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The absorptive effects of orobuccal non-liposomal nano-sized glutathione on blood glutathione parameters in healthy individuals: A pilot study.
Bruggeman, BK, Storo, KE, Fair, HM, Wommack, AJ, Carriker, CR, Smoliga, JM
PloS one. 2019;(4):e0215815
Abstract
BACKGROUND Glutathione is an endogenous antioxidant found in oxidized (GSSG) and reduced (GSH) forms. Glutathione depletion is indicative of oxidative stress and occurs in various pathological conditions and following extreme exercise activity. Raising blood glutathione concentration has potential to attenuate and prevent chronic disease and also to improve recovery from exercise. There are a number of challenges to achieving this through traditional dietary supplements, and thus there is a need to develop optimized delivery methods to improve blood glutathione status. This study evaluated the effect of a novel glutathione formulation on blood glutathione parameters in healthy individuals. METHODS 15 (8 male) healthy individuals (25±5y old, 78.0±14.6kg) participated in a single-blinded randomized placebo-controlled crossover study, with a minimum one-week washout period between treatments. Participants were overnight fasted and administered 1mL of a non-liposomal nano-size glutathione solution (NLNG) containing 200mg of glutathione or 1mL of placebo lacking glutathione. The solution was held in the mouth for 90 seconds before the remainder was swallowed. Blood was collected at baseline, 5, 10, 30, 60 and 120 minutes post-treatment. Protein-bound plasma and erythrocyte lysate concentrations of GSH and GSSG were measured at all time points using previously validated procedures. Linear mixed effects models were used to compare differences between baseline and post-treatment glutathione concentrations between NLNG and placebo for each parameter. RESULTS There was a significant main effect for treatment type, such that increases in GSH concentration in erythrocyte lysate were greater following NLNG than placebo (p = 0.001). Similar significant main effects for treatment were also found for total (protein bound + erythrocyte lysate) GSH (p = 0.015) and GSSG (p = 0.037) concentration, as well as total blood glutathione pool (GSH+GSSG, p = 0.006). DISCUSSION NLNG increased multiple blood glutathione parameters compared to placebo. Future research should examine whether NLNG can attenuate oxidative stress.
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Metabolic Signaling and Spatial Interactions in the Oral Polymicrobial Community.
Miller, DP, Fitzsimonds, ZR, Lamont, RJ
Journal of dental research. 2019;(12):1308-1314
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Abstract
Oral supra- and subgingival biofilms are complex communities in which hundreds of bacteria, viruses, and fungi reside and interact. In these social environments, microbes compete and cooperate for resources, such as living space and nutrients. The metabolic activities of bacteria can transform their microenvironment and dynamically influence the fitness and growth of cohabitating organisms. Biofilm communities are temporally and spatially organized largely due to cell-to-cell communication, which promotes synergistic interactions. Metabolic interactions maintain biofilm homeostasis through mutualistic cross-feeding, metabolic syntrophy, and cross-respiration. These interactions include reciprocal metabolite exchanges that promote the growth of physiologically compatible bacteria, processive catabolism of complex substrates, and unidirectional interactions that are globally important for the polymicrobial community. Additionally, oral bacterial interactions can lead to detoxification of oxidative compounds, which will provide protection to the community at large. It has also been established that specific organisms provide terminal electron acceptors to partner species that result in a shift from fermentation to respiration, thus increasing ATP yields and improving fitness. Indeed, many interspecies relationships are multidimensional, and the net outcome can be spatially and temporally dependent. Cross-kingdom interactions also occur as oral yeast are antagonistic to some oral bacteria, while numerous mutualistic interactions contribute to yeast-bacterial colonization, fitness in the oral community, and the pathogenesis of caries. Consideration of this social environment reveals behaviors and phenotypes that are not apparent through the study of microbes in isolation. Here, we provide a comprehensive overview of the metabolic interactions that shape the oral microbial community.
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Lactobacillus brevis CD2 for Prevention of Oral Mucositis in Patients With Head and Neck Tumors: A Multicentric Randomized Study.
