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BACKGROUND: Infection with Helicobacter pylori as the cause of gastric cancer is a global public health concern. In addition to protecting germs from antibiotics, biofilms reduce the efficacy of H. pylori eradication therapy. The nucleotide polymorphisms (SNPs) related with the biofilm forming phenotype of Helicobacter pylori were studied. RESULTS: Fifty-six H. pylori isolate from Bangladeshi patients were included in this cross-sectional study. Crystal violet assay was used to quantify biofilm amount, and the strains were classified into high- and low-biofilm formers As a result, strains were classified as 19.6% high- and 81.4% low-biofilm formers. These phenotypes were not related to specific clades in the phylogenetic analysis. The accessories genes associated with biofilm from whole-genome sequences were extracted and analysed, and SNPs among the previously reported biofilm-related genes were analysed. Biofilm formation was significantly associated with SNPs of alpA, alpB, cagE, cgt, csd4, csd5, futB, gluP, homD, and murF (P < 0.05). Among the SNPs reported in alpB, strains encoding the N156K, G160S, and A223V mutations were high-biofilm formers. CONCLUSIONS: This study revealed the potential role of SNPs in biofilm formation and proposed a method to detect mutation in biofilm from whole-genome sequences.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/genética , Estudos Transversais , Filogenia , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológicoRESUMO
Helicobacter pylori infection is a major cause of intestinal metaplasia. In this study, we aimed to understand the reason underlying the low grade and incidence of intestinal metaplasia in Indonesia, based on the expression of genes encoding proinflammatory cytokines in gastric biopsy specimens. The possible reasons for the lesser virulence of the East-Asian-type CagA in Indonesia than that of the Western-type CagA, which is not common in other countries, were also investigated. The mRNA expression of cytokines was evaluated using real-time PCR. CagA characteristics were analyzed using in silico analysis. The expression of cytokines was typically not robust, among H. pylori-infected subjects in Indonesia, despite them predominantly demonstrating the East-Asian-type CagA. This might partially be explained by the characteristics of the East-Asian-type CagA in Indonesia, which showed a higher instability index and required higher energy to interact with proteins related to the cytokine induction pathway compared with the other types (p < 0.001 and p < 0.05, respectively). Taken together, besides the low prevalence of H. pylori, the low inflammatory response of the host and low CagA virulence, even among populations with high infection rates, may play an essential role in the low grade and low incidence of intestinal metaplasia in Indonesia. We believe that these findings would be relevant for better understanding of intestinal metaplasia, which is closely associated with the development of gastric cancer.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/complicações , Citocinas , Indonésia , Biópsia , Neoplasias Gástricas/patologia , Metaplasia/complicações , Metaplasia/patologiaRESUMO
BACKGROUND: In the recent studies, a less virulent Helicobacter pylori variant could still colonize the human stomach and induce gastric inflammation, suggesting the involvement of other virulence factors, such as TlyA hemolysin. Nevertheless, the association of TlyA in the pathogenesis of H. pylori infection remains unclear. We investigated the tlyA profile and determined its relationship with gastritis severity. METHODS: An observational study was conducted using DNA stocks and secondary data from previous studies. The tlyA variant was examined by NGS and confirmed with polymerase chain reaction. Gastritis severity was categorized by the Updated Sydney System. The relationship between a variant of tlyA and gastritis severity was determined, in which discrete variables were tested using the χ2 test or Fisher exact test. RESULTS: Two H. pylori tlyA variants were observed and characterized as tlyA1 and tlyA2. We noted a unique variant in the amino acid sequence 32-35 that is exclusively detected among H. pylori isolated from the Papua island. In addition, we observed that the tlyA variant had a significant association with the H. pylori density in the antral (p = 0.002). Histological analyses revealed that TlyA1 was associated with higher H. pylori density than TlyA2. However, we did not observe any significant association of tlyA with the infiltration of inflammation cells. CONCLUSIONS: We observed 2 tlyA variants (tlyA1 and tlyA2). A significant association of tlyA with bacterial density suggested that tlyA plays a more significant role in the colonization process than its influence on the severity of inflammation in gastric mucosa.
