Molecular characterization and prevalence of antibiotic resistance in Helicobacter pylori isolates in Kuala Lumpur, Malaysia

Acknowledgment We would like to thank the Universiti Kebangsaan Malaysia for providing both the permission and the facilities to conduct and publish this research. The research was funded by a grant from Universiti Kebangsaan Malaysia under Economic Transformation Programme Research Fund Scheme (grant no. ETP-2013-042).Peer reviewedPublisher PD

Irritable bowel syndrome and inflammatory bowel disease overlap syndrome: pieces of the puzzle are falling into place

Irritable bowel syndrome (IBS), a common gastrointestinal disorder involving the gut-brain axis, and inflammatory bowel disease (IBD), a chronic relapsing inflammatory disorder, are both increasing in incidence and prevalence in Asia. Both have significant overlap in terms of symptoms, pathophysiology, and treatment, suggesting the possibility of IBS and IBD being a single disease entity albeit at opposite ends of the spectrum. We examined the similarities and differences in IBS and IBD, and offer new thoughts and approaches to the disease paradigm

Diffuse large B-cell lymphoma of the small intestine in a patient with refractory coeliac disease.

INTRODUCTION: Coeliac disease enteropathy is associated with an increased risk of lymphomas. Enteropathy-associated T-cell lymphoma is the principal malignancy related to coeliac disease. However, studies have shown that other types of lymphoma such as diffuse large B-cell lymphoma may also be associated with coeliac disease. CASE REPORT: We report a 54-year-old Caucasian man who presented with chronic diarrhoea and weight loss. He was diagnosed with coeliac disease based on positive serology results and duodenal, jejunal, and ileal biopsies that showed villous atrophy. Despite adherence to a gluten-free diet, there was no clinical remission and enteropathy-associated T cell lymphoma was suspected. Repeated endoscopic biopsy showed persistent mucosal disease but no evidence of lymphoma. Several weeks later he presented with a perforated jejunum. Histology of the resected jejunum showed diffuse infiltration of submucosa and muscularis propria by malignant lymphoid cells sparing the mucosa. The cells expressed CD20, CD79α, CD10 and BCL6 and ki67 of 80%, consistent with diffuse large B-cell lymphoma. DISCUSSION: It is suspected that the undetected lymphoma may have contributed to the persistent malabsorption syndrome rendering the patient unresponsive to treatment. Despite thorough clinical and endoscopic evaluation and multiple biopsies, histologic diagnosis of DLBCL was only confirmed following resection of the perforated jejunu

Therapeutic monitoring of thiopurine metabolites : validation of an HPLC method and preliminary findings from a small cohort of Malaysian patients with inflammatory bowel disease

Thiopurine therapy of inflammatory bowel disease (IBD) is guided by the relative blood concentrations 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP). However, their action is altered by in vivo phosphorylation, and this is not normally measured in clinical studies. Hence, we trialled a novel method for profiling phosphorylated thiopurine metabolites and revisited the association between thiopurine metabolites and IBD treatment outcomes. We first optimised and validated a published high-performance liquid chromatography (HPLC) method for measuring the blood levels of thioguanosine monophosphate (TGMP), thioguanosine diphosphate (TGDP), thioguanosine triphosphate (TGTP), and methylthioinosine monophosphate (MeTIMP). Then, we assembled a small cohort of IBD patients (n = 20), who had been treated with azathioprine for at least three months, and obtained blood samples for analysis of the metabolites. The patients received treatments at the Universiti Kebangsaan Malaysia Specialist Centre between March 2018 and April 2019. They were classified as responders (n = 12) or non-responders (n = 6) to azathioprine based on their disease activity scores (CDAI or Mayo score). The HPLC method was precise with intraday and interday variation < 15% for all the tested metabolites, and the relative accuracy ranged from 40.2 to 114.0%. We noted that the responders had higher median 6-TGN but lower median TGTP levels than the non-responders. However, the differences were not statistically significant (Wilcoxon rank-sum tests; 6-TGN, p = 0.925; TGTP, p = 0.189). The higher median 6-TGN level detected in the responders is in keeping with the findings of prior studies, suggesting that HPLC analysis of phosphorylated thiopurine metabolites is both technically feasible and clinically useful

Chronic consumption of fructose dysregulates genes related to glucose and lipid metabolism in prostate tissue

Fructose is commonly used as a taste enhancer in many processed foods. Excessive fructose consumption is highly associated with obesity and development of cancer particularly prostate cancer. This study aimed to investigate the biochemical and molecular changes in the prostate tissue of rats treated with 20% fructose for six months. A total of 18 rats weighted 200-250 g were divided into two groups, where each group consisted of 9 rats. Control group is given normal diet, while the treated group was given normal diet and 20% fructose in drinking water. After six months of treatment, both groups were sacrificed for further analysis. Body weight, blood pressure and glucose were measured. Lipid profiles were determined using quantitative colorimetric assay. Transcripts level of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), leptin (LEP), angiopoietin 1 (ANGPT1), microRNA (miR)-34a, miR-10b and miR-192 were determined using quantitative PCR, while the protein levels of 11β-HSD1 and leptin were determined using ELISA. The results showed that 20% fructose diet significantly increased blood glucose level as compared to the control (p<0.05). The transcript levels of LEP and miR-192 were significantly lower in the fructose-treated group as compared to the control (p<0.05). There was a significant linear relationship between prostate LEP and serum LDL/VLDL level as well as between the level of prostate LEP and serum total cholesterol level (p<0.05). Thus, our results showed that chronic consumption of fructose could down-regulate LEP and miR-192 expression in prostate tissue, and promote higher accumulation of fat in the tissue. Additionally, downregulation of miR-192 has been reported to be associated with the pathogenesis of prostate cancer. Thus, it can be concluded that long-term fructose diet leads to higher blood glucose level and down-regulation of LEP and miR-192 expression in prostate tissue

