Ten missteps in the management of inflammatory bowel disease in Asia: An expert report by the Asian Pacific Association of Gastroenterology Working Group on Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra-intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5-ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life-threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti-tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under-recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post-op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn.

Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis.

BACKGROUND: We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region. METHODS: We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I2. The study is registered in PROSPERO, CRD42022339956. FINDINGS: A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I2=96%) for clarithromycin, 52% (49-55; I2=99%) for metronidazole, 26% (24-29; I2=96%) for levofloxacin, 4% (3-5; I2=95%) for tetracycline, and 4% (3-5; I2=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I2=93%) for clarithromycin, 61% (55-66; I2=99%) for metronidazole, 35% (31-39; I2=95%) for levofloxacin, 4% (2-6; I2=96%) for tetracycline, and 6% (4-8; I2=96%) for amoxicillin in the Asia-Pacific region. INTERPRETATION: Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed. FUNDING: Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A Malaysian consensus report on the diagnosis and treatment of Helicobacter pylori infection.

Helicobacter pylori is one of the most common chronic bacterial infections in humans and responsible for 90% of duodenal ulcers and 70-90% of gastric ulcers. Despite this, many misconceptions regarding the appropriate diagnostic method and treatment strategies still exist in the Malaysian clinical practice. Under the initiative of the steering committee, an expert panel consisting of nine key opinion leaders in the field of gastroenterology convened to develop a set of consensus statements that are relevant to the Malaysian healthcare practice. The panel members reviewed the current evidence on the management of H. pylori infection, focusing on the best practices that are relevant to the Malaysian population based on clinical experience and published clinical evidence. Using the modified Delphi method, the panel achieved consensus in three areas of H. pylori infection management: indications for testing, diagnosis, and treatment. The panel proposed a set of 19 consensus statements, which were synthesized via two rounds of blinded voting and group discussions. The recommendations provided are relevant to the Malaysian population and can be used as a guide by physicians across various healthcare settings to facilitate appropriate diagnostic testing and treatment of H. pylori infection.

High Accuracy of a Simplified, Practical Algorithm in Differentiating Crohn's Disease from Intestinal Tuberculosis.

BACKGROUND: The differentiation between intestinal tuberculosis (ITB) and Crohn's disease (CD) remains a challenge, particularly in areas where tuberculosis is highly prevalent. Previous studies have identified features that favour one diagnosis over the other. The aim of the study was to determine the accuracy of a standardized protocol in the initial diagnosis of CD versus ITB. METHODS: All patients with suspected ITB or CD were prospectively recruited. A standardized protocol was applied, and the diagnosis was made accordingly. The protocol consists of history and examination, ileocolonoscopy with biopsies, and tuberculosis workup. The diagnosis of probable ITB was made based on at least one positive finding. All other patients were diagnosed as probable CD. Patients were treated either with anti-tubercular therapy or steroids. Reassessment was then carried out clinically, biochemically, and endoscopically. In patients with suboptimal response, the treatment was either switched or escalated depending on the reassessment. RESULTS: 164 patients were recruited with final diagnosis of 30 (18.3%) ITB and 134 (81.7%) CD. 1 (3.3%) out of 30 patients with ITB was initially treated as CD. 16 (11.9%) out of 134 patients with CD were initially treated as ITB. The initial overall accuracy for the protocol was 147/164 (89.6%). All patients received the correct diagnosis by 12 weeks after reassessment. CONCLUSION: In our population, most patients had CD rather than ITB. The standardized protocol had a high accuracy in differentiating CD from ITB.

Nudix Hydroxylase 15 Mutations Strongly Predict Thiopurine-Induced Leukopenia Across Different Asian Ethnicities: Implications for Screening in a Diverse Population.

