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Helicobacter pylori (H. pylori) is known to colonize gastric mucosa, induce inflammation, and alter gastric microbiota resulting in a spectrum of gastric diseases. Likewise, changes in gut microbiota have recently been linked with various metabolic and inflammatory diseases. While extensive number of studies were published examining the relationship between H. pylori and gastric microbiota, little is known about the impact of H. pylori on downstream gut microbiota. In this study, we performed 16 S rRNA and ITS2-based microbial profiling analysis of 60 stool samples from adult individuals. Remarkably, the gut microbiota of H. pylori infected individuals was shown to be increased of members belonging to Succinivibrio, Coriobacteriaceae, Enterococcaceae, and Rikenellaceae. Moreover, gut microbiota of H. pylori infected individuals was shown to have increased abundance of Candida glabrata and other unclassified Fungi. These results links possible role for H. pylori-associated changes in the gut microbiota in intestinal mucosal barrier disruption and early stage colorectal carcinoma deployment. Altogether, the identified differences in bacterial and fungal composition provides important information that may eventually lead to the development of novel biomarkers and more effective management strategies.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with a high prevalence worldwide, especially among overweight and obese populations. T2DM is multifactorial with several genetic and acquired risk factors that lead to insulin resistance. Mounting evidence indicates that alteration of gut microbiome composition contribute to insulin resistance and inflammation. However, the precise link between T2DM and gut microbiome role and composition remains unknown. We evaluated the metabolic capabilities of the gut microbiome of twelve T2DM and six healthy individuals through shotgun metagenomics using MiSeq platform. We identified no significant differences in the overall taxonomic composition between healthy and T2DM subjects when controlling for differences in diet. However, results showed that T2DM enriched in metabolic pathways involved in menaquinone (vitamin K2) superpathway biosynthesis (PWY-5838) as compared to healthy individuals. Covariance analysis between the bacterial genera and metabolic pathways displaying difference in abundance (analysis of variance P<0.05) in T2DM as compared to healthy subjects revealed that genera belonging Firmicutes, Actinobacteria, and Bacteroidetes phyla contribute significantly to vitamin K2 biosynthesis. Further, the microbiome corresponding to T2DM with high glycosylated hemoglobin (HbA1c) (>6.5%) exhibit high abundance of genes involved in lysine biosynthesis and low abundance of genes involved in creatinine degradation as compared to T2DM with lower HbA1c (<6.5%). The identified differences in metabolic capabilities provide important information that may eventually lead to the development of novel biomarkers and more effective management strategies to treat T2DM.

The gut microbiome plays a significant role in the development of Type 2 Diabetes Mellitus (T2DM), but the functional mechanisms behind this association merit deeper investigation. Here, we used the nanopore sequencing technology for metagenomic analyses to compare the gut microbiome of individuals with T2DM from the United Arab Emirates (n = 40) with that of control (n = 44). DMM enterotyping of the cohort resulted concordantly with previous results, in three dominant groups Bacteroides (K1), Firmicutes (K2), and Prevotella (K3) lineages. The diversity analysis revealed a high level of diversity in the Firmicutes group (K2) both in terms of species richness and evenness (Wilcoxon rank-sum test, p value < 0.05 vs. K1 and K3 groups), consistent with the Ruminococcus enterotype described in Western populations. Additionally, functional enrichment analyses of KEGG modules showed significant differences in abundance between individuals with T2DM and controls (FDR < 0.05). These differences include modules associated with the degradation of amino acids, such as arginine, the degradation of urea as well as those associated with homoacetogenesis. Prediction analysis with the Predomics approach suggested potential biomarkers for T2DM, including a balance between a depletion of Enterococcus faecium and Blautia lineages with an enrichment of Absiella spp or Eubacterium limosum in T2DM individuals, highlighting the potential of metagenomic analysis in predicting predisposition to diabetic cardiomyopathy in T2DM patients.

Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake ( q  < 0.01). Further analyses of the impact of bacterial and fungal genera on Factor1 determined that the nine bacterial genera ( Phocaeicola, Ligilactobacillus, Mesosutterella, Acidaminococcus, Dorea A, CAG-317, Caecibacter, Prevotella and Gemmiger ) and one fungal genus ( Malassezia furfur ) were found to have high factor weights (absolute weight > 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.

Early-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

IntroductionPancreatic ductal adenocarcinoma (PDAC) is a very aggressive cancer. There are various sub-cellular events (both genetic and epigenetic) that get dysregulated leading to tumorigenesis. Methylation in promoters of tumor suppressor genes is one of these epigenetic phenomena contributing to the pathogenesis of cancer. Genes analyzed for promoter methylation status in this study namely SPARC (Secreted Protein Acidic and Rich in Cysteine, UCHL1 (ubiquitin carboxy-terminal hydrolase L1), NPTX2 (neuronal pentraxin 2), PENK (proenkephalin) had been studied in pancreatic cancer, but there is a need to check methylation in these genes as circulatory non-invasive markers. This study analyzed the absolute quantification of methylation levels of SPARC, UCHL1, PENK, and NPTX2 genes promoters in PDAC patients as well as in chronic pancreatitis (CP) patients and healthy subjects (HC) and evaluated its clinical significance in PDAC.Materials and methodsThe study included 65 PDAC patients, 25 CP patients, and 25 healthy controls. DNA was extracted from their plasma samples and subsequently given bisulfite treatment. Absolute quantization of methylated and unmethylated copies of gene promoters of all the four genes was performed using real-time PCR (SYBR green) by the standard curve method. Methylation levels were expressed as methylation index (MI) for each gene in each patient. MI was calculated from absolute copy numbers as follows: MI-methylated copy number/methylated copy number + unmethylated copy number). These indices were used to compare gene methylation levels within different groups and to correlate with clinicopathological features and survival of pancreatic cancer patients. An appropriate statistical analysis was applied.ResultsMethylation indices for all the four genes in PDAC cases were found to be significantly higher as compared to that in healthy individuals. SPARC MI values were found to differentiate early-stage PDAC patients from CP patients. PDAC patients with the metastasized disease and stage IV disease were found to have high MI for the SPARC gene as well as for the NPTX2 gene, while a higher UCHL1 methylation index was found to correlate with an advanced stage of the disease. Higher MI values for SPARC and NPTX2 genes were found to associate with poor survival in patients with PDAC.ConclusionMethylation load in the form of MI for each of the four genes assessed in plasma may emerge as a non-invasive biomarker to differentiate pancreatic cancer from healthy individuals. But only SPARC and NPTX2 hypermethylation were able to distinguish pancreatic cancer from chronic pancreatitis. Association of aberrant methylation in SPARC and NPTX2 gene with metastasis and poor survival of patients suggest the role of methylation in these genes as prognostic markers.

Background Medical schools have the obligation to direct their education toward addressing the priority health concerns of the societies that they serve. The purpose of this study was to evaluate the integration of the concepts and values of social accountability into the case scenarios that are used in a problem-based learning (PBL) curriculum at a medical school in the United Arab Emirates (UAE). Methods A validated “social accountability inventory for PBL” was used for examining 70 case scenarios in a problem-based learning (PBL) medical curriculum. Results The findings of the study showed that patient gender and age were included in all the 70 case scenarios. Vast majority of the case scenarios had successfully integrated the social accountably values in addressing the following: the major health problems or social health concerns of the UAE (73%), the social determinants of health (70%), the contextual integration of medical professionalism (87%), the evolving roles of doctors in the health system (79%), the healthcare referral system based on the case complexity (73%), the involvement of different stakeholders in healthcare (87%), psychosocial issues rather than only the disease-oriented issues (80%) and the values of health promotion/prevention (59%) cases. On the other hand, the case scenarios were deficient in integrating other social accountability values that related to the importance of treatment cost-effectiveness (91%), consideration of the underserved, disadvantaged or vulnerable populations in the society (89%), patient’s ethnicity (77%), multidisciplinary approach to patient management (67%), the socioeconomic statuses of patients (53%), the issues regarding the management of the health system (39%) respectively. There was variability in integrating the social accountability values in case scenarios across different units which are based on organ system. Conclusion Medical educators and healthcare leaders can use this valuable data to calibrate the curriculum content, especially when using a problem-based learning curriculum to integrate the values of social accountability such as relevance, quality, equity and cost-effectiveness to train the future generation of healthcare providers to be ready to address the ever-changing and diverse needs of the societies.

