Lactobacillus rhamnosus induces CYP3A and changes the pharmacokinetics of verapamil in rats.

Verapamil, a calcium channel blocker, has been approved as the first-line drug for treatment of angina pectoris, hypertension and supraventricular tachycardia. Lactobacillus rhamnosus, one of the normal strains in human intestinal tract, is very popular in the probiotic market for conferring a health benefit on the host. This report investigated the potential of gut microbiota-drug interactions between lactobacillus rhamnosus and verapamil via using wild type (WT) and Cyp3a1/2 knockout (KO) rats. In WT rats, administration of Lactobacillus rhamnosus for 14 days decreased systemic exposure of verapamil and increased its metabolite norverapamil in vivo, and resulted in gut microbiota-drug interactions. In Cyp3a1/2 KO rats, however, this interaction disappeared. Further studies found that Lactobacillus rhamnosus induced CYP3A activity and expression, and changed the composition of gut microbiota, thus changing the pharmacokinetics of verapamil. These results demonstrated the interaction between lactobacillus rhamnosus and verapamil, and indicated that the effect of gut microbiota on metabolic enzymes cannot be ignored.

The efficacy and toxicity of antineoplastic antimetabolites: Role of gut microbiota.

The incidence and mortality of cancer are rapidly growing all over the world. Nowadays, antineoplastic antimetabolites still play a key role in the chemotherapy of cancer. However, the interindividual variations in the efficacy and toxicity of antineoplastic antimetabolites are nonnegligible challenges to their clinical applications. Although many studies have focused on genetic variation, the reasons for these interindividual variations have still not been fully understood. Gut microbiota is reported to be associated with the efficacy and toxicity of antineoplastic antimetabolites. In this review, we summarize the interaction of antineoplastic antimetabolites on gut microbiota and the influences of shifted gut microbiota profiles on the efficacy and toxicity of antineoplastic antimetabolites. The factors affecting the efficacy and toxicity of antineoplastic antimetabolites via gut microbiota are also discussed. In addition, we present our viewpoints that regulating the gut microbiota may increase the efficacy and decrease the toxicity of antineoplastic antimetabolites. This will help us better understand the new mechanism via gut microbiota and promote individualized use of antineoplastic antimetabolites.

Potential bioaccessibility of phenolic acids in whole wheat products during in vitro gastrointestinal digestion and probiotic fermentation.

Health benefits of whole wheat products are partially attributed by their unique phenolic compounds. This study investigated effect of simulated gastrointestinal digestion and probiotic fermentation on releasing of phenolic acids from whole wheat foods (bread, cookie, and pasta). Kinetics results showed that more phenolic acids were released within the first hour of gastric and intestinal digestions compared to the prolonged digestion. Lactobacillus rhamnosus GG, a common probiotic strain, released additional phenolic acids from the digestive residues during fermentation. Simulated digestion released more soluble trans-ferulic acid than chemical extraction in breads (17.69 to 102.71 µg/g), cookie (15.81 to 54.43 µg/g), and pasta (4.88 to 28.39 µg/g). Phenolic acid composition of whole wheat products appeared to be better estimated by digestion methods than the chemical extraction method. The unique insoluble-bound nature and fermentability of wheat phenolic acids may lead to a mechanistic understanding of whole grain consumption for potential colorectal cancer prevention.

Exogenous enzymes and probiotics alter digestion kinetics, volatile fatty acid content and microbial interactions in the gut of Nile tilapia.

Sustainable aquafeed production requires fishmeal replacement, leading to an increasing use of plant-derived ingredients. As a consequence, higher levels of antinutritional substances, such as non-starch polysaccharides and phytate, are present in aquafeeds, with negative effects on fish performance, nutrient digestibility and overall gut health. To alleviate these negative effects, providing exogenous digestive enzymes and/or probiotics can be an effective solution. In this study, we tested the effect of dietary supplementation of enzymes (phytase and xylanase) and probiotics (three strains of Bacillus amyloliquefaciens) on nutrient digestion kinetics and volatile fatty acid content along the gut, and the distal gut microbiome diversity in Nile tilapia. Chyme volatile fatty content was increased with probiotic supplementation in the proximal gut, while lactate content, measured for the first time in vivo in fish, decreased with enzymes along the gut. Enzyme supplementation enhanced crude protein, Ca and P digestibility in proximal and middle gut. Enzymes and probiotics supplementation enhanced microbial interactions as shown by network analysis, while increased the abundance of lactic acid bacteria and Bacillus species. Such results suggest that supplementation with exogenous enzymes and probiotics increases nutrient availability, while at the same time benefits gut health and contributes to a more stable microbiome environment.