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Gastrite , Infecções por Helicobacter , Helicobacter pylori , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Mucosa Gástrica/patologia , Gastrite/metabolismo , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Inflamação/patologiaRESUMO
Background: Chronic dyspepsia's symptoms are frequently seen in primary to tertiary healthcare in Indonesia. This study aimed to describe the potential usability of pepsinogen (PG) values in determining gastric mucosal conditions, including superficial gastritis and atrophic gastritis. Materials and Methods: We recruited 646 adult dyspeptic patients and then analyzed PG values (including PGI, PGII, and PGI/II ratio) with endoscopic findings, gastric mucosal damages, and Helicobacter pylori infection. The gastric mucosal damage and H. pylori infection were evaluated using histological examination based on the updated Sydney system. Results: Among 646 enrolled patients, 308 (47.2%), 212 (32.8%), 91 (14.1%), 34 (5.2%), and 1 (0.2%) patient were diagnosed with normal mucosa, gastritis, reflux esophagitis, peptic ulcer disease, and gastric cancer, respectively. Significant differences in PGI, PGII, and PGI/II ratio values were observed among ethnic groups (all P < 0.01). The PGI and PGII levels were significantly higher and PGI/II was significantly lower in H. pylori-infected patients than in uninfected ones (all P < 0.001). The optimal cutoff value for PGII and PGI/II was 12.45 ng/mL with an area under the curve (AUC) value of 0.755 (0.702-0.811), sensitivity 59.3%, and specificity 77.1%; and 4.75 with AUC value of 0.821 (0.763-0.855), sensitivity 81.5%, and specificity 78.7%, respectively, to determine moderate-severe atrophy. Conclusion: Serum PG levels, a useful biomarker, represent the endoscopic findings, especially for reflux esophagitis. In addition, the benefits of PG values detecting atrophic gastritis were limited to moderate-severe atrophic gastritis. This usefulness requires careful attention for several ethnic groups in Indonesia.
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Currently, Western-type CagA is used in most commercial Helicobacter pylori CagA ELISA kits for CagA detection rather than East Asian-type CagA. We evaluated the ability of the East Asian-type CagA ELISA developed by our group to detect anti-CagA antibody in patients infected with different cagA genotypes of H. pylori from four different countries in South Asia and Southeast Asia. The recombinant CagA protein was expressed and later purified using GST-tag affinity chromatography. The East Asian-type CagA-immobilized ELISA was used to measure the levels of anti-CagA antibody in 750 serum samples from Bhutan, Indonesia, Myanmar, and Bangladesh. The cutoff value of the serum antibody in each country was determined via Receiver-Operating Characteristic (ROC) analysis. The cutoff values were different among the four countries studied (Bhutan, 18.16 U/mL; Indonesia, 6.01 U/mL; Myanmar, 10.57 U/mL; and Bangladesh, 6.19 U/mL). Our ELISA had better sensitivity, specificity, and accuracy of anti-CagA antibody detection in subjects predominantly infected with East Asian-type CagA H. pylori (Bhutan and Indonesia) than in those infected with Western-type CagA H. pylori predominant (Myanmar and Bangladesh). We found positive correlations between the anti-CagA antibody and antral monocyte infiltration in subjects from all four countries. There was no significant association between bacterial density and the anti-CagA antibody in the antrum or the corpus. The East Asian-type CagA ELISA had improved detection of the anti-CagA antibody in subjects infected with East Asian-type CagA H. pylori. The East Asian-type CagA ELISA should, therefore, be used in populations predominantly infected with East Asian-type CagA.
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Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Genótipo , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Adulto JovemRESUMO
BACKGROUND: The profile of gastric mucosal microbiota has not yet been described in the Indonesian population where the prevalence of Helicobacter pylori is low. METHODS: This is a cross-sectional study analyzing 16S rRNA of 137 gastric biopsy specimens. We analyzed the association between gastric microbiota, H. pylori infection, and gastric mucosal damage. RESULT: Among 137 analyzed samples, 27 were H. pylori-positive and 110 were H. pylori -negative based on culture, histology, and 16S rRNA gene analysis. Significantly lower α-diversity parameters, including Pielou's index, was observed in H. pylori-infected individuals compared with noninfected individuals (all P < .001). Among H. pylori-negative individuals, the permutational analysis of variance of Bray-Curtis dissimilarity distances showed a significant association with different ethnicities, suggesting some ethnic groups had specific microbiota profiles based on the presence of different operational taxonomic units. The linear discriminant analysis effect size (LEfSe) of the H. pylori-negative group showed significant associations between the presence of Micrococcus luteus and Sphingomonas yabuuchiae with Timor and Papuan ethnicities, respectively. The presence of Bulledia sp and Atopobium sp was associated with the Javanese ethnicity. We observed lower α-diversity scores in individuals with gastric mucosal damage and profiles with high abundances of Paludibacter sp and Dialister sp based on LEfSe analysis. CONCLUSION: Our findings suggest the presence of H. pylori is more correlated with a distinct microbiome profile than ethnic precedence.
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Microbioma Gastrointestinal , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , Etnicidade/estatística & dados numéricos , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroenteropatias/etnologia , Gastroenteropatias/microbiologia , Gastroenteropatias/patologia , Infecções por Helicobacter/etnologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Indonésia/epidemiologia , Indonésia/etnologia , Masculino , Pessoa de Meia-IdadeRESUMO
The growing resistance to amoxicillin (AMX)-one of the main antibiotics used in Helicobacter pylori eradication therapy-is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene from strain KIN76. Transformants were subjected to genomic exploration and antimicrobial susceptibility testing. The resistance was transformable, and the presence of two to four PBP1A mutations (T558S and N562H, or T593A and G595S), rather than separate single mutations, was necessary to synergistically increase the AMX MIC up to 16-fold compared with the wild-type (WT) strain 26695. An AMX binding assay of PBP1A was performed using these strains, and binding was visualized by chasing Bocillin, a fluorescent penicillin analog. This revealed that all four-mutation allele-transformed strains exhibited decreased affinity to AMX on PBP1A than the WT. Protein structure modeling indicated that functional modifications occur as a result of these amino acid substitutions. This study highlights a new synergistic AMX resistance mechanism and establishes new markers of AMX resistance in H. pylori.IMPORTANCEThe development of resistance to antibiotics, including amoxicillin, is hampering the eradication of Helicobacter pylori infection. The identification of mechanisms driving this resistance is crucial for the development of new therapeutic strategies. We have demonstrated in vitro the synergistic role of novel mutations in the pbp1 gene of H. pylori that is suspected to drive amoxicillin resistance. Also deepening our understanding of amoxicillin resistance mechanisms, this study establishes new molecular markers of amoxicillin resistance that may be useful in molecular-based antibiotic susceptibility testing approaches for clinical practice or epidemiologic investigations.
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Substituição de Aminoácidos , Amoxicilina , Antibacterianos , Farmacorresistência Bacteriana , Helicobacter pylori , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas , Helicobacter pylori/genética , Helicobacter pylori/efeitos dos fármacos , Proteínas de Ligação às Penicilinas/genética , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Mutação , Humanos , Infecções por Helicobacter/microbiologia , Proteínas de Bactérias/genéticaRESUMO
Helicobacter pylori antimicrobial resistance is a critical public health issue. Typically, antimicrobial resistance epidemiology reports include only the antimicrobial susceptibility test results for H. pylori. However, this phenotypic approach is less capable of answering queries related to resistance mechanisms and specific mutations found in particular global regions. Whole genome sequencing can help address these two questions while still offering quality control and is routinely validated against AST standards. A comprehensive understanding of the mechanisms of resistance should improve H. pylori eradication efforts and prevent gastric cancer.