Background and Aims: Thiopurines, which are immunosuppressive drugs for maintaining remission for inflammatory bowel disease, are known to cause myelotoxicity in patients with Nudix Hydroxylase 15 (NUDT15) genetic variants in some Asian countries with monoethnic populations. We aimed to investigate the association of NUDT15 variants with leukopenia in a multiethnic population in Southeast Asia. Methods: Patients with a confirmed diagnosis of inflammatory bowel disease were recruited. We collected demographic and clinical characteristics and whole blood counts before and after initiating thiopurines. Thiopurine S-methyltransferase (TPMT) and NUDT15 genotypes were analyzed with the single nucleotide polymorphisms (SNPs) genotyping assay. Leukopenia was defined as a white blood cell (WBC) count < 3,000/µl. Results: In this study, 19 (18.6%) of the 102 patients who had adequate thiopurine therapy experienced leukopenia, 11 patients (57.9%) had NUDT15 c.415C > T variants, 2 patients (10.5%) had NUDT15 c.52G > A variants while one (5.3%) had a TPMT variation. Individually, NUDT15 c.415C > T had a sensitivity and specificity of 57.9% and 94.0% (odds ratio [OR] = 21.45, 95% CI 5.94-77.41, p < 0.001), respectively, for predicting thiopurine-induced leukopenia, while NUDT15 c.52G > A was only observed in patients with leukopenia. As compared with patients with wild-type NUDT15, both NUDT15 variations had a combined sensitivity and specificity of 68.4% and 94%, respectively (OR = 33.80, 95% CI 8.99-127.05, p < 0.001), for predicting thiopurine-induced leukopenia as well as a shorter onset to leukopenia (median onset [months] 2.0 vs. 5.5; p = 0.045). Sub-group analysis showed that both NUDT15 variations were strongly associated with leukopenia among the Chinese and Indians but not among the Malays. Conclusion: Nudix Hydroxylase 15 variants strongly predicted thiopurine-induced leukopenia across a multiethnic Southeast Asian population, particularly among the Chinese and Indians.

Percutaneous endoscopic gastrostomy using the introducer method with ultra-slim endoscopy in amyotrophic lateral sclerosis patients with respiratory compromise: A safe technique.

BACKGROUND AND AIM: Percutaneous endoscopic gastrostomy (PEG) placement is recommended in patients with amyotrophic lateral sclerosis (ALS), but the procedure is considered high risk. In this study, we aimed to compare the outcome of ALS patients with and without PEG. The success of the procedure and complications of PEG insertion were also explored. METHODS: Patients with ALS who met the criteria for enteral feeding support were consecutively recruited. Patients who consented had PEG insertion using the modified technique of introducer method with transoral ultra-slim endoscopy. RESULTS: A total of 64 patients were recruited, of which 36 (56%) patients consented to PEG. The median age of all patients was 65 years and 59% were male. There was no difference in demographic and clinical characteristics between patients who agreed to a PEG and those who did not. The mortality rate at 6 and 12 months was lower in the PEG cohort compared with non-PEG, but this was not statistically significant (6 months: 28.6% vs 32.2%, P = 0.561; 12 months: 38.9% vs 50.0%, P = 0.374). Amongst the PEG cohort, 61% were stratified high risk and 31% moderate risk. Thirty-one percent of them required long-term home noninvasive ventilation. All patients (100%) underwent successful PEG insertion at single attempt using the modified approach. The complications reported over a period of 6 months were infected PEG site (17%), dislodged gastrostomy tube (14%), and minor bleeding (8%). CONCLUSION: In ALS patients with moderate to high risk of PEG insertion, the introducer technique utilizing ultra-slim endoscopy guidance was well tolerated and safe.

Natural history and clinical features of ALS in Malaysia.

OBJECTIVE: Studies from multiethnic populations are rarely reported but do indicate differences in phenotypic presentation and survival in amyotrophic lateral sclerosis (ALS). In this study, we aimed to investigate the natural history of a cohort of ALS patients from a multiethnic population. Methods: Data from ALS patients presenting to our multidisciplinary ALS clinic were prospectively collected from January 2015 to June 2020 as part of an ongoing hospital-based patient registry. Kaplan-Meier and Cox regression model were performed to identify potential prognostic factors. Results: A total of 144 ALS patients were recruited. We estimated the crude ALS incidence as 0.53 per 100,000 for 2019 but rises to 2 per 100,000 in patients aged 60-74 years. The majority of patients were of Chinese ethnicity (59.7%), followed by Malay (24.3%), Indian (11.1%), and others (4.9%). Malaysian Indians had a significantly steeper ALSFRS-R slope at diagnosis (p = 0.040). We found a worse prognosis in patients with bulbar-onset (HR = 1.915, p = 0.019), older age (HR = 1.052, p = 0.000), and who were fast-progressors (HR = 1.274, p = 0.000). In contrast, a higher body mass index (HR = 0.921, p = 0.007) and a longer time to diagnosis (HR = 0.967, p = 0.006), noninvasive ventilation (HR = 0.820, p = 0.000) and percutaneous endoscopic gastrostomy insertion (HR = 0.823, p = 0.000) were associated with better survival. On multivariate analysis, diagnostic delay and slow disease progression were associated with better survival. Conclusions: In our cohort, diagnostic delay and a slow disease progression were significantly associated with better survival in ALS. We also found ethnic variation with Chinese preponderance and more rapid disease progression in patients of Indian descent.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

The Influence of Modernization and Disease on the Gastric Microbiome of Orang Asli, Myanmars and Modern Malaysians.

