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Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome

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Authors
Weh KM, Howard CL, Zhang Y, Tripp BA, Clarke JL, Howell AB, Rubenstein JH, Abrams JA, Westerhoff M, Kresty LA
Journal
JCI Insight. 2024 Feb 8;9(6):e168112. doi: 10.1172/jci.insight.168112. PMID: 38329812; PMCID: PMC11063939
Abstract

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett’s esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome–esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 μg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinisEscherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory, and immune-implicated proteins and genes, including Ccl4Cd14CrpCxcl1Il6Il1bLbpLcn2Myd88Nfkb1Tlr2, and Tlr4, aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.

Recurrent UTI in Women-Risk Factors and Management

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Authors
Lazarus JE, Gupta K
Journal
Infect Dis Clin North Am. 2024 Jun;38(2):325-341. doi: 10.1016/j.idc.2024.03.010. Epub 2024 Apr 10. PMID: 38599896
Abstract

Urinary tract infections (UTIs) are common in women; more than 50% of women will be diagnosed with a UTI in her lifetime. Many of these women will go on to develop recurrent UTI. Nevertheless, evidence-based prevention of recurrent UTI is under-utilized. Here, the authors provide detailed practical advice on UTI prevention with a thorough review of the evidence. Non-antibiotic prevention measures discussed include increased fluid intake, vaginal estrogen therapy, methenamine, and cranberry. Antibiotic prophyalxis for carefully selected patients is also discussed.

The Development and Evaluation of a Literature-Based Dietary Index for Gut Microbiota

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Authors
Kase BE, Liese AD, Zhang J, Murphy EA, Zhao L, Steck SE
Journal
Nutrients. 2024 Apr 3;16(7):1045. doi: 10.3390/nu16071045. PMID: 38613077; PMCID: PMC11013161
Abstract

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.

The Diagnosis, Treatment, and Prevention of Recurrent Urinary Tract Infection

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Authors
Schmiemann G, Kranz J, Mandraka F, Schubert S, Wagenlehner F, Gágyor I
Journal
Dtsch Arztebl Int. 2024 May 31;(Forthcoming):arztebl.m2024.0068. doi: 10.3238/arztebl.m2024.0068. Epub ahead of print. PMID: 38686602
Abstract

Background: Urinary tract infection has a one-year prevalence of 11% in women and ranges among the most common reasons for consulting a primary care physician and for receiving a prescription for antibiotics. In the case of recurrent urinary tract infection (rUTI), there are questions about the further work-up, treatment, and preventive measures.

Methods: The systematic literature search performed for the update of the German clinical practice guideline on uncomplicated urinary tract infection (043-044) (up to February 2022) was supplemented with a selective search for clinical trials (up to August 2023).

Results: Urine culture and ultrasonography are reasonable steps in the diagnostic evaluation of rUTI. Further invasive testing is suggested for men but is not routinely indicated for women. Antibiotics are among the most effective preventive measures (risk ratio [RR] 0.15, 95% confidence interval [0.1; 0.3]) but carry a high risk of side effects. Non-antibiotic preparations such as cranberry juice (RR 0.74 [0.5; 0.99]), mannose (RR 0.23 [0.14; 0.37]), and vaginal estrogen (RR, 0.42 [0.30; 0.59]) can also reduce the infection rate, with a low risk of side effects. Increased daily fluid intake has been shown to lower infection rates in the short term (odds ratio [OR] 0.13 [0.07; 0.25]); the use of hygienically advisable wiping techniques after passing stool or urine has been little studied but can be implemented with no risk.

Conclusion: rUTI poses a challenge for the treating physician. The measures to be taken must be considered on an individual basis. Vulnerable groups, such as older patients, need special attention.

The role of intestinal microbiota and microRNAs in the anti-inflammatory effects of cranberry: from pre-clinical to clinical studies

Posted
Authors
Taibi A, Lofft Z, Laytouni-Imbriaco B, Comelli EM
Journal
Front Nutr. 2023 May 23;10:1092342. doi: 10.3389/fnut.2023.1092342. PMID: 37287997; PMCID: PMC10242055
Abstract

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.

