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Do dietary interventions exert clinically important effects on the bioavailability of β-lactam antibiotics? A systematic review with meta-analyses

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Authors
Wiesner A, Zagrodzki P, Paśko P
Journal
J Antimicrob Chemother. 2024 Apr 2;79(4):722-757. doi: 10.1093/jac/dkae028. PMID: 38334389
Abstract

Background: Managing drug-food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics.

Methods: We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 β-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices.

Results: Eighteen of 25 β-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed β-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor).

Conclusions: Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.

Effect of Dietary Berry Supplementation on Antioxidant Biomarkers in Adults with Cardiometabolic Risks: A Systematic Review of Clinical Trials

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Authors
Helm MM, Alaba T, Klimis-Zacas D, Izuora K, Basu A
Journal
Antioxidants (Basel). 2023 May 30;12(6):1182. doi: 10.3390/antiox12061182. PMID: 37371912; PMCID: PMC10295504
Abstract

Cardiometabolic conditions are closely associated with inflammation and oxidative stress. Dietary berries may serve as a beneficial nutrition intervention to address the features of cardiometabolic dysfunction and associated oxidative stress. The high antioxidant status of dietary berries may increase antioxidant capacity and reduce biomarkers of oxidative stress. This systematic review was conducted to investigate these effects of dietary berries. The search was conducted using PubMed, Cochrane Library, Web of Science, and citation searching. Through this search we identified 6309 articles and 54 were included in the review. Each study’s risk of bias was assessed using the 2019 Cochrane Methods’ Risk of Bias 2 tool. Antioxidant and oxidative stress outcomes were evaluated, and the magnitude of effect was calculated using Cohen’s d. A range of effectiveness was reported in the included studies and the quality of the studies differed between the parallel and crossover trials. Considering the inconsistency in reported effectiveness, future investigations are warranted to determine the acute and sustained reductions of oxidative stress biomarkers from dietary berry intake.

Effect of polyphenol compounds on Helicobacter pylori eradication: a systematic review with meta-analysis

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Authors
Wang Q, Yao C, Li Y, Luo L, Xie F, Xiong Q, Feng P
Journal
BMJ Open. 2023 Jan 5;13(1):e062932. doi: 10.1136/bmjopen-2022-062932. PMID: 36604137; PMCID: PMC9827256
Abstract

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.

Effects of Anthocyanin-rich Berries on the Risk of Metabolic Syndrome: A Systematic Review and Meta-analysis

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Authors
Wilken MR, Lambert MNT, Christensen CB, Jeppesen PB
Journal
Rev Diabet Stud. 2022 Mar 9;18(1):42-57. doi: 10.1900/RDS.2022.18.42. PMID: 35300756; PMCID: PMC9382680
Abstract

Metabolic syndrome (MetS) can lead to fatal complications, including cardiovascular disease. Emerging evidence suggests has emerged that increased fruit and vegetable intake and decreased intake of saturated fats, simple sugars, and processed foods can improve cardiovascular health. Anthocyanins (color pigments) have anti-inflammatory and antioxidant capacities but are of low bioavailability. In this systematic review and meta-analysis, we investigate the possible beneficial effects of the intake of berries high in anthocyanins on MetS risk factors. We also investigate the influences of high-density lipoprotein (HDL), low- density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC).

Neuroprotective Effects of Cranberry Juice Treatment in a Rat Model of Parkinson's Disease

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Authors
Witucki Ł, Kurpik M, Jakubowski H, Szulc M, Łukasz Mikołajczak P, Jodynis-Liebert J, Kujawska M
Journal
Nutrients. 2022 May 11;14(10):2014. doi: 10.3390/nu14102014. PMID: 35631155; PMCID: PMC9144186
Abstract

Rich in polyphenols, cranberry juice (CJ) with high antioxidant activity is believed to contribute to various health benefits. However, our knowledge of the neuroprotective potential of cranberries is limited. Previously, we have demonstrated that CJ treatment controls oxidative stress in several organs, with the most evident effect in the brain. In this study, we examined the capability of CJ for protection against Parkinson’s disease (PD) in a rotenone (ROT) rat model. Wistar rats were administered with CJ in a dose of 500 mg/kg b.w./day (i.g.) and subcutaneously injected with ROT (1.3 mg/kg b.w./day). The experiment lasted 45 days, including 10 days pre-treatment with CJ and 35 days combined treatment with CJ and ROT. We quantified the expression of α-synuclein and apoptosis markers in the midbrain, performed microscopic examination, and assessed postural instability to evaluate the CJ neuroprotective effect. Our results indicate that the juice treatment provided neuroprotection, as evidenced by declined α-synuclein accumulation, Bax and cleaved/active caspase-9 expression, and normalized cytochrome c level that was accompanied by the enhancement of neuronal activity survival and improved postural instability. Importantly, we also found that long-term administration of CJ alone in a relatively high dose may exert a deleterious effect on cell survival in the midbrain. 

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

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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.