The present study explored the differences in gastric microbiome between three distinct populations of Southeast Asia. These include the isolated Orang Asli population and modern Malaysians, as well as patients from Myanmar, the least developed country in the region. All 79 subjects recruited in this study had Helicobacter pylori infection. Based on alpha diversity analysis, Orang Asli had the richest and most diverse gastric microbiome, followed by Myanmar and modern Malaysian groups. Beta diversity analysis revealed significant separation of samples between different populations. These observations are likely to be associated with the level of modernization of each population. Our data further suggested increased bacterial species richness and diversity of the gastric microbiome in individuals who were less modernized, particularly in the Orang Asli group, could suppress the growth of H. pylori. In addition, there were significant variations in the gastric microbiome between modern Malaysians with different types of gastric diseases. Notably, Cutibacterium acnes was present at significantly greater abundance level in patients with non-ulcerative dyspepsia than those with peptic-ulcer diagnosis. This suggests that C. acnes may also play a role in gastritis besides H. pylori, which merits further investigation.

Polymorphisms in the host CYP2C19 gene and antibiotic-resistance attributes of Helicobacter pylori isolates influence the outcome of triple therapy.

Objectives: Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors. Methods: Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection). Results: Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C19*2 and CYP2C19*3 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C19*2, CYP2C19*3 and CYP2C19*17 loci. The participants heterozygous for both ABCB1 and CYP2C19*2 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects. Conclusions: Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.

Primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region: a systematic review and meta-analysis.

BACKGROUND: So far, a comprehensive systematic review and meta-analysis has not been done of the prevalence of primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region. We aimed to assess the trends and regional differences in primary antibiotic resistance to H pylori in the Asia-Pacific region and to examine the relation between resistance and first-line eradication. METHODS: We did a systematic review and meta-analysis of primary antibiotic resistance to H pylori and the efficacy of first-line regimens in the Asia-Pacific region. We searched PubMed, Embase, and the Cochrane Library for articles published between Jan 1, 1990, and Sept 30, 2016; we also searched abstracts from international conferences. Both observational studies and randomised controlled trials were eligible for inclusion in the analysis of primary antibiotic resistance, but only randomised controlled trials were eligible for inclusion in the analysis of efficacy of first-line therapies. Meta-analysis was by the random-effects model to account for the substantial variations in resistance across the region. We did subgroup analyses by country and study period (ie, before 2000, 2001-05, 2006-10, and 2011-15) to establish country-specific prevalences of primary antibiotic resistance and first-line eradication rates. This study is registered with PROSPERO, number CRD42017057905. FINDINGS: 176 articles from 24 countries were included in our analysis of antibiotic resistance. The overall mean prevalences of primary H pylori resistance were 17% (95% CI 15-18) for clarithromycin, 44% (95% CI 39-48) for metronidazole, 18% (95% CI 15-22) for levofloxacin, 3% (95% CI 2-5) for amoxicillin, and 4% (95% CI 2-5) for tetracycline. Prevalence of resistance to clarithromycin and levofloxacin rose significantly over time during the period investigated, whereas resistance to other antibiotics remained stable. 170 articles from 16 countries were included in analysis of efficacy of first-line therapies. We noted unsatisfactory efficacy (ie, <80%) with clarithromycin-containing regimens in countries where the clarithromycin resistance rates were higher than 20%. INTERPRETATION: The prevalence of primary antibiotic resistance varied greatly among countries in the Asia-Pacific region, and thus treatment strategy should be adapted relative to country-specific resistance patterns. Clarithromycin-containing regimens should be avoided in countries where the prevalence of clarithromycin resistance is higher than 20%. FUNDING: Ministry of Health and Welfare of Taiwan, Ministry of Science and Technology of Taiwan, and Amity University.

Global Fecal and Plasma Metabolic Dynamics Related to Helicobacter pylori Eradication.

Background:Helicobacter pylori colonizes the gastric mucosa of more than half of the world's population. There is increasing evidence H. pylori protects against the development of obesity and childhood asthma/allergies in which the development of these diseases coincide with transient dysbiosis. However, the mechanism underlying the association of H. pylori eradication with human metabolic and immunological disorders is not well-established. In this study, we aimed to investigate the local and systemic effects of H. pylori eradication through untargeted fecal lipidomics and plasma metabolomics approaches by liquid chromatography mass spectrometry (LC-MS). Results: Our study revealed that eradication of H. pylori eradication (i.e., loss of H. pylori and/or H. pylori eradication therapy) changed many global metabolite/lipid features, with the majority being down-regulated. Our findings primarily show that H. pylori eradication affects the host energy and lipid metabolism which may eventually lead to the development of metabolic disorders. Conclusion: These predictive metabolic signatures of metabolic and immunological disorders following H. pylori eradication can provide insights into dynamic local and systemic metabolism related to H. pylori eradication in modulating human health.