Kinetics of Intestinal Presence of Spores Following Oral Administration of Bacillus clausii Formulations: Three Single-Centre, Crossover, Randomised, Open-Label Studies.

BACKGROUND AND OBJECTIVE: Probiotics are live microorganisms that may provide benefits including the prevention of gastrointestinal disorders and other diseases. Enterogermina is a probiotic mix of spores from four strains of Bacillus clausii (O/C, T, N/R and SIN), available in several oral formulations. The objective of this analysis was to evaluate and compare the kinetic profiles of different formulations of Enterogermina-vial [E4 once daily (OD) and E2 twice daily (BID)], capsule [EC2 three times daily (TID)], oral powder for suspension (ES6 OD) and oral powder not requiring suspension (E6 OD) from two studies from 2012 (EUDRACT 2010-024497-19 and 2010-023187-41) and one study from 2016 (EUDRACT 2015-003330-27). METHODS: B. clausii spores were counted in homogenised faecal samples (results expressed as counts per gram) or after culture at 37 °C for 24-36 h (results expressed as colony-forming units). Kinetics were assessed by area under the concentration-time curve (AUC), maximum concentration (Cmax), time to maximum concentration (Tmax) and spore presence/persistence. RESULTS: In total, 22 subjects in each of the 2012 studies and 30 subjects in the 2016 study were randomised (mean age 25.0-33.8 years across studies). The mean (±SD) absolute faecal spore counts (in millions) expressed as AUC per hour were 270.7 ± 147.7 (E2 BID) and 213.8 ± 60.2 (E4 OD) in 2012 EGKINETIC4, 312.7 ± 218.0 (EC2 TID) and 319.0 ± 221.1 (ES6 OD) in 2012 EGKINETIC6, and 212.6 ± 118.0 (E6 OD) and 293.2 ± 247.2 (ES6 OD) in 2016 EGKINETIC6OP. The kinetic profiles of the different formulations of Enterogermina were similar, with superimposable AUC and daily curve profiles in each study up to the 8th day post dose. B. clausii spore presence/persistence in the intestine of healthy volunteers did not differ between the two formulations within each of the three studies. Enterogermina was well tolerated across all formulations and studies. CONCLUSION: These results show different formulations of Enterogermina had similar kinetic profiles within each study; however, they also showed that probiotics could be associated with high variability. The European Medicines Agency guidelines are the current bioequivalence reference, although only the Tmax parameter is used for high variability drugs. Due to the specific kinetics of probiotics, new parameters of bioequivalence could be necessary, considering, for example, variability via a parameter such as AUC. TRIAL REGISTRATION: EUDRACT 2010-024497-19, 2010-023187-41 and 2015-003330-27.

A quantitative model for metabolic intervention using gut microbes.

As medicine shifts toward precision-based and personalized therapeutics, utilizing more complex biomolecules to treat increasingly difficult and rare conditions, microorganisms provide an avenue for realizing the production and processing necessary for novel drug pipelines. More so, probiotic microbes can be co-opted to deliver therapeutics by oral administration as living drugs, able to survive and safely transit the digestive tract. As living therapeutics are in their nascency, traditional pharmacokinetic-pharmacodynamic (PK-PD) models for evaluating drug candidates are not appropriate for this novel platform. Using a living therapeutic in late-stage clinical development for phenylketonuria (PKU) as a case study, we adapt traditional oral drug delivery models to properly evaluate and inform the engineering of living therapeutics. We develop the adapted for living therapeutics compartmental absorption and transit (ALT-CAT) model to provide metrics for drug efficacy across nine age groups of PKU patients and evaluate model parameters that are influenced by patient physiology, microbe selection and therapeutic production, and dosing formulations. In particular, the ALT-CAT model describes the mathematical framework to model the behavior of orally delivered engineered bacteria that act as living therapeutics by adapting similar methods that have been developed and widely-used for small molecular drug delivery and absorption.

Development of chitosan-coated agar-gelatin particles for probiotic delivery and targeted release in the gastrointestinal tract.