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Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as pbp1a, rdxA, ribF, fur, gyrA, gyrB, 23S rRNA, and infB) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher's exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance (p = 0.000018) but not in locus A2146G (p = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) (p = 0.002) and N87K (p = 0.002) of gyrA was associated with levofloxacin resistance. Mutations in locus A343V (p = 0.041) of gyrB also showed a significant association. Meanwhile, in the pbp1a gene, several mutations might explain the resistance; they were G594fs (p = 0.036), K306R (p = 0.036), N562Y (p = 0.0006), and V45I (p = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in rdxA genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in H. pylori.
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We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the 'Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)', while ARG-ACC-the ARG in the accessory genome-are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype.
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Single-nucleotide polymorphisms (SNPs) in various human genes are key factors in carcinogenesis. However, whether SNPs in bacterial pathogens are similarly crucial in cancer development is unknown. Here, we analyzed 1,043 genomes of the stomach pathogen Helicobacter pylori and pinpointed a SNP in the serine protease HtrA (position serine/leucine 171) that significantly correlates with gastric cancer. Our functional studies reveal that the 171S-to-171L mutation triggers HtrA trimer formation and enhances proteolytic activity and cleavage of epithelial junction proteins occludin and tumor-suppressor E-cadherin. 171L-type HtrA, but not 171S-HtrA-possessing H. pylori, inflicts severe epithelial damage, enhances injection of oncoprotein CagA into epithelial cells, increases NF-κB-mediated inflammation and cell proliferation through nuclear accumulation of ß-catenin, and promotes host DNA double-strand breaks, collectively triggering malignant changes. These findings highlight the 171S/L HtrA mutation as a unique bacterial cancer-associated SNP and as a potential biomarker for risk predictions in H. pylori infections.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Serina Proteases/genética , Serina Proteases/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Antígenos de Bactérias/metabolismoRESUMO
Helicobacter pylori is involved in the etiology and severity of several gastroduodenal diseases; however, plasticity of the H. pylori genome makes complete genome assembly difficult. We report here the full genomes of H. pylori strains CHC155 and VN1291 isolated from a non-cardia gastric cancer patient and a duodenal ulcer patient, respectively, and their virulence demonstrated by in vitro infection. Whole-genome sequences were obtained by combining long- and short-reads with a hybrid-assembly approach. Both CHC155 and VN1291 genome possessed four kinds of genomic island: a cag pathogenicity island (cagPAI), two type 4 secretion system islands within an integrative and conjugative element (tfs ICE), and prophage. CHC155 and VN1291 carried East Asian-type cagA and vacA s1m1, and outer membrane protein genes, including two copies of oipA. Corresponded to genetic determinants of antibiotic resistance, chromosomal mutations were identified in CHC155 (rdxA, gyrA, and 23S rRNA) and VN1291 (rdxA, 23S rRNA, and pbp1A). In vitro infection of AGS cells by both strains induced the cell scattering phenotype, tyrosine phosphorylation of CagA, and promoted high levels of IL8 secretion, indicating fully intact phenotypes of the cagPAI. Virulence genes in CHC155 and VN1291 genomes are crucial for H. pylori pathogenesis and are risk factors in the development of gastric cancer and duodenal ulcer. Our in vitro studies indicate that the strains CHC155 and VN1291 carry the pathogenic potential.
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Úlcera Duodenal , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Úlcera Duodenal/microbiologia , Genômica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , RNA Ribossômico 23S , População do Sudeste Asiático , Neoplasias Gástricas/microbiologiaRESUMO
INTRODUCTION: Patients with chronic renal disease (CKD) are at a significantly elevated risk for ventricular arrhythmia. Several electrocardiographic (ECG) methods can be used to assess the ventricular arrhythmia risk on the standard 12-lead ECG.
