Background and aim: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection. 

Methods: This double‐blind, randomized, placebo‐controlled trial on 522 H. pylori‐positive adults evaluated dose–response effects of proanthocyanidin‐standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by 13C‐urea breath testing and eradication at 45 days post‐intervention. 

Results: H. pylori‐negative rates in placebo, low‐proanthocyanidin, medium‐proanthocyanidin, and high‐proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high‐proanthocyanidin juice twice daily (44 mg proanthocyanidin/240‐mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori‐negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well‐tolerated. 

Conclusions: Twice‐daily consumption of proanthocyanidin‐standardized cranberry juice may help potentiate suppression of H. pylori infection. Trial registration: ChiCTR1800017522, per WHO ICTRP. 

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 a 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.

Cranberry-derived proanthocyanidin (PAC) is processed by the gut microbiota to produce 3-(4-hydroxyphenyl)-propionic acid (HPPA), among other metabolites. These data are in support of the article entitled, "Cranberry proanthocyanidin and its microbial metabolite 3,4-dihydroxyphenylacetic acid, but not 3-(4-hydroxyphenyl)-propionic acid, partially reverse pro-inflammatory microRNA responses in human intestinal epithelial cells," published in Molecular Nutrition and Food Research [1]. Here we describe data generated by nCounterⓇ Human v3 miRNA Expression Panel of RNA obtained from Caco-2BBe1 cells exposed to two different concentrations of cranberry extract rich in PAC (50 µg/ml or 100 µg/ml) or 3-(4-hydroxyphenyl)-propionic acid (5 µg/ml or 10 µg/ml) for 24 h, then stimulated with 1 ng/ml of IL-1ß or not (mock) for three hours. The raw data are publicly available at the NCBI GEO database GSE237078. This work also includes descriptive methodological procedures, treatment-responsive microRNA (miRNA) expression profiles in Caco-2BBe1 cells, and in silico mRNA gene target and pathway enrichment analyses of significantly differentially expressed miRNAs (q < 0.001). Cranberry and its components have recognized health benefits, particularly in relation to combatting inflammation and pathogenic bacterial adhesion. These data will be valuable as a reference to study the response of intestinal cells to other polyphenol-rich food sources, analyze gut microbial responses to cranberry and its metabolites in different cell lines and mammalian hosts to elucidate individualized effects, and to delineate the role of the gut microbiota in facilitating the benefits of cranberry. Moreover, these data will aid in expanding our knowledge on the mechanisms underlying the benefits of cranberry and its components.

(Research funded in part by Ocean Spray Cranberries, Inc.)

Objectives: Polyphenol compounds are classified as organic compounds with phenolic units exhibiting a variety of biological functions. This meta-analysis aims to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating Helicobacter pylori. 

Design: Systematic review and meta-analysis. 

Methods: Literature searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal Database and Wan Fang database from inception to January 2022. All randomised controlled trials comparing polyphenol compounds with the placebo or used as an adjunct treatment are included in this meta-analysis. The treatment effect for dichotomous outcomes was assessed using risk ratio (RR), while for continuous outcomes, mean differences both with 95% CIs, were used. Subgroup analyses were carried out for different treatment schemes and polyphenol compound species. 

Results: 12 trials were included in the meta-analysis. The total eradication rate of H.pylori in the polyphenol compounds group was higher than in the group without polyphenol compounds. Statistical significance was also observed (RR 1.19, 95%CI 1.03 to 1.38, p=0.02). The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the two groups (RR 1.47, 95%CI 0.83 to 2.58, p=0.18). In subgroup analyses, the H.pylori eradication rate regimens with polyphenols therapy was superior to that of regimens without polyphenols therapy in the polyphenols versus placebo subgroup (RR 4.23, 95%CI 1.38 to 12.95, p=0.01), polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95%CI 1.01 to 1.22, p=0.03). 

Conclusion: Polyphenol compounds can improve H.pylori eradication rates. Polyphenol compounds plus standard triple therapy can significantly improve the eradication. However, no evidence of a higher incidence of side effects could be found.

The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles. We conducted a literature review of longitudinal studies on the association of diet with gut microbiota in adult populations and extracted those dietary components with evidence of beneficial or unfavorable effects. Dietary recall data from the National Health and Nutrition Examination Survey (NHANES, 2005–2010, n = 3812) were used to compute the DI-GM, and associations with biomarkers of gut microbiota diversity (urinary enterodiol and enterolactone) were examined using linear regression. From a review of 106 articles, 14 foods or nutrients were identified as components of the DI-GM, including fermented dairy, chickpeas, soybean, whole grains, fiber, cranberries, avocados, broccoli, coffee, and green tea as beneficial components, and red meat, processed meat, refined grains, and high-fat diet (≥40% of energy from fat) as unfavorable components. Each component was scored 0 or 1 based on sex-specific median intakes, and scores were summed to develop the overall DI-GM score. In the NHANES, DI-GM scores ranged from 0–13 with a mean of 4.8 (SE = 0.04). Positive associations between DI-GM and urinary enterodiol and enterolactone were observed. The association of the novel DI-GM with markers of gut microbiota diversity demonstrates the potential utility of this index for gut health-related studies.