Uropathogenic Escherichia coli endeavors: an insight into the characteristic features, resistance mechanism, and treatment choice

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Authors
Arafi V, Hasani A, Sadeghi J, Varshochi M, Poortahmasebi V, Hasani A, Hasani R
Journal
Arch Microbiol. 2023 May 8;205(6):226. doi: 10.1007/s00203-023-03553-5. PMID: 37156886
Abstract

Uropathogenic Escherichia coli (UPEC) are the strains diverted from the intestinal status and account mainly for uropathogenicity. This pathotype has gained specifications in structure and virulence to turn into a competent uropathogenic organism. Biofilm formation and antibiotic resistance play an important role in the organism’s persistence in the urinary tract. Increased consumption of carbapenem prescribed for multidrug-resistant (MDR) and Extended-spectrum-beta lactamase (ESBL)-producing UPECs, has added to the expansion of resistance. The World Health Organization (WHO) and Centre for Disease Control (CDC) placed the Carbapenem-resistant Enterobacteriaceae (CRE) on their treatment priority lists. Understanding both patterns of pathogenicity, and multiple drug resistance may provide guidance for the rational use of anti-bacterial agents in the clinic. Developing an effective vaccine, adherence-inhibiting compounds, cranberry juice, and probiotics are non-antibiotical approaches proposed for the treatment of drug-resistant UTIs. We aimed to review the distinguishing characteristics, current therapeutic options and promising non-antibiotical approaches against ESBL-producing and CRE UPECs.

Ursolic Acid against Prostate and Urogenital Cancers: A Review of In Vitro and In Vivo Studies

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Authors
Kornel A, Nadile M, Retsidou MI, Sakellakis M, Gioti K, Beloukas A, Sze NSK, Klentrou P, Tsiani E
Journal
Int J Mol Sci. 2023 Apr 18;24(8):7414. doi: 10.3390/ijms24087414. PMID: 37108576; PMCID: PMC10138876
Abstract

Prostate cancer is the second most diagnosed form of cancer in men worldwide and accounted for roughly 1.3 million cases and 359,000 deaths globally in 2018, despite all the available treatment strategies including surgery, radiotherapy, and chemotherapy. Finding novel approaches to prevent and treat prostate and other urogenital cancers effectively is of major importance. Chemicals derived from plants, such as docetaxel and paclitaxel, have been used in cancer treatment, and in recent years, research interest has focused on finding other plant-derived chemicals that can be used in the fight against cancer. Ursolic acid, found in high concentrations in cranberries, is a pentacyclic triterpenoid compound demonstrated to have anti-inflammatory, antioxidant, and anticancer properties. In the present review, we summarize the research studies examining the effects of ursolic acid and its derivatives against prostate and other urogenital cancers. Collectively, the existing data indicate that ursolic acid inhibits human prostate, renal, bladder, and testicular cancer cell proliferation and induces apoptosis. A limited number of studies have shown significant reduction in tumor volume in animals xenografted with human prostate cancer cells and treated with ursolic acid. More animal studies and human clinical studies are required to examine the potential of ursolic acid to inhibit prostate and other urogenital cancers in vivo. 

Evaluation of phenolic content in selected red fruit juices

Posted
Authors
Nieć-Leśniak J, Szczepańska E, Białek-Dratwa A, Kiciak A, Niewiadomska E.
Journal
Rocz Panstw Zakl Hig. 2024 Aug 14;75(2):125-134. doi: 10.32394/rpzh.2024.0298. Epub 2024 May 9. PMID: 39140118
Abstract

Background. Red fruits are characterised by a particularly high content of bioactive compounds, e.g. anthocyanins, tannins, pectins, vitamins and minerals. Dietary supply of proper amounts of antioxidants is essential to reduce oxidative stress, and thus is an important element in the prevention of lifestyle diseases. 

Objective. The aim of the study was to evaluate and compare the content of polyphenols in selected red fruit juices (chokeberry, elderberry, pomegranate, cranberry), as well as to assess the impact of storage time on the content of these compounds in the analysed samples. 

Material and Methods. The research material consisted of 17 juices (100%): 3 chokeberry juices, 4 elderberry juices, 5 pomegranate juices and 5 cranberry juices, which differed in terms of the manufacturer, type, price range, country of origin and production method. The total polyphenol content was measured by spectrophotometry using the FolinCiocalteu reagent. The procedure was based on a modified method described by Waterhouse. Active acidity (pH) was measured with the potentiometric method using a pH-meter and the sucrose content was measured using a refractometer. 

Results. The highest mean content of polyphenolic compounds was found in chokeberry and elderberry juices. Juice storage time did not reduce the mean content of polyphenolic compounds. The highest sucrose content was found in chokeberry juices and the lowest in cranberry juice. 

Conclusions. Chokeberry and elderberry juices had the highest content of polyphenols among the tested products. Juices stored after opening in accordance with the manufacturer’s instructions (at 4°C) do not lose their nutritional properties.

Alternative Approaches for the Management of Urinary Tract Infection with Crano-cure: A Randomized Clinical Trial

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Authors
Ur Rehman J, Iqbal A, Asif HM, Hadi F, Ahmed K, Ahmed M, Sumreen L.
Journal
Altern Ther Health Med. 2024 Jul;30(7):12-19. PMID: 39110045
Abstract

Background: Urinary tract infection (UTI) is a renal infection that affects the urinary tract and is global problem related to health and many people are affected each year at some points of their lives. Modern studies about urinary tract infections show that almost one third of the world's population has been suffering from this ailment. Different antibacterial medicines have been reported to have resistance against pathogens. In order to overcome the problem, exploration for new and dynamic antibacterial agents from natural sources is the emerging trend. 