DE Sanctis, V, Belgioia, L, Cante, D, LA Porta, MR, Caspiani, O, Guarnaccia, R, Argenone, A, Muto, P, Musio, D, DE Felice, F, et al
Anticancer research. 2019;(4):1935-1942
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Abstract
BACKGROUND Oropharyngeal mucositis occurs in virtually all patients with head and neck cancer receiving radiochemotherapy. The manipulation of the oral cavity microbiota represents an intriguing and challenging target. PATIENTS AND METHODS A total of 75 patients were enrolled to receive Lactobacillus brevis CD2 lozenges or oral care regimen with sodium bicarbonate mouthwashes. The primary endpoint was the incidence of grade 3 or 4 oropharyngeal mucositis during radiotherapy treatment. RESULTS There was no statistical difference in the incidence of grade 3-4 oropharyngeal mucositis between the intervention and control groups (40.6% vs. 41.6% respectively, p=0.974). The incidence of pain, dysphagia, body weight loss and quality of life were not different between the experimental and standard arm. CONCLUSION Our study was not able to demonstrate the efficacy of L. brevis CD2 lozenges in preventing radiation-induced mucositis in patients with head and neck cancer. Although modulating homeostasis of the salivary microbiota in the oral cavity seems attractive, it clearly needs further study.
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Critical Appraisal of Oral Pre- and Probiotics for Caries Prevention and Care.
Zaura, E, Twetman, S
Caries research. 2019;(5):514-526
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Abstract
In recent years, the concept of preventing caries-related microbial dysbiosis by enhancing the growth and survival of health-associated oral microbiota has emerged. In this article, the current evidence for the role of oral pre- and probiotics in caries prevention and caries management is discussed. Prebiotics are defined as "substrates that are selectively utilized by host microorganisms conferring a health benefit." With regard to caries, this would include alkali-generating substances such as urea and arginine, which are metabolized by some oral bacteria, resulting in ammonia production and increase in pH. While there is no evidence that urea added to chewing gums or mouth rinses significantly contributes to caries inhibition, multiple studies have shown that arginine in consumer products can exert an inhibitory effect on the caries process. Probiotics are "live microorganisms which when administrated in adequate amounts confer a health benefit on the host." Clinical trials have suggested that school-based programs with milk supplemented with probiotics and probiotic lozenges can reduce caries development in preschool children and in schoolchildren with high caries risk. Due to issues with research ethics (prebiotics) and risk of bias (prebiotics, probiotics), the confidence in the effect estimate is however limited. Further long-term clinical studies are needed with orally derived probiotic candidates, including the health-economic perspectives. In particular, the development and evaluation of oral synbiotic products, containing both prebiotics and a probiotic, would be of interest in the future management of dental caries.
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The oral microbiome in oral lichen planus during a 1-year randomized clinical trial.
Kragelund, C, Keller, MK
Oral diseases. 2019;(1):327-338
Abstract
BACKGROUND Several recent studies have investigated the oral bacteriome in oral lichen planus (OLP), but longitudinal changes in microbiome have not been investigated. OBJECTIVE To study the bacteriome and mycobiome in OLP over a 1-year period and the impact of topical treatment. MATERIAL AND METHODS Samples from 22 symptomatic OLP patients from a double-blinded, randomized intervention study were collected over a 1-year course at five visits. Bacterial and fungal abundances were investigated through lesional cytobrush (CB) and full mouthwash (MW). Initially, all patients received conventional (antimycotic or steroid) and probiotic or placebo treatment. RESULTS The microbial composition differed between the MW and CB samples. During the study period, the microbial composition was individual, with pronounced variability between visits. Patients grouped according to initial conventional treatment. During the study period, unidirectional change in the bacteriome was seen in the antimycotic group, whereas the mycobiome was stable. Malassezia restricta was the most abundant fungus. CONCLUSIONS The microbial composition of MW and CB differs in OLP. CB composition is less influenced by conventional and probiotic intervention. Initial antimycotic treatment influenced the bacteriome during the 1-year period. How the oral microbiome in health and disease is influenced by individual variability of fungi and bacteria, and Malassezia needs further investigation.