Background Heavy tobacco smoking, a hallmark feature of lung cancer, is drastically predominant in Middle Eastern populations. The precise links between nicotine dependence and the functional contribution of the oral microbiota remain unknown in these populations. Methods We evaluated the composition and functional capabilities of oral microbiota with relation to cigarette smoking in 105 adults through shotgun metagenomics using buccal swabs. Results The oral microbiota composition in our study subjects was dominated by the phyla Firmicutes , Proteobacteria , Actinobacteria , and Bacteroidetes , in addition to the genera Prevotella and Veillonella, similar to previously described westernized cohorts. Furthermore, the smoker's oral microbiota represented a significant abundance of Veillonella dispar , Leptotrichia spp. and Prevotella pleuritidis when compared to non-smokers. Within the smoking groups, differential relative abundance testing unveiled relative abundance of Streptobacillus hongkongensis , Fusobacterium massiliense , Prevotella bivia in high nicotine dependent compared to low nicotine dependent profiles based on Fagerström Test for Nicotine Dependence. Functional profiling showed marked differences between smokers and non-smokers. Smokers exhibited an enrichment of Tricarballylate utilization and Lactate racemization when compared to the non-smokers. According to their nicotine dependence, enrichment of Xanthosine utilization, p-Aminobenzoyl-Glutamate utilization, and multidrug efflux pump in Campylobacter jejuni biosynthesis modules were detected in the high nicotine dependent group. Conclusions These compositional and functional differences may provide critical insight on how variations in the oral microbiota could predispose to respiratory illnesses and smoke cessation relapse in cigarette smokers. In particular, the observed enrichment of Fusobacterium and Prevotella in the oral microbiota possibly suggests an intriguing linkage to gut and lung cancers.

[This corrects the article DOI: 10.1371/journal.pone.0218274.].[This corrects the article DOI: 10.1371/journal.pone.0218274.].

Type 2 diabetes mellitus (T2DM) drastically affects the population of Middle East countries with an ever-increasing number of overweight and obese individuals. The precise links between T2DM and gut microbiome composition remain elusive in these populations. Here, we performed 16 S rRNA and ITS2- gene based microbial profiling of 50 stool samples from Emirati adults with or without T2DM. The four major enterotypes initially described in westernized cohorts were retrieved in this Emirati population. T2DM and non-T2DM healthy controls had different microbiome compositions, with an enrichment in Prevotella enterotype in non-T2DM controls whereas T2DM individuals had a higher proportion of the dysbiotic Bacteroides 2 enterotype. No significant differences in microbial diversity were observed in T2DM individuals after controlling for cofounding factors, contrasting with reports from westernized cohorts. Interestingly, fungal diversity was significantly decreased in Bacteroides 2 enterotype. Functional profiling from 16 S rRNA gene data showed marked differences between T2DM and non-T2DM controls, with an enrichment in amino acid degradation and LPS-related modules in T2DM individuals, whereas non-T2DM controls had increased abundance of carbohydrate degradation modules in concordance with enterotype composition. These differences provide an insight into gut microbiome composition in Emirati population and its potential role in the development of diabetes mellitus.