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Falência Renal Crônica , Humanos , Diálise Renal , Eletrocardiografia , PacientesRESUMO
Evaluation of Helicobacter pylori resistance to antibiotics is crucial for treatment strategy in Myanmar. Moreover, the genetic mechanisms involved remain unknown. We aimed to investigate the prevalence of H. pylori infection, antibiotic resistance, and genetic mechanisms in Myanmar. One hundred fifty patients from two cities, Mawlamyine (n = 99) and Yangon (n = 51), were recruited. The prevalence of H. pylori infection was 43.3% (65/150). The successfully cultured H. pylori isolates (n = 65) were tested for antibiotic susceptibility to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline by Etest, and the resistance rates were 80%, 33.8%, 7.7%, 4.6%, and 0%, respectively. In the multidrug resistance pattern, the metronidazole-levofloxacin resistance was highest for double-drug resistance (16/19; 84.2%), and all triple-drug resistance (3/3) was clarithromycin-metronidazole-levofloxacin resistance. Twenty-three strains were subjected to next-generation sequencing to study their genetic mechanisms. Interestingly, none of the strains resistant to clarithromycin had well-known mutations in 23S rRNA (e.g., A2142G, A2142C, and A2143G). New type mutation genotypes such as pbp1-A (e.g., V45I, S/R414R), 23S rRNA (e.g., T248C), gyrA (e.g., D210N, K230Q), gyrB (e.g., A584V, N679H), rdxA (e.g., V175I, S91P), and frxA (e.g., L33M) were also detected. In conclusion, the prevalence of H. pylori infection and its antibiotic resistance to metronidazole was high in Myanmar. The H. pylori eradication regimen with classical triple therapy, including amoxicillin and clarithromycin, can be used as the first-line therapy in Myanmar. In addition, next-generation sequencing is a powerful high-throughput method for identifying mutations within antibiotic resistance genes and monitoring the spread of H. pylori antibiotic-resistant strains.
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BACKGROUND: We evaluated the microbiota in the stomach of Gastroesophageal Reflux Disease (GERD) patients. We compared Erosive Reflux Disease (ERD) to gastritis and Non-erosive Reflux Disease (NERD) subjects by 16S rRNA approach on gastric biopsy specimens. A total of 197 subjects were included consisting of gastritis (68; 34.52%), ERD (55; 27.92%), and NERD (74; 37.56%). After quality filtering, 187 samples were included for OTU analysis using Qiime2. RESULTS: We observed a significant difference in alpha diversity (Shannon and Simpson indexes were P = 0.0016 and P = 0.017, respectively). A significant decrease in alpha diversity index was observed in NERD with Helicobacter pylori (H. pylori)-positive subjects than in gastritis (Simpson index P = 0.022; Shannon index P = 0.029), indicating a significant influence of H. pylori on the diversity in the stomach despite the diseases. In H. pylori-negative samples, alpha diversity measurement by the abundance coverage estimates (ACE) and Fisher Test revealed that ERD had significantly lower richness than gastritis and NERD groups (P = 0.00012 and P = 0.00043, respectively). Anaerobacillus sp. could only be found in ERD patients by LEFse analysis. CONCLUSIONS: The presence of ERD could alter microbiome diversity. A negative correlation between H. pylori and ERD is shown in this microbiome study but not in NERD.
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BACKGROUND: Obesity is one of the significant health problems. Physical activity includes a potential modifier in the development of abdominal obesity. OBJECTIVE: The objective of the study is to analyze the association between physical activity and abdominal obesity in middle-aged adults in the Indonesian rural population. METHODS: A community-based study was conducted in a rural area of Malang, Indonesia. Data were collected using interviews to obtain sociodemographic and physical activity index (PAI). Waist circumference was measured using a tape measure. Data were analyzed using one-way ANOVA and logistic regression. RESULTS: A total of 75 adults (62.7% were female) was included in this study. Mean waist circumference was 88.18 ± 9.21 cm. Total prevalence of abdominal obesity was 69.3%. Among the total of participants, 29.3% were inactive. A significant association was found between physical activity and abdominal obesity. Participants with inactive PAI have a higher risk of suffering from abdominal obesity than those with active PAI with odds ratio = 7.04; 95% confidence interval: 1.55-31.99. CONCLUSION: In middle-aged adults living in a rural area of Indonesia, physical activity was associated with a lower risk of abdominal obesity. Strategies for preventing and reducing abdominal obesity in rural areas should consider improving physical activity.
