Editorial: Diet-microbe-host interactions in metabolic syndrome

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The Intricate Relationship between Diabetes, Diet and the Gut Microbiota

The most recent World Health Organization report revealed that the number of adults suffering from diabetes has almost quadrupled since 1980 to 422 million, thus drawing attention to the urgent need to step up prevention and treatment of this disease. This chronic ailment is often associated with serious complications such as increased risk of heart disease, stroke and kidney failure. In 2012 alone, diabetes lead to 1.5 million deaths. This dramatic rise is mainly due to the increased prevalence of type 2 diabetes and factors driving it include overweight and obesity. Novel studies in this area have advanced our understanding regarding the complex relationship between diet, gut microbiota and diabetes. Despite no clear microbiota signature is associated with diabetes, patients harbour a reduction of butyrate-producing species (Faecalibacterium prausnitzii, Roseburia intestinalis) as well as an increase in opportunistic pathogens. Furthermore, the functions of the gut microbiome (i.e., vitamin metabolism, transport of sugars, carbohydrate metabolism, short chain fatty acid (SCFA) synthesis, etc.) are also different in patients with type 2 diabetes, a fact that may significantly alter the course of disease. Diet is one of the most decisive factors that have an impact on the gut microbiome. Nutritional interventions using prebiotics (i.e., inulin-type fructans), polyphenols and arabinoxylans have been employed for the treatment of diabetes. Besides the shifts produced by these dietary components in the microbiome composition, it is worth mentioning their impact on host physiology through modulation of gut peptide production and glucose metabolism. The information presented within this chapter summarizes the most recent advances in the study of the microbiome-diet-diabetes interplay and analyses how these novel findings can be used in order to establish new therapeutic approaches for those with diabetes

Antibacterial Activity of New Dibenzoxepinone Oximes with Fluorine and Trifluoromethyl Group Substituents

In this paper we present the antimicrobial activity of some newly synthesized dibenz[b,e]oxepin derivatives bearing the oximino moiety, and fluorine (F) and trifluoromethyl (CF3) group substituents. The chemical structure and purity of the new compounds were assessed by using elemental analysis, NMR and FTIR spectroscopy. The new compounds were screened for their antibacterial activity towards Gram-positive and Gram-negative strains, by qualitative and quantitative assays. Our results demonstrated that the CF3 and F disubstituted compounds could be considered for the further development of novel antimicrobial drugs

Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation

IntroductionOne of the promising leads for the rapid discovery of alternative antimicrobial agents is to repurpose other drugs, such as nonsteroidal anti-inflammatory agents (NSAIDs) for fighting bacterial infections and antimicrobial resistance.MethodsA series of new carbazole derivatives based on the readily available anti-inflammatory drug carprofen has been obtained by nitration, halogenation and N-alkylation of carprofen and its esters. The structures of these carbazole compounds were assigned by NMR and IR spectroscopy. Regioselective electrophilic substitution by nitration and halogenation at the carbazole ring was assigned from H NMR spectra. The single crystal X-ray structures of two representative derivatives obtained by dibromination of carprofen, were also determined. The total antioxidant capacity (TAC) was measured using the DPPH method. The antimicrobial activity assay was performed using quantitative methods, allowing establishment of the minimal inhibitory/bactericidal/biofilm eradication concentrations (MIC/MBC/MBEC) on Gram-positive (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) strains. Computational assays have been performed to assess the drug- and lead-likeness, pharmacokinetics (ADME-Tox) and pharmacogenomics profiles.Results and discussionThe crystal X-ray structures of 3,8-dibromocarprofen and its methyl ester have revealed significant differences in their supramolecular assemblies. The most active antioxidant compound was 1i, bearing one chlorine and two bromine atoms, as well as the CO2Me group. Among the tested derivatives, 1h bearing one chlorine and two bromine atoms has exhibited the widest antibacterial spectrum and the most intensive inhibitory activity, especially against the Gram-positive strains, in planktonic and biofilm growth state. The compounds 1a (bearing one chlorine, one NO2 and one CO2Me group) and 1i (bearing one chlorine, two bromine atoms and a CO2Me group) exhibited the best antibiofilm activity in the case of the P. aeruginosa strain. Moreover, these compounds comply with the drug-likeness rules, have good oral bioavailability and are not carcinogenic or mutagenic. The results demonstrate that these new carbazole derivatives have a molecular profile which deserves to be explored further for the development of novel antibacterial and antibiofilm agents