Management of refractory heartburn: are we convinced that surgery is better than medical treatment?

In a nutshell, this was a single centre, randomised-controlled trial comparing surgical vs medical modality in treating protonpump inhibitor (PPI)-refractory heartburn; a common condition where optimal treatment approach is not known. All patients referred to the Veterans Affairs gastroenterology clinics for refractory heartburn were screened. Eligible patients would complete the gastro-oesophageal refl ux disease (GORD) – Health Related Quality of Life (GORD-HRQL) questionnaire followed by 2-week trial of omeprazole at a dose of 20 mg twice daily, after which the GORD-HRQL was repeated. Patients who did not show improvement (i.e. decrease of >50% in the initial GORD-HRQL score) then underwent endoscopy with biopsies from the lower oesophagus, but also oesophageal manometry and intraluminal impedance– pH monitoring while continuing omeprazole at the same dose and frequency. Patients with severe refl ux oesophagitis, nonGORD endoscopic abnormalities, oeosinophilic oesophagitis, achalasia or absent contractility were excluded. Other patientreported outcomes included depression, anxiety and health function

The Link Between The Opportunistic Gut Fungal Pathogens With Colorectal Adenocarcinoma

In Malaysia, colorectal cancer (CRC) is highly prevalent. The complex etiopathogenesis of CRC involves gut mycobiome. To date, little has been known about the composition and characteristics of the gut mycobiome in Malaysian CRC patients. We aimed to explore the presence of gut fungal pathogens in CRC patients

Methods for identification of the opportunistic gut mycobiome from colorectal adenocarcinoma biopsy tissues

Colorectal cancer poses a significant threat to global health, necessitating the development of effective early detection techniques. However, the potential of the fungal microbiome as a puta- tive biomarker for the detection of colorectal adenocarcinoma has not been extensively explored. We analyzed the viability of implementing the fungal mycobiome for this purpose. Biopsies were collected from cancer and polyp patients. The total genomic DNA was extracted from the biopsy samples by utilizing a comprehensive kit to ensure optimal microbial DNA recovery. To character- ize the composition and diversity of the fungal mycobiome, high-throughput amplicon sequencing targeting the internal transcribed spacer 1 (ITS1) region was proposed. A comparative analysis re- vealed discrete fungal profiles among the diseased groups. Here, we also proposed pipelines based on a predictive model using statistical and machine learning algorithms to accurately differentiate colorectal adenocarcinoma and polyp patients from normal individuals. These findings suggest the utility of gut mycobiome as biomarkers for the detection of colorectal adenocarcinoma. Ex- panding our understanding of the role of the gut mycobiome in disease detection creates novel opportunities for early intervention and personalized therapeutic strategies for colorectal cancer

Immunophenotyping of gastritis, gastric ulcer and gastric cancer using a cluster of differentiation (CD) antibody microarray

One of the factors that contribute to the development of gastric cancer is the host immune response. Extensive immunophenotype of gastric cancer can be identified by using antibody microarray technique that profiles more than 100 cluster of differentiation (CD) antigens in parallel. In this study, we used DotScanTM antibody microarray to profile CD antigen expression in patients with distinct digestive diseases for surface antigen disease-signatures. Patients’ blood samples with gastric disorders and healthy controls were taken and processed for leukocytes isolation using Histopaque density gradient centrifugation. Leukocytes were captured onto DotScanTM slides and cell binding densities were analyzed using DotReaderTM. Different groups of gastric diseases were found to be characterized by differentially expressed distinct CD antigens. Compared to normal healthy controls, 17, two and four highly expressed CD antigens were identified in gastritis, gastric ulcer and gastric cancer patients, respectively. The 17 CD antigens that show differential expression in gastritis were CD15, CD16, CD20, CD23, CD24, CD25, CD28, CD34, CD37, CD77, CD102, CD103, CD122, CD128, CD10, CD183, and CD184. High expression of CD64 and CD69 were found in gastric ulcer, whereas CD52, CD126, CD135, and CD121a were highly expressed in gastric cancer. CD antigens involve in T-cell functions had reduced expression in gastric cancer, while proinflammatory cytokines shows increased expression. These results demonstrate specific immunophenotype of CD antigens in patients with various gastric diseases and identification of differential expressed surface antigens may have clinical significance for diagnostic and therapeutic purposes

Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer

Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of earlyonset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC