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Kong PF, Yan YH, Duan YT, Fang YT, Dou Y, Xu YH, Xu DZ. Comparative genomic analysis of Helicobacter pylori isolates from gastric cancer and gastritis in China. BMC Cancer 2025; 25:628. [PMID: 40197242 PMCID: PMC11978144 DOI: 10.1186/s12885-025-13493-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 01/10/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND This study aimed to explore and compare the genomic characteristics and pathogenicity of Helicobacter pylori (H. pylori) strains derived from the gastric cancer (GC) and gastritis in the Chinese population. METHODS We performed whole genome sequencing on 12 H. pylori strains obtained from GC and gastritis patients in China. Additionally, we retrieved sequencing data for 20 H. pylori strains from various regions worldwide from public databases to serve as reference genomes. An evolutionary tree was constructed based on comparative genomics, and we analyzed the differences in virulence factors (VFs) and gene functions. RESULTS In the GC strains, we identified 1,544 to 1,640 coding genes, with a total length ranging from 1,549,790 to 1,605,249 bp. In the gastritis strains, we found 1,552 to 1,668 coding genes, with a total length spanning from 1,552,426 to 1,665,981 bp. The average length of coding genes was approximately 1,594 (90.91%) for GC strains and 1,589 (90.81%) for gastritis strains. We observed a high degree of consistency in the VFs predicted for both cohorts; however, there was a significant difference in their cagA status. Clustering analysis showed significant core single nucleotide polymorphisms (SNPs) differences between GC and gastritis strains, but no major differences in homologous proteins or gene islands. Subsequent pan-genomic and Average Nucleotide Identity (ANI) analyses indicated high homology among GC, gastritis, and other reference H. pylori strains. Furthermore, gene function annotation results showed substantial similarity in gene functions between the H. pylori strains from GC and gastritis patients, with specific functions primarily concentrated in metabolic processes, transcription, and DNA repair. CONCLUSIONS H. pylori strains derived from GC and gastritis patients exhibit differences in virulence factors and SNPs, yet they demonstrate high genomic homology across other levels in the Chinese population.
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Affiliation(s)
- Peng-Fei Kong
- Department of Gastric Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China
| | - Yong-Hao Yan
- Department of Gastric Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China
| | - Yan-Tao Duan
- Department of Gastric Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China
| | - Yan-Tian Fang
- Department of Gastric Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China
| | - Yi Dou
- Department of Gastric Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China
| | - Yong-Hu Xu
- Department of Gastric Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China
| | - Da-Zhi Xu
- Department of Gastric Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.
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Shirani M, Pakzad R, Haddadi MH, Akrami S, Asadi A, Kazemian H, Moradi M, Kaviar VH, Zomorodi AR, Khoshnood S, Shafieian M, Tavasolian R, Heidary M, Saki M. The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis. BMC Infect Dis 2023; 23:543. [PMID: 37598157 PMCID: PMC10439572 DOI: 10.1186/s12879-023-08504-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 07/31/2023] [Indexed: 08/21/2023] Open
Abstract
BACKGROUND Helicobacter pylori is a gastrointestinal pathogen that infects around half of the world's population. H. pylori infection is the most severe known risk factor for gastric cancer (GC), which is the second highest cause of cancer-related deaths globally. We conducted a systematic review and meta-analysis to assess the global prevalence of GC in H. pylori-infected individuals. METHODS We performed a systematic search of the PubMed, Web of Science, and Embase databases for studies of the prevalence of GC in H. pylori-infected individuals published from 1 January 2011 to 20 April 2021. Metaprop package were used to calculate the pooled prevalence with 95% confidence interval. Random-effects model was applied to estimate the pooled prevalence. We also quantified it with the I2 index. Based on the Higgins classification approach, I2 values above 0.7 were determined as high heterogeneity. RESULTS Among 17,438 reports screened, we assessed 1053 full-text articles for eligibility; 149 were included in the final analysis, comprising data from 32 countries. The highest and lowest prevalence was observed in America (pooled prevalence: 18.06%; 95% CI: 16.48 - 19.63; I2: 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 - 13.12; I2: 88.39%). Among individual countries, Japan had the highest pooled prevalence of GC in H. pylori positive patients (Prevalence: 90.90%:95% CI: 83.61-95.14), whereas Sweden had the lowest prevalence (Prevalence: 0.07%; 95% CI: 0.06-0.09). The highest and lowest prevalence was observed in prospective case series (pooled prevalence: 23.13%; 95% CI: 20.41 - 25.85; I2: 97.70%) and retrospective cohort (pooled prevalence: 1.17%; 95% CI: 0.55 - 1.78; I 2: 0.10%). CONCLUSIONS H. pylori infection in GC patients varied between regions in this systematic review and meta-analysis. We observed that large amounts of GCs in developed countries are associated with H. pylori. Using these data, regional initiatives can be taken to prevent and eradicate H. pylori worldwide, thus reducing its complications.