Do wastewater treatment plants increase antibiotic resistant bacteria or genes in the environment? Protocol for a systematic review

Background: Antibiotic resistance is a global public health threat. Water from human activities is collected at wastewater treatment plants where processes often do not sufficiently neutralize antibiotic resistant bacteria and genes, which are further shed into the local environment. This protocol outlines the steps to conduct a systematic review based on the Population, Exposure, Comparator and Outcome (PECO) framework, aiming at answering the question "Are antimicrobial-resistant enterobacteriaceae and antimicrobial resistance genes present (O) in air and water samples (P) taken either near or downstream or downwind or down-gradient from wastewater treatment plants (E), as compared to air and water samples taken either further away or upstream or upwind or up-gradient from such wastewater treatment plant (C)?" Presence of antimicrobial-resistant bacteria and genes will be quantitatively measured by extracting their prevalence or concentration, depending on the reviewed study. Methods: We will search PubMed, EMBASE, the Cochrane database and Web of Science for original articles published from 1 Jan 2000 to 3 Sep 2018 with language restriction. Articles will undergo a relevance and a design screening process. Data from eligible articles will be extracted by two independent reviewers. Further, we will perform a risk of bias assessment using a decision matrix. We will synthesize and present results in narrative and tabular form and will perform a meta-analysis if heterogeneity of results allows it. Discussion: Antibiotic resistance in environmental samples around wastewater treatment plants may pose a risk of exposure to workers and nearby residents. Results from the systematic review outlined in this protocol will allow to estimate the extend of exposure, to inform policy making and help to design future studies

Natural Compounds for Wound Healing

Many plants or plant-derived compounds with high levels of antioxidants and anti-inflammatory, immunomodulatory, and antimicrobial properties could be of great benefit for wound healing. Several studies have documented the use of plant extracts for the development of bioactive wound dressings. The purpose of this chapter is to give an update about the vegetal and bee products, which can be used as bioactive substances in wound dressings or in other formulations for wound healing. The adverse effects of plant and bee extracts, such as contact allergies, are also presented. In order to better exploit the huge reservoir of pharmacologically active plant-derived compounds and extracts, standardized methodology and clinical trials are necessary to give more concrete evidence supporting the use of traditional medicine in wound management

Microbiota signatures in type-2 diabetic patients with chronic kidney disease - A Pilot Study

The human microbiota is paramount for normal host physiology. Altered host-microbiome interactions are part of the pathogenesis of numerous common ailments. Currently, much emphasis is placed on the involvement of the microbiome in the pathogenesis of type-2 diabetes mellitus (T2DM), impaired glucose tolerance, and other metabolic disorders (i.e. obesity). Several studies found highly significant correlations of specific intestinal bacteria with T2DM. A better understanding of the role of the microbiome in diabetes and its complications might provide new insights in the development of new therapeutic principles. Our pilot study investigates the microbiota patterns in Romanian type-2 diabetic patients with diabetic kidney disease. Fecal samples were collected from type 2-diabetic patients and healthy controls and further used for bacterial DNA isolation. Using 16 rDNA qRT-PCR, we analyzed phyla abundance (Bacteroidetes, Firmicutes) as well as the relative abundance of specific bacterial groups (Lactobacillus sp., Enterobacteriaceae, Ruminococus sp., Prevotella sp., Faecalibacterium sp., Clostridium coccoides, Clostridium leptum). Our study also investigates the diabetic fungal microbiome for the first time. Furthermore, we report significant correlations between the treatment regimen and microbiota composition in diabetic nephropathy