This study reports the development of a novel and simple formulation for probiotic delivery using chitosan-coated agar-gelatin gel particles. This methodology involves the production of agar-gelatin particles by thermally treating a mixture of agar and gelatin solutions at high temperatures (121 °C) and subsequently coating with chitosan. The particles were able to protect the probiotic strain Lactobacillus plantarum NCIMB 8826 during incubation for 2 h in simulated gastric fluid (pH 2), as no statistically significant loss (P > 0.05) in cell concentration was observed, and also resist dissolution in simulated intestinal fluid (pH 7.2). Interestingly, this protection is related to the fact that the intense thermal treatment affected the physicochemical properties of agars and resulted in the formation of a strong and tight polymer network, as indicated by the X-ray diffraction (XRD) analysis. Using an in vitro faecal batch fermentation model simulating the conditions of the distal part of the large intestine (pH 6.7-6.9), it was demonstrated by quantitative real-time PCR that the majority of L. plantarum cells were released from the agar-gelatin particles within 30 to 48 h. Overall, this work led to the development of a novel methodology for the production of probiotic-containing particles, which is simpler compared with current encapsulation technologies and has a lot of potential to be used for the controlled release of probiotics and potentially other solid bioactives in the large intestine.Key Points• Chitosan gel particles is a simple and scalable method of probiotic encapsulation.• Autoclaving agar-gelatin particles increases their stability at low pH.• Chitosan gel particles protected L. plantarum during gastrointestinal conditions.• Probiotics could be controlled release in the colon using chitosan gel particles.

A novel route for double-layered encapsulation of probiotics with improved viability under adverse conditions.

To improve the survivability of probiotics under the harsh conditions, a novel double-layered vehicle, which was developed by a one-step coaxial electrospinning procedure, was here used to encapsulate the probiotics. The morphology characterization analysis revealed that the electrospun fiber had a beaded morphology and core-shell structure. Probiotic cells were successfully encapsulated in the fibers (107 CFU/mg) and exhibited an oriented distribution along the fiber. Additionally, the encapsulation of core-shell fiber mat enhanced the tolerance of probiotic cells to simulated gastrointestinal conditions and no significant loss of viability was found (p > 0.05). Besides that, the encapsulated cells exhibited better thermal stability under heat moisture treatment, lower loss of viability (0.32 log CFU/mL) was occurred when compared with the free cells or encapsulated cells in uniaxial fiber mat. In conclusion, this double-layered vehicle presents a great potential in probiotic encapsulation and improving their resistant ability to the harsh conditions.

Spray dried formulation of mesalamine embedded with probiotic biomass for the treatment of ulcerative colitis: in-vitro and in-vivo studies.

This study is using the targeted approach and anti-inflammatory action of the probiotic biomass to lessen the side effects of therapeutic agents of ulcerative colitis. The aim of the present study is to prepare mesalamine loaded eudragit S-100 with probiotic microparticles by spray drying method. The in-vitro release of the optimized formulation was 90.55 ± 2.42 in 24 hr, which display controlled drug release of mesalamine at a particular region. Mesalamine loaded eudragit S-100 with probiotic microparticles (F12) presented average particle size of 4.91 µm. The statistical analysis was done by one way ANOVA and then comparison test of Bonferroni was done and p values <.05 were considered as significant. The effects of spray dried microparticles over inflamed Caco-2 cell were also evaluated by determining the concentration of IL-8. From in-vivo study it was seen that pretreatment of mesalamine with probiotic prevents DNBS (Dinitrobenzenesulfonic acid) induced colitis in rats and represents protective action against ulcerative colitis because of its antioxidant and anti-inflammatory actions. The results give the foundation for a combination of targeted approach along with the anti-inflammatory potential of the probiotic which might help to decrease the problems which are seen with the traditional cure and management of ulcerative colitis.

Ultra-fast disintegrating ODTs comprising viable probiotic bacteria and HPMC as a mucoadhesive.

Orodispersible tablets (ODTs) are a convenient dosage form and a recent trend in formulation development. The fast disintegration is accompanied by rapid removal of the active principle and the excipients from the mouth due to saliva flow and swallowing. Probiotic bacteria are a promising strategy to fight disease with bacterial aetiology in the mouth, but a certain residence time in the oral cavity is inevitable to exert their positive effects. The addition of a mucoadhesive polymer, like hydroxypropyl methylcellulose (HPMC), is an auspicious strategy to prolong this residence time. Nevertheless, the disintegration time of the tablets should still meet the acceptance level from the FDA (<30 s). To reach intimate contact of bacteria and mucoadhesive polymer on the one hand and to support fast disintegration on the other hand, granulation of probiotic bacteria and mucoadhesive HPMC with a methacrylic acid copolymer was performed first. Moreover, high mucoadhesion could be obtained because bacteria and mucoadhesive polymer could interact more strongly with the mucosa after the ODT disintegrated and the methacrylic acid copolymer dissolved in the pH neutral saliva.