Molecular and Proteomic Analysis of Levofloxacin and Metronidazole Resistant Helicobacter pylori.

Antibiotic resistance in bacteria incurs fitness cost, but compensatory mechanisms may ameliorate the cost and sustain the resistance even under antibiotics-free conditions. The aim of this study was to determine compensatory mechanisms of antibiotic resistance in H. pylori. Five strains of levofloxacin-sensitive H. pylori were induced in vitro to develop resistance. In addition, four pairs of metronidazole-sensitive and -resistant H. pylori strains were isolated from patients carrying dual H. pylori populations that consist of both sensitive and resistant phenotypes. Growth rate, virulence and biofilm-forming ability of the sensitive and resistant strains were compared to determine effects of compensatory response. Proteome profiles of paired sensitive and resistant strains were analyzed by liquid chromatography/mass spectrophotometry (LC/MS). Although there were no significant differences in growth rate between sensitive and resistant pairs, bacterial virulence (in terms of abilities to induce apoptosis and form biofilm) differs from pair to pair. These findings demonstrate the complex and strain-specific phenotypic changes in compensation for antibiotics resistance. Compensation for in vitro induced levofloxacin resistance involving mutations of gyrA and gyrB was functionally random. Furthermore, higher protein translation and non-functional protein degradation capabilities in naturally-occuring dual population metronidazole sensitive-resistant strains may be a possible alternative mechanism underlying resistance to metronidazole without mutations in rdxA and frxA. This may explain the lack of mutations in target genes in ~10% of metronidazole resistant strains.

Assessment of Risk and Sero-Prevalence of Helicobacter pylori Colonization among Remote Orang Asli Tribes in Peninsula Malaysia.

The epidemiology of Helicobacter pylori (H. pylori) infection is related to human poverty with marked differences between developing and developed countries. Socioeconomic factors and living standards are the main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. The aim of this study was to assess the risk and sero-prevalence of H. pylori colonization among Orang Asli in Peninsula Malaysia. This cross-sectional study was conducted on Orang Asli subjects in seven isolated settlements spanning across all three major tribes (Negrito, Proto Malay and Senoi) in Malaysia. Socio-demographic characteristics of the subjects were obtained through interview. Subjects were tested for H. pylori colonization based on CagA and whole cell (WC) antigen serological assays. A total of 275 subjects participated in this study. Among these subjects, 115 (44.7%) were H. pylori sero-positive with highest sero-prevalence among Negrito (65.7%). Among subjects who were H. pylori sero-positive, CagA sero positivity was also significantly higher among Negrito. The highest proportion of respondents reported to be H. pylori sero-positive was from age group 30 years old and below (57.9%), males (56.2%), Negrito (48.6%) and live in bamboo house (92.3%). The highest proportion of respondents reported to be CagA sero-positive was from age group 30 years old and below (41.4%), males (35.6%) and Negrito (48.6%). The results of this study demonstrate that H. pylori colonization can be related to age, gender, tribes and house materials and CagA sero-positive stain closely associated with age, gender and tribes.

Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults.

BACKGROUND: Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome. METHODS: As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18-30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline. RESULTS: We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000-170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders. CONCLUSIONS: Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients.

Polymorphisms at Locus 4p14 of Toll-Like Receptors TLR-1 and TLR-10 Confer Susceptibility to Gastric Carcinoma in Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs) and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs) associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD), 40 with peptic ulcer disease (PUD) and 15 with gastric cancer (GC) subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up-regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease.

Changes in Metabolic Hormones in Malaysian Young Adults following Helicobacter pylori Eradication.

BACKGROUND: More than half of the world's adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study. METHODS: We enrolled 29 H. pylori-positive young adult (18-30 year-old) volunteer subjects to evaluate the effect of H. pylori eradication on meal-associated changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes in body mass index and anthropometric measurements were recorded, pre- and post-eradication therapy. RESULTS: Pre-prandial active amylin, total peptide YY (PYY) and pancreatic polypeptide (PP) levels were significantly elevated 12 months post-eradication compared with baseline (n = 18; Wilcoxon's signed rank test, p<0.05). Four of the post-prandial gut metabolic hormones levels (GLP-1, total PYY, active amylin, PP) were significantly higher 12 months post-eradication compared to baseline (n = 18; p<0.05). Following H. pylori eradication, the BMI and anthropometric values did not significantly change. CONCLUSIONS: Our study indicates that H. pylori eradication was associated with long-term disturbance in three hormones (active amylin, PP and total PYY) both pre- and post-prandially and one hormone (GLP-1) post-prandially. Longer post-eradication monitoring is needed to investigate the long-term impact of the observed hormonal changes on metabolic homeostasis.