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Relative homogeneity of oral bacterial oral in Crohn's disease compared to ulcerative colitis and its connections with antioxidant defense - preliminary report.
Szczeklik, K, Owczarek, D, Cibor, D, Cześnikiewicz-Guzik, M, Krzyściak, P, Krawczyk, A, Mach, T, Karczewska, E, Krzyściak, W
Folia medica Cracoviensia. 2019;(1):15-35
Abstract
INTRODUCTION Interactions between oral microbiota and systemic diseases have been suggested. We aimed to examine the composition of oral microbiota with reference to antioxidative defense and its correlation with clinical state in Crohn's disease (CD) in comparison to ulcerative colitis (UC). MATERIALS AND METHODS Smears were taken from the buccal and tongue mucosa of patients with CD, UC and controls, and cultured with classical microbiology methods. Bacterial colonies were identified using matrix-assisted laser desorption/ionization (MALDI) with a time-of-flight analyzer (TOF). Blood morphology and C-reactive protein (CRP) were analyzed in the hospital laboratory. Antioxidative defense potential (FRAP) was determined using spectrophotometry in saliva and serum. RESULTS Oral microbiota in CD patients were characterized by lower diversity in terms of the isolated bacteria species compared to UC and this correlated with reduced FRAP in the oral cavity and intensified systemic inflammation. Oral microbiota composition in CD did not depend on the applied treatment. In CD patients, a negative correlation was observed between the FRAP value in saliva and serum and the CRP value in serum. Individual differences in the composition of oral microbiota suggest that different bacteria species may be involved in the induction of oxidative stress associated with a weakening of antioxidative defense in the oral cavity, manifested by ongoing systemic inflammation. CONCLUSIONS Analysis of both the state of the microbiota and antioxidative defense of the oral cavity, as well as their referencing to systemic inflammation may potentially prove helpful in routine diagnostic applications and in aiding a better understanding of CD and UC pathogenesis associated with oral microbiota.
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INFOGEST static in vitro simulation of gastrointestinal food digestion.
Brodkorb, A, Egger, L, Alminger, M, Alvito, P, Assunção, R, Ballance, S, Bohn, T, Bourlieu-Lacanal, C, Boutrou, R, Carrière, F, et al
Nature protocols. 2019;(4):991-1014
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Abstract
Developing a mechanistic understanding of the impact of food structure and composition on human health has increasingly involved simulating digestion in the upper gastrointestinal tract. These simulations have used a wide range of different conditions that often have very little physiological relevance, and this impedes the meaningful comparison of results. The standardized protocol presented here is based on an international consensus developed by the COST INFOGEST network. The method is designed to be used with standard laboratory equipment and requires limited experience to encourage a wide range of researchers to adopt it. It is a static digestion method that uses constant ratios of meal to digestive fluids and a constant pH for each step of digestion. This makes the method simple to use but not suitable for simulating digestion kinetics. Using this method, food samples are subjected to sequential oral, gastric and intestinal digestion while parameters such as electrolytes, enzymes, bile, dilution, pH and time of digestion are based on available physiological data. This amended and improved digestion method (INFOGEST 2.0) avoids challenges associated with the original method, such as the inclusion of the oral phase and the use of gastric lipase. The method can be used to assess the endpoints resulting from digestion of foods by analyzing the digestion products (e.g., peptides/amino acids, fatty acids, simple sugars) and evaluating the release of micronutrients from the food matrix. The whole protocol can be completed in ~7 d, including ~5 d required for the determination of enzyme activities.
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Lollipop containing Glycyrrhiza uralensis extract reduces Streptococcus mutans colonization and maintains oral microbial diversity in Chinese preschool children.