Enhanced viability of layer-by-layer encapsulated Lactobacillus pentosus using chitosan and sodium phytate.

Lactobacillus pentosus (LP) are widely used as probiotics in food products, dietary supplements, and nutraceuticals due to their health-promoting effects. To confer a functional effect, the probiotics need to survive during shelf-life and transit through the high acidic conditions of the stomach and bile salts in the small intestine. Herein, LP was firstly encapsulated in a layer-by-layer approach using chitosan (CS) and sodium phytate (SP). After digestion in simulated gastrointestinal fluid (SGF) for 120 min and 4% bile salts for 3 h, plain-LP exhibited a 7.40 and 6.09 colony forming units/ml (cfu/ml) reduction. Interestingly, two layer coated LP ((CS/SP)2-LP) exhibited less death, which reduced 4.34 and 2.33 log cfu/ml, respectively. Specially, (CS/SP)2-LP also showed a higher survival rate compared to plain-LP in heat treatment experiments, especially 65 °C. In conclusion, layer-by-layer encapsulation of LP has great potential for the protection and delivery of probiotics in food and nutraceutical products.

Oral Delivery of Probiotics Using pH-Sensitive Phthalyl Inulin Tablets.

Probiotics show low cell viability after oral administration because they have difficulty surviving in the stomach due to low pH and enzymes. For the oral delivery of probiotics, developing a formula that protects the probiotic bacteria from gastric acidity while providing living cells is mandatory. In this study, we developed tablets using a new pH-sensitive phthalyl inulin (PI) to protect probiotics from gastric conditions and investigated the effects of different compression forces on cell survival. We made three different tablets under different compression forces and measured survivability, disintegration time, and kinetics in simulated gastric-intestinal fluid. During tableting, there were no significant differences in probiotic viability among the different compression forces although disintegration time was affected by the compression force. A higher compression force resulted in higher viability in simulated gastric fluid. The swelling degree of the PI tablets in simulated intestinal fluid was higher than that of the tablets in simulated gastric fluid due to the pH sensitivity of the PI. The probiotic viability formulated in the tablets was also higher in acidic gastric conditions than that for probiotics in solution. Rapid release of the probiotics from the tablet occurred in the simulated intestinal fluid due to the pH sensitivity. After 6 months of refrigeration, the viability of the PI probiotics was kept. Overall, this is the first study to show the pH-sensitive properties of PI and one that may be useful for oral delivery of the probiotics.

The Epithelial Barrier Model Shows That the Properties of VSL#3 Depend from Where it is Manufactured.

BACKGROUND: VSL#3 has been extensively investigated and is currently recommended for the prevention and treatment of chronic pouchitis and ulcerative colitis. Nonetheless, in vitro and in vivo studies have recently shown variability in the VSL#3 efficacy often attributed to the manufacturing process. OBJECTIVE: The aim was to comparatively study the in vitro effects of two VSL#3 preparations produced in different sites (named US- and Italy-made VSL#3) on CaCo-2 epithelial barrier model in terms of trans-epithelial electrical resistance (TEER), dextran flux and expression of Tight Junctions (TJ) proteins i.e. zonulin-1 (ZO-1) and occludin, in the absence or presence of a heat stress-related damage of monolayer. METHODS: TEER was evaluated on CaCo-2 differentiated monolayers. Epithelial permeability of polarized monolayers was assessed by measuring the FITC-labeled dextran flux from the apical to basolateral chambers. ZO-1/occludin levels were analyzed by western blot analysis. A set of experiments was performed to compare the effects of both VSL#3 on TEER values, dextran flux and ZO-1/occludin expression in CaCo-2 monolayers after heat stress exposure. RESULTS: US- and Italy-made VSL#3 have opposing effects on TEER values, dextran flux, and ZO- 1/occludin expression, being all these parameters negatively influenced just by Italy-made product. US-made probiotic did not affect baseline TEER, dextran flux and ZO-1 expression and strongly increased occludin levels. Of note, pre-treatment of monolayer with US-made VSL#3, but not Italy-made product, totally prevented the heat-induced epithelial barrier integrity loss. CONCLUSION: Our data trigger the need for reassessing efficacy or safety of the Italy-made VSL#3 considering intestinal epithelial barrier plays an important role in maintaining host health.