Cranberries have known anti-inflammatory properties, which extend their benefits in the context of several chronic diseases. These benefits highly rely on the polyphenol profile of cranberries, one of few foods rich in A-type proanthocyanidin (PAC). A-type PAC comprises flavan-3-ol subunits with an additional interflavan ether bond in the conformational structure of the molecule, separating them from the more commonly found B-type PAC. PACs with a degree of polymerization higher than three are known to reach the colon intact, where they can be catabolyzed by the gut microbiota and biotransformed into lower molecular weight organic acids that are available for host absorption. Gut microbiota-derived metabolites have garnered much attention in the past decade as mediators of the health effects of parent compounds. Though, the mechanisms underlying this phenomenon remain underexplored. In this review, we highlight emerging evidence that postulates that polyphenols, including ones derived from cranberries, and their metabolites could exert anti-inflammatory effects by modulating host microRNAs. Our review first describes the chemical structure of cranberry PACs and a pathway for how they are biotransformed by the gut microbiota. We then provide a brief overview of the benefits of microbial metabolites of cranberry in the intestinal tract, at homeostasis and in inflammatory conditions. Finally, we discuss the role of microRNAs in intestinal health and in response to cranberry PAC and how they could be used as targets for the maintenance of intestinal homeostasis. Most of this research is pre-clinical and we recognize that conducting clinical trials in this context has been hampered by the lack of reliable biomarkers. Our review discusses the use of miRNA as biomarkers in this context.

BACKGROUND AND AIM: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection.

METHODS: This double-blind, randomized, placebo-controlled trial on 522 H. pylori-positive adults evaluated dose-response effects of proanthocyanidin-standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by 13 C-urea breath testing and eradication at 45 days post-intervention.

RESULTS: H. pylori-negative rates in placebo, low-proanthocyanidin, medium-proanthocyanidin, and high-proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high-proanthocyanidin juice twice daily (44 mg proanthocyanidin/240-mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori-negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well-tolerated.

CONCLUSIONS: Twice-daily consumption of proanthocyanidin-standardized cranberry juice may help potentiate suppression of H. pylori infection.

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.

Numerous health benefits have been reported from the consumption of cranberry-derived products, and recent studies have identified bioactive polysaccharides and oligosaccharides from cranberry pomace. This study aimed to further characterize xyloglucan and pectic oligosaccharide structures from pectinase-treated cranberry pomace and measure the growth and short-chain fatty acid production of 86 Lactobacillus strains using a cranberry oligosaccharide fraction as the carbon source. In addition to arabino-xyloglucan structures, cranberry oligosaccharides included pectic rhamnogalacturonan I which was methyl-esterified, acetylated and contained arabino-galacto-oligosaccharide side chains and a 4,5-unsaturated function at the non-reducing end. When grown on cranberry oligosaccharides, ten Lactobacillus strains reached a final culture density (Delta OD) >= 0.50 after 24 h incubation at 32 degrees C, which was comparable to L. plantarum ATCC BAA 793. All strains produced lactic, acetic, and propionic acids, and all but three strains produced butyric acid. This study demonstrated that the ability to metabolize cranberry oligosaccharides is Lactobacillus strain specific, with some strains having the potential to be probiotics, and for the first time showed these ten strains were capable of growth on this carbon source. The novel cranberry pectic and arabino-xyloglucan oligosaccharide structures reported here combined with the Lactobacillus strains that can metabolize cranberry oligosaccharides and produce short-chain fatty acids, have excellent potential as health-promoting synbiotics.

The consumption of plant-based bioactive compounds modulates the gut microbiota and interacts with the innate and adaptive immune responses associated with metabolic disorders. The present study aimed to evaluate the effect of cranberry polyphenols (CP), rich in flavonoids, and agavins (AG), a highly branched agave-derived neo-fructans, on cardiometabolic response, gut microbiota composition, metabolic endotoxemia, and mucosal immunomodulation of C57BL6 male mice fed an obesogenic high-fat and high-sucrose (HFHS) diet for 9 weeks. Interestingly, CP+AG-fed mice had improved glucose homeostasis. Oral supplementation with CP selectively and robustly (five-fold) increases the relative abundance of Akkermansia muciniphila, a beneficial bacteria associated with metabolic health. AG, either alone or combined with CP (CP+AG), mainly stimulated the glycan-degrading bacteria Muribaculum intestinale, Faecalibaculum rodentium, Bacteroides uniformis, and Bacteroides acidifaciens. This increase of glycan-degrading bacteria was consistent with a significantly increased level of butyrate in obese mice receiving AG, as compared to untreated counterparts. CP+AG-supplemented HFHS-fed mice had significantly lower levels of plasma LBP than HFHS-fed controls, suggesting blunted metabolic endotoxemia and improved intestinal barrier function. Gut microbiota and derived metabolites interact with the immunological factors to improve intestinal epithelium barrier function. Oral administration of CP and AG to obese mice contributed to dampen the pro-inflammatory immune response through different signaling pathways. CP and AG, alone or combined, increased toll-like receptor (TLR)-2 (Tlr2) expression, while decreasing the expression of interleukin 1ss (ILss1) in obese mice. Moreover, AG selectively promoted the anti-inflammatory marker Foxp3, while CP increased the expression of NOD-like receptor family pyrin domain containing 6 (Nlrp6) inflammasome. The intestinal immune system was also shaped by dietary factor recognition. Indeed, the combination of CP+AG significantly increased the expression of aryl hydrocarbon receptors (Ahr). Altogether, both CP and AG can shape gut microbiota composition and regulate key mucosal markers involved in the repair of epithelial barrier integrity, thereby attenuating obesity-associated gut dysbiosis and metabolic inflammation and improving glucose homeostasis.