Chen, Y, Agnello, M, Dinis, M, Chien, KC, Wang, J, Hu, W, Shi, W, He, X, Zou, J
PloS one. 2019;(8):e0221756
Abstract
The anticariogenic activity of the extract of Glycyrrhiza uralensis (licorice) has been well documented. We recently developed an herbal lollipop containing licorice extracts with Glycyrrhizol A, the compound displaying strong antimicrobial activity against Streptococcus mutans. Preliminary testing showed that the herbal lollipop reduced salivary S. mutans counts in vivo. In this study, we aimed to further test the efficacy of this herbal lollipop for reducing salivary S. mutans levels, and investigate its impact on salivary microbiome. Using a well-established in vitro oral microbiome model, we showed that licorice extract displays targeted killing against S. mutans without affecting the biodiversity of the community. In vivo study corroborated in vitro findings, showing for high caries-risk children aged 3-6 with salivary S. mutans levels >5x105 cells/ml, daily use of 2 licorice-containing lollipops for 3 weeks significantly reduced salivary S. mutans levels compared to the control group. Salivary microbiome analysis showed either no change or even increase in phylogenetic diversity of the oral community following herbal lollipop usage. Although further study with longer term observation is needed, these results suggest that use of licorice extract-containing lollipops can be as a simple and effective way to reduce the risk of dental caries in children.
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The Role of Exopolysaccharides in Oral Biofilms.
Cugini, C, Shanmugam, M, Landge, N, Ramasubbu, N
Journal of dental research. 2019;(7):739-745
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Abstract
The oral cavity contains a rich consortium of exopolysaccharide-producing microbes. These extracellular polysaccharides comprise a major component of the oral biofilm. Together with extracellular proteins, DNA, and lipids, they form the biofilm matrix, which contributes to bacterial colonization, biofilm formation and maintenance, and pathogenesis. While a number of oral microbes have been studied in detail with regard to biofilm formation and pathogenesis, the exopolysaccharides have been well characterized for only select organisms, namely Streptococcus mutans and Aggregatibacter actinomycetemcomitans. Studies on the exopolysaccharides of other oral organisms, however, are in their infancy. In this review, we present the current research on exopolysaccharides of oral microbes regarding their biosynthesis, regulation, contributions to biofilm formation and stability of the matrix, and immune evasion. In addition, insight into the role of exopolysaccharides in biofilms is highlighted through the evaluation of emerging techniques such as pH probing of biofilm colonies, solid-state nuclear magnetic resonance for macromolecular interactions within biofilms, and super-resolution microscopy analysis of biofilm development. Finally, exopolysaccharide as a potential nutrient source for species within a biofilm is discussed.
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Potential of chitosan-based carrier for periodontal drug delivery.
Sah, AK, Dewangan, M, Suresh, PK
Colloids and surfaces. B, Biointerfaces. 2019;:185-198
Abstract
Periodontal diseases are chronic infectious diseases and are a major oral health burden. With the progress in the understanding of etiology, epidemiology and pathogenesis of periodontal diseases coupled with the understanding of the polymicrobial synergy in the dysbiotic oral microbial flora, several new therapeutic targets have been identified. The strategies to curb bacterial growth and production of factors that gradually destroy the tissue surrounding and supporting the teeth have been the cornerstone for inhibiting periodontitis. Systemic administration of antibiotics for the treatment of periodontitis have shown several drawbacks including: inadequate antibiotic concentration at the site of the periodontal pocket, a rapid decline of the plasma antibiotic concentration to sub-therapeutic levels, the development of microbial resistance due to sub-therapeutic drug levels and peak-plasma antibiotic concentrations which may be associated with various side effects. These obvious disadvantages have evoked an interest in the development of localized drug delivery systems that can provide an effective concentration of antibiotic at the periodontal site for the duration of the treatment with minimal side effects. A targeted sustained release device which could be inserted in the periodontal pocket and prolong the therapeutic levels at the site of action at a much lower dose is the need of the hour. Chitosan, a deacetylated derivative of chitin has attracted considerable attention owing to its special properties including antimicrobial efficacy, biodegradability, biocompatibility and non-toxicity. It also has the propensity to act as hydrating agent and display tissue healing and osteoinducting effect. The aim of this review is to shine a spotlight on the chitosan based devices developed for drug delivery application in the effective treatment of various periodontal disorders. The chitosan based carriers like fibers, films, sponge, microparticles, nanoparticles, gels that have been designed for sustained release of drug into the periodontal pocket are highlighted.