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Affiliation(s)
- Maryam Shirani
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Reza Pakzad
- Department of Epidemiology, Faculty of Health, Ilam University Medical Sciences, Ilam, Iran
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Sousan Akrami
- Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Arezoo Asadi
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Kazemian
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Melika Moradi
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Vahab Hassan Kaviar
- Department of Medical Microbiology, Faculty of Medicine, Ilam University of Medical Science, Ilam, Iran
| | - Abolfazl Rafati Zomorodi
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saeed Khoshnood
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Mahnaz Shafieian
- Department of Midwifery, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran
| | - Ronia Tavasolian
- Department of Medicine, Faculty of Nutrition Science, University of Cheste, Chester, UK
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran.
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
| | - Morteza Saki
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Alkhaldi NK, Alghamdi WK, Alharbi MH, Almutairi AS, Alghamdi FT. The Association Between Oral Helicobacter pylori and Gastric Complications: A Comprehensive Review. Cureus 2022; 14:e24703. [PMID: 35663643 PMCID: PMC9162906 DOI: 10.7759/cureus.24703] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori (H. pylori) is linked to chronic gastritis, duodenal or gastric ulcers, and gastric cancer (GC). Because the oral cavity is the first component of the gastrointestinal tract (GIT) and the entrance point for H. pylori, it has been proposed as a possible reservoir of H. pylori. As a result, a putative oral-oral transmission pathway of H. pylori poses the possibility of whether personal contact, such as kissing or sharing a meal, might trigger H. pylori transmission. As a result, several investigations have been done on this issue using various approaches for detecting H. pylori in oral and stomach samples. Furthermore, the relationship between H. pylori and gastrointestinal disorders has yet to be studied. The evidence for the association between H. pylori and gastric diseases and their complications is still a controversial subject due to the existing literature in this review. The goal of this comprehensive review was to collect all available published articles and critically evaluate existing investigations looking into the relationship between oral H. pylori contamination and the danger of gastric complications. Few studies indicated an association between H. pylori and gastric diseases. Furthermore, more longitudinal randomized clinical studies to further investigate the association between H. pylori and gastric diseases are warranted.
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Affiliation(s)
- Njoud K Alkhaldi
- General Medicine and Surgery, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAU
| | - Waad K Alghamdi
- General Medicine and Surgery, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAU
| | - Maryam H Alharbi
- General Medicine and Surgery, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAU
| | - Albandri S Almutairi
- General Medicine and Surgery, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, SAU
| | - Faisal T Alghamdi
- Department of Oral Biology, Faculty of Dentistry, King Abdulaziz University, Jeddah, SAU
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Sirt3, 6, and 7 Genes Expression in Gastric Antral Epithelial Cells of Patients with Helicobacter pylori Infection. Curr Microbiol 2022; 79:114. [PMID: 35195783 DOI: 10.1007/s00284-022-02775-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 01/20/2022] [Indexed: 11/03/2022]
Abstract
Sirtuins, known as the intracellular acylation enzymes, play a major role in regulating the cell's physiological activities. The relevant studies have shown diversely sirtuin genes expression in various cancers in humans. This study has surveyed the transcription of sirt3, 6, and 7 genes in gastric antral epithelial cells (GAECs) of gastritis and gastric adenocarcinoma patients with and without Helicobacter pylori infection. First of all, a case-control study was conducted, including 50 and 53 gastric antral biopsy samples collected from gastritis and gastric adenocarcinoma patients with and without H. pylori infection referred to hospitals of Sanandaj City during 2018-2019. Total RNAs were extracted from biopsy samples, then cDNAs were synthesized by using TaKaRa kits. Quality essay of H. pylori virulence genes expression and relative quantitative essay of sirt3, 6, and 7 genes expressions in gastric antral biopsy samples were performed using the real-time RT-PCR method. The statistical analysis showed the significant correlations between H. pylori vacA s1m2 and sabA cDNAs with sirt3 geneś expression in GAECs (P < 0.05, 0.05 respectively). In addition, sirt6 gene's expression decreased along increasing age in gastric adenocarcinoma patients (P < 0.05). The samples of gastritis patients with gastric antral epithelial biopsy containing H. pylori hopQII, oipA, and sabB cDNA showed an increased amount of sirt7 genes expression (P < 0.05, 0.05, and 0.05 respectively). In conclusion, the H. pylori virulence genes expression and increasing age of patients showed the significant correlations with sirt3, 6, and 7 genes expressions in GAECs of gastric and gastric cancer patients.
