adjunct to SRP/tetracycline in chronic periodontitis.

Comparative evaluation of cranberry extract and sodium fluoride as mouth rinses on S. mutans counts in children: a double-blind randomized controlled trial

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Authors
Bansal, K.; Shamoo, A.; Mohapatra, S.; Kalaivani, M.; Batra, P.; Mathur, V. P.; Srivastava, A.; Chaudhry, R.
Journal
EUROPEAN ARCHIVES OF PAEDIATRIC DENTISTRY 10.1007/s40368-024-00939-x
Abstract

Background: Recently, research in the field of caries prevention is emphasizing upon identification of edible non-toxic compounds that can interfere with the formation of cariogenic biofilm. 

Aim: This trial aimed to assess the effectiveness of non-dialyzable material (NDM) containing cranberry mouth rinse (C-MR) on the Streptococcus mutans (S. mutans) counts and compare with that of a sodium fluoride (F-MR) mouth rinse. 

Methods: 280 children (8-12 years old) were enrolled in this double-blind single center, parallel, one-month, IRB/IEC approved non-inferiority trial. The participants fulfilling the inclusion criteria were randomly allocated into one of the two groups: C-MR and F-MR. All participants were given verbal and written instructions about at-home mouth-rinsing regimen under parental supervision for a month. Dental plaque samples were collected before and after a month of mouth-rinsing and subjected to culture techniques. S. mutans counts were assessed and compared in both groups. Primary outcome was the difference in the S. mutans counts between two interventions. Both intention-to-treat (ITT) and per-protocol analysis were carried out using two-sample t test with equal variance. 

Results: The mean S. mutans counts (after log transformation) in C-MR group were: 14.66 (90% CI 14.4,14.9) at baseline and 12.85 (90% CI 12.5, 13.2) colony-forming units/ml (CFU/ml) at one-month post intervention (p = 0.001); while these counts were 14.69 (90% CI 14.5, 14.9) at baseline and 12.71 (90% CI 12.3, 13.1) at one-month intervention in F-MR groups (p = 0.001). ITT analysis showed an inter- group difference of 0.14 CFU/ml (90% CI - 0.32,0.59) in post-SM counts between groups (p = 0.629). 

Conclusion: The study demonstrated that the cranberry mouth rinse was non-inferior to the fluoride mouth rinse in terms of S. mutans levels change. Cranberry-based mouth rinse can be used effectively to reduce the S. mutans counts in children. Trial registrationRegistration number in case of Clinical Trials-CTRI/2019/05/019395.