Primary study objective: The primary objective was to evaluate the efficacy and safety of the polyherbal test drug formulation, "Crano-cure", as treatment for UTIs. 

Methods/design: In the current study, clinical trials were designed to evaluate the effects of the polyherbal formulation "Crano-cure" compared to the standard drug Ciprofloxacin in randomized, controlled multicenter trial of 205 patients, analyzing clinical outcomes and safety profiles. 

Setting and participants: Conducted across multiple centers, including Shifa-ul-Mulk Memorial Hospital at Hamdard University Karachi and three other clinics, the study involved 205 patients aged 15-60, irrespective of their socioeconomic status. 

Intervention: Patients were classified into two groups i.e. control group (ciprofloxacin) and the test group (crane-cure). Polyherbal formulation of 500 mg Crano-cure capsules two times in a day were administered to the test group for 28 days. The control group was administered a control ciprofloxacin tablet 500 mg two times in a day for 28 days. 

Primary outcome measures: The drug was found safe for further clinical study after observing changes or improvements in UTI symptoms, urine culture and blood complete tests. The clinical trial was dully registered on the US National Library of Medicine, ClinicalTrials.gov Identifier: NCT04575493. The trial was accompanied in the instructions of EC (Ethical Committee). The study plan and procedures were displayed to the BASR (Board of Advance Studies and Research) and board members of the Ethical Committee (EC), which was ERB-2021-9-1. 

Results: Clinical study results revealed the effectiveness of Crano-cure in the management of UTIs symptoms and hematological and biochemical parameters including blood complete test, liver function tests, renal function tests and lipid profile. Moreover, the test drug Crano-cure revealed a significance level (P ≤ .05) in compliance and cost-effectiveness compared to control ciprofloxacin.

The use of the combined drug Urolife-Next for recurrent lower urinary tract infections: clinical and microbiological aspects

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Authors
Slesarevskaya M N, Kuzmin I V, Kraeva L A, Smirnova E V, Lisitsa D A.
Journal
Urologiia. 2024 Jul;(3):39-49. Russian. PMID: 39563562.
Abstract

Background: Improving the efficiency of treatment and prevention of recurrent lower urinary tract infection (LUTI) is an important problem in modern urology. A significant role is given to the non-antibiotic measures. 

Aim: To evaluate the clinical and microbiological efficiency of the drug Urolife-Next in patients with recurrent UTI. 

Materials and methods: A total of 70 women with recurrent UTI aged 18 to 55 years (mean 35.1+/-10.1) and symptoms of cystitis were included in the study. After antibacterial therapy, all patients were divided into 3 groups. In the group 1 (n=24), patients took Urolife-Next 1 capsule 3 times a day for 90 days, in the group 2 (n=23) Urolife-Next in the same dose, but for a period of 30 days, while patients of group 3 (n=23) did not receive any treatment. The total follow-up period was 90 days. Frequency and severity of symptoms of recurrent UTI were assessed. The microbiological part of the study included evaluation of the presence and severity of anti-adhesive, anti-biofilm and direct antibacterial effects of the Urolife-Next against uropathogens isolated from urine of patients with exacerbation of UTI. 

Results: In group 1, in which patients took Urolife-Next throughout the study, the lowest frequency of relapses was seen. During the 90-day follow-up, recurrences of UTI occurred in only 3 (12.5%) patients in group 1, compared to 18 (78.3%) in group 3. In addition, in the group 1 there was a significantly lower severity of symptoms during exacerbation of cystitis compared to the initial episode, as well as to 3. Urolife-Next showed antibacterial activity against 29 (41.4%) of 70 strains of uropathogens. The minimum inhibitory concentration of Urolife-Next against gram-negative microorganisms was on average 2 times higher than for gram-positive pathogens. A pronounced anti-adhesive activity of Urolife-Next in vitro was also revealed. The maximum anti-adhesive effect was observed 2 hours after the start of the study. By this time, the adhesion index for cultures in the presence of Urolife-Next was 2.3 times lower than the control values for E. coli, 2.5 times for Kl. pneumoniae, and 2.9 times for E. faecalis. Significant antibiofilm activity of Urolife-Next was also noted. The severity of biofilm formation, which was assessed by changes in the optical density of cultures, decreased by 1.3-2.2 times, depending on the type of uropathogens. 

Conclusions: The results of the study prove the efficiency of the dietary supplement Urolife-Next for the prevention of recurrences in patients with UTI. Its components (D-mannose, cranberry extract, vitamins D and C, hyaluronic acid, probiotics) influence the main pathogenetic factors.