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Although millions of people have been infected by Helicobacter pylori (H. pylori), only a small proportion of infected individuals will develop adverse outcomes, ranging from chronic gastritis to gastric cancer. Advanced development of the disease has been well-linked with chronic inflammation, which is significantly impacted by the adaptive and humoral immunity response. From the perspective of cellular immunity, this review aims to clarify the intricate axis between IL-17, IL-21, and IL-23 in H. pylori-related diseases and the pathogenesis of inflammatory gastrointestinal diseases. CD4+ helper T (Th)-17 cells, with the hallmark pleiotropic cytokine IL-17, can affect antimicrobial activity and the pathogenic immune response in the gut environment. These circumstances cannot be separated, as the existence of affiliated cytokines, including IL-21 and IL-23, help maintain Th17 and accommodate humoral immune cells. Comprehensive understanding of the dynamic interaction between molecular host responses in H. pylori-related diseases and the inflammation process may facilitate further development of immune-based therapy.
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Gastrite/etiologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Interleucinas/metabolismo , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/metabolismo , HumanosRESUMO
Helicobacter pylori infects more than half the human population. However, the prevalence in Indonesia is low, as is the prevalence of gastric cancer. Hence, it could be instructive to compare these prevalence rates and their determining factors with those of countries that have high gastric cancer incidence. Ethnicity and genetic characteristics of H. pylori are important determinants of the H. pylori infection rate in Indonesia. The infection rate is higher in Bataknese, Papuans and Buginese than in Javanese, the predominant ethnic group. Ethnicity is also an important determinant of the genetic characteristics of H. pylori. Analysis of CagA in the EPIYA segment showed that the predominant genotypes in Papuans, Bataknese and Buginese are ABB-, ABDand ABC-type CagA, respectively. Meanwhile, in the countries with high gastric cancer incidence, almost all strains had East Asian type CagA. An antibiotic susceptibility evaluation showed that the standard triple therapy can still be used with caution in several cities. There is a very high rate of resistance to second-line regimens such as levofloxacin and metronidazole. Recent studies have shown that furazolidone, rifabutin and sitafloxacin are potential alternative treatments for antibiotic-resistant H. pylori infection in Indonesia. Rather than focusing on early detection and eradication as in countries with high gastric cancer prevalence, countries with low gastric cancer prevalence should focus on screening the several groups that have a high risk of gastric cancer.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antígenos de Bactérias , Proteínas de Bactérias , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Humanos , Incidência , Indonésia/epidemiologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologiaRESUMO
The use of serum anti-Helicobacter pylori IgG and pepsinogen (PG) detection as a diagnostic method was evaluated in Sri Lanka. Gastric biopsies were performed (353 patients), and the prevalence of H. pylori infection was 1.7% (culture) and 2.0% (histology). IgG serology testing showed an area under the curve (AUC) of 0.922 (cut-off, 2.95 U/mL; specificity, 91.56%; sensitivity, 88.89%). Histological evaluation showed mild atrophy (34.3%), moderate atrophy (1.7%), metaplasia (1.7%), chronic gastritis (6.2%), and normal tissue (56%). The PGI/PGII ratio was significantly higher in H. pylori-negative patients (p < 0.01). PGII and PGI/PGII levels were lower in patients with metaplasia than in those with normal mucosa (p = 0.049 and p < 0.001, respectively). The PGI/PGII ratio best discriminated metaplasia and moderate atrophy (AUC 0.88 and 0.76, respectively). PGI and PGII alone showed poor discriminative ability, especially in mild atrophy (0.55 and 0.53, respectively) and chronic gastritis (0.55 and 0.53, respectively). The best cut-off to discriminate metaplasia was 3.25 U/mL (95.19% specificity, 83.33% sensitivity). Anti-H. pylori IgG and PG assessment (ABC method) was performed (group B, 2.0%; group A, 92.1%). The new cut-off more accurately identified patients with metaplasia requiring follow-up (group B, 5.4%). Assessment of anti-H. pylori IgG and PG is valuable in countries with a low prevalence of H. pylori infection.
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CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.