Prevalence of serum celiac antibodies in a multiracial Asian population--a first study in the young Asian adult population of Malaysia.

BACKGROUND: Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible persons. The prevalence of CD in Malaysia is unknown. We aim to determine the seroprevalence of CD antibodies and also investigate the correlation between H. pylori infection and CD in the young and healthy multiracial Malaysian population. METHODS: Healthy young adult volunteers between the ages of 18-30 years were consecutively recruited from June 2012 to May 2014 at the University of Malaya Medical Centre (UMMC), Kuala Lumpur. Serum samples from all the participants were tested for anti-gliadin antibody immunoglobulin A/immunoglobulin G (IgA/IgG) and anti-tissue transglutaminase antibody (tTG) IgA/IgG. Samples positive for both anti-gliadin and anti-tTG were further validated for anti-human endomysial IgA antibodies (EmA). Serological diagnosis of CD was made when anti-gliadin, anti-tTG and anti-EmA were positive. RESULTS: 562 qualified participants with mean age 24 ± 2.4 years old were recruited into our study. CD was found in 7 participants where most of them were asymptomatic and unaware of their CD status. The median of anti-gliadin and anti-tTG IgA/IgG value was 38.2 U/ml (interquartile range, 28.3-60.4 U/ml) and 49.2 U/ml (interquartile range, 41.1-65.9 U/ml), respectively. Seroprevalence of CD antibodies was 1.9% (6 out of 324) in female while only 0.4% (1 out of 238) in male. Seroprevalence among Malay was 0.8% (2 of 236), Chinese was 1.7% (3 of 177) and Indian was 1.3% (2 of 149). Overall, seroprevalence of CD antibodies in healthy asymptomatic adults in the Malaysian population was 1.25% (95% CI, 0.78%-1.72%). No significant relationship was discovered between CD and H. pylori infection. CONCLUSIONS: The seroprevalence of CD antibodies in healthy young adults in the Malaysian population was 1.25% (1 in 100). CD is underdiagnosed and it could be a much greater problem in Malaysia than previously thought.

Functional and molecular surveillance of Helicobacter pylori antibiotic resistance in Kuala Lumpur.

BACKGROUND: Helicobacter pylori is the etiological agent for diseases ranging from chronic gastritis and peptic ulcer disease to gastric adenocarcinoma and primary gastric B-cell lymphoma. Emergence of resistance to antibiotics possesses a challenge to the effort to eradicate H. pylori using conventional antibiotic-based therapies. The molecular mechanisms that contribute to the resistance of these strains have yet to be identified and are important for understanding the evolutional pattern and selective pressure imposed by the environment. METHODS AND FINDINGS: H. pylori was isolated from 102 patients diagnosed with gastrointestinal diseases, who underwent endoscopy at University Malaya Medical Centre (UMMC). The isolates were tested for their susceptibility on eleven antibiotics using Etest. Based on susceptibility test, 32.3% of the isolates were found to have primary metronidazole resistance; followed by clarithromycin (6.8%) and fluoroquinolones (6.8%). To further investigate the resistant strains, mutational patterns of gene rdxA, frxA, gyrA, gyrB, and 23S rRNA were studied. Consistent with the previous reports, metronidazole resistance was prevalent in the local population. However, clarithromycin, fluoroquinolone and multi-drug resistance were shown to be emerging. Molecular patterns correlated well with phenotypic data. Interestingly, multi-drug resistant (MDR) strains were found to be associated with higher minimum inhibitory concentration (MIC) than their single-drug resistant (SDR) counterparts. Most importantly, clarithromycin-resistant strains were suggested to have a higher incidence for developing multi-drug resistance. CONCLUSION: Data from this study highlighted the urgency to monitor closely the prevalence of antibiotic resistance in the Malaysian population; especially that of clarithromycin and multi-drug resistance. Further study is needed to understand the molecular association between clarithromycin resistance and multi-drug resistance in H. pylori. The report serves a reminder that a strict antibiotic usage policy is needed in Malaysia and other developing countries (especially those where H. pylori prevalence remained high).