In vitro probiotic properties of vaginal Lactobacillus fermentum MG901 and Lactobacillus plantarum MG989 against Candida albicans.

Candida albicans is the most important Candida species causing vulvovaginal candidiasis (VVC). We investigated the potential of the probiotic strains Lactobacillus fermentum MG901 and L. plantarum MG989 towards control of C. albiacns. Cell viability tests following co-culturing with lactobacilli revealed that C. albicans cells lost metabolic activity and were eventually killed. Further studies revealed that MG901 and MG989 had high surface hydrophobicity that enhanced its adhesion ability to epithelial cell. The MG901 and MG989 showed coaggregation with E. coli and C. albicans to affect their adhesion and colonization. The adhesion of MG901 and MG989 to HT-29 cell and its inhibition of E. coli and C. albicans adherence to these cells were demonstrated. These incidences provided evidence of the possible colonization of MG901 and MG989 that would prevent binding and growth of E. coli and C. albicans onto intestinal epithelial cells. Following daily administration of 108 CFU of viable MG901 and MG989 orally, the animals' feces were examined for bacterial excretion. The potential probiotic MG901 and MG989 were found to persist for up to 6 days in the feces of mice. In conclusion, L. fermentum MG901 and L. plantarum MG989 have the potential to inhibit the yeast growth, which could possibly have played an important role in helping to clear VVC in vivo.

Bacteria-Carried Iron Oxide Nanoparticles for Treatment of Anemia.

The efficiency of maghemite nanoparticles for the treatment of anemia was sensibly higher when nanoparticles were incorporated onto the probiotic bacterium Lactobacillus fermentum (MNP-bacteria) than when administrated as uncoated nanoparticles (MNP). Plasma iron and hemoglobin, intestine expression of divalent metal transporter 1 (DMT1) and duodenal Cytochrome b (DcytB), as well as hepatic expression of the hormone hepcidin were fully restored to healthy levels after administration of MNP-bacteria but not of MNP. A magnetic study on biodistribution and biodegradation showed accumulation of maghemite nanoparticles in intestine lumen when MNP-bacteria were administrated. In contrast, MNP barely reached intestine. In vivo MRI studies suggested the internalization of MNP-bacteria into enterocytes, which did not occur with MNP. Transmission electronic microscopy confirmed this internalization. The collective analysis of results point out that L. fermentum is an excellent carrier to overcome the stomach medium and drive maghemite nanoparticles to intestine, where iron absorption occurs. Due the probiotic ability to adhere to the gut wall, MNP-bacteria internalize into the enterocyte, where maghemite nanoparticles are delivered, providing an adequate iron level into enterocyte. This paper advances a new route for effective iron absorption in the treatment of anemia.

In-vitro and In-vivo Pharmacokinetic Evaluation of Guar Gum-Eudragit® S100 Based Colon-targeted Spheroids of Sulfasalazine Co-administered with Probiotics.

BACKGROUND: Polysaccharide based delivery systems have been successfully used to target drugs to colon. In some recent reports, the superiority of concomitant administration of probiotics with such systems has been established. However, the pharmacokinetics of such symbiotic therapy remain unexplored hitherto. METHODS: This study deciphers the pharmacokinetic parameters of guar gum based colon targeted spheroids of sulfasalazine with co-administration of probiotics in experimental rats. Thirty rats were divided into five groups using Latin square design. These were subjected to treatment with delayed release formulation, uncoated spheroids, coated spheroid and coated spheroids along with probiotics. RESULTS: In case of delayed release formulation, negligible presence of sulfasalazine in plasma was observed in first 2h, followed by significant increase in sulfasalazine concentration after 3h. Higher plasma concentrations of sulfasalazine were detected for uncoated spheroids with and without probiotics. Negligible release of drug upto 5h and delayed Tmax in case of guar-gum coated sulfasalazine spheroids with or without probiotics clearly indicated successful formulation of colon targeted spheroids. Further, for coated spheroids (both with and without probiotics), the value of Tmax is found to be significantly higher than those with the other treatments. CONCLUSION: Colon targeted spheroids were therefore, found to reduce absorption of drug which, in turn, is expected to reduce the side effects as only local action in colon is required for treatment of colitis. This is the first report on pharmacokinetic study of a colon targeted delivery system co-administered with probiotics.

Evaluación del efecto de un estabilizador del microbioma vaginal sobre los resultados maternos y neonatales en mujeres con rotura prematura de membranas pretérmino / Evaluation of the effect of a vaginal microbiome stabilizer on maternal and neonatal outcomes in women with premature rupture of preterm membranes

Objetivo: evaluar, en mujeres con rotura prematura de membranas pretérmino, si un estabilizador del microbioma vaginal disminuye el riesgo de corioamnionitis clínica, aumenta la latencia al parto y reduce la morbimortalidad materna y neonatal. Sujetos y métodos: estudio de cohortes retrospectivo. Entre 2011-2014 se trató con Geliofil® vaginal a mujeres con rotura prematura de membranas entre las 24,0-29,6 semanas que estaban bajo antibioterapia de amplio espectro. Se compararon los resultados maternos y neonatales con un grupo histórico de características similares (2008-2011). Resultados: veinticinco mujeres fueron tratadas con Geliofil® y veinticuatro pertenecieron al grupo no tratado. El porcentaje de corioamnionitis clínica (32% vs. 33,3%), la edad gestacional al parto (media (desviación estándar)-30,3 (3,4) vs. 30,3 (3,1) semanas) y la latencia al parto (4,4 (5,1) vs. 4,3 (4,1) semanas) fueron similares en ambos grupos. No hubo diferencias en la morbimortalidad materna ni neonatal. Conclusión: el uso de Geliofil® no mejoró los resultados maternos ni neonatales en mujeres con rotura prematura de membranas Pretérmino (AU)

Objective: To evaluate if a vaginal ecosystem stabilizer, Geliofil®, administered to women with preterm prelabour rupture of membranes decreases the occurrence of clinical chorioamnionitis, increases latency to delivery and decreases maternal and neonatal morbimortality. Subjects and methods: Retrospective cohort study. From 2011-2014, vaginal Geliofil® was added to broad-spectrum antibiotic therapy of singleton pregnancies with diagnosis of preterm prelabour rupture of membranes between 24.0 and 29.6 weeks. Maternal and neonatal outcomes were compared with a historical group with similar characteristics (2008-2011). Results: Twenty-five women were treated with Geliofil® and 24 were included in the historic group. No differences were observed between groups in relation to gestational age at delivery (mean (standard deviation)-30.3 (3.4) vs. 30.3 (3.1) weeks), latency to delivery (4.4 (5.1) vs. 4.3 (4.1) weeks) or the occurrence of clinical chorioamnionitis (32% vs. 33.3%), respectively. Moreover, no differences were found in other maternal or neonatal outcomes evaluated. Conclusion: Geliofil®, as a vaginal ecosystem stabilizer, does not improve maternal or neonatal morbimortality in women with preterm prelabour rupture of membranes (AU)

Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.

Probiotics and oral health: A systematic review

BACKGROUND: Probiotics are microorganisms, mainly bacteria, which benefit the host's health. Many studies support the role of probiotics as a contributor to gastrointestinal health, and nowadays many authors are trying to prove its influence in oral health maintenance. OBJECTIVES: To review the published literature with the purpose of knowing the importance of using probiotics as a preventive and therapeutic method for oral infectious diseases management. MATERIAL AND METHODS: An electronic search in PubMed database with the keywords 'oral health AND probiotics AND dentistry' was conducted. The inclusion criteria were: randomized clinical trials (RCTs) that assess the action of any probiotic strain in the treatment and / or prevention of an infectious oral disease, RCTs that assess the action of any probiotic strain on counting colony forming units (CFU) of oral pathogens, systematic reviews and meta-analysis. The Jadad scale was used to assess the high quality of RCTs. RESULTS: Fifteen articles were considered for this review. Of which, 12 were RCTs of good / high quality (Jadad scale), two meta-analysis and one systematic review. CONCLUSIONS: The literature reviewed suggests probiotics usage could be beneficial for the maintenance of oral health, due to its ability to decrease the colony forming units (CFU) counts of the oral pathogens. However, randomized clinical trials with long-term follow-up periods are needed to confirm their efficacy in reducing the prevalence/incidence of oral infectious diseases. Furthermore, the recognition of specific strains with probiotic activity for each infectious oral disease is required, in order to determine exact dose, treatment time and ideal vehicles