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Hussein RA, Al-Ouqaili MT, Majeed YH. Detection of clarithromycin resistance and 23SrRNA point mutations in clinical isolates of Helicobacter pylori isolates: Phenotypic and molecular methods. Saudi J Biol Sci 2022; 29:513-520. [PMID: 35002447 PMCID: PMC8716959 DOI: 10.1016/j.sjbs.2021.09.024] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/05/2021] [Accepted: 09/08/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Peptic ulcer disease, chronic gastritis, and stomach cancer are all caused by H. pylori. The most notable drug for the treatment is the antibiotic clarithromycin, which is currently the drug of choice. H. pylori clarithromycin resistance has been associated with point mutations in 23srRNA, the most prominent of which are A2143 and A2144G. In H. pylori bacteria, methylase synthesis, macrolide-inactivating enzyme activity, and active efflux have all been found to be resistance mechanisms. The goal of the study is to determine how resistant H. pylori is to clarithromycin and what the minimum inhibitory concentration is for various antimicrobials. Furthermore, gastro-endoscopy will be performed on Iraqi patients to detect the presence of A2143G and A2144G point mutations in Helicobacter pylori infections, as diagnosed from the pyloric region and other anatomical regions. METHODS One hundred fifteen samples were collected from patients strongly suspected of H. pylori infection presented for upper gastrointestinal endoscopy at Ramadi Teaching Hospitals and Private Clinics for the period from January 2020 until February 2021. Specimens were cultured on brain heart infusion agar containing various antibiotics and were incubated at 37 °C under microaerophilic conditions. For identification of H. pylori, isolates of the biochemical tests and RT-PCR assay were applied. The Epsilometer test was used in the antibiotic susceptibility testing as dependent on the CLSI standard. The Restriction Fragment Length Polymorphism technique was used to determine point mutations. RESULTS In total, 55 (47.8%) Helicobacter pylori isolates were cultured from the 115 biopsy specimens, among which 16 (29.1%), 38 (69.1%), 20 (36.4%), and 40 (72.7%) revealed some degree of resistance to levofloxacin, clarithromycin, ciprofloxacin, and metronidazole, respectively. The frequency of A2144G and A2143 point mutations were 23 (60.5%) and 19 (50%), respectively. CONCLUSIONS According to our results, Helicobacter pylori showed high resistance to clarithromycin. Our results demonstrate the requirement for antibiotic susceptibility testing and molecular methods in selecting drug regimens.
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Affiliation(s)
- Rawaa A. Hussein
- Department of Clinical Laboratory Sciences, College of Pharmacy, University of Anbar, Al-Anbar Governorate, Ramadi, Iraq
| | - Mushtak T.S. Al-Ouqaili
- Department of Microbiology, College of Medicine, University of Anbar, Al-Anbar Governorate, Ramadi, Iraq
| | - Yasin H. Majeed
- Department of Internal Medicine, College of Medicine, University of Anbar, Al-Anbar Governorate, Ramadi, Iraq
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Mirbagheri SZ, Bakhtiari R, Fakhre Yaseri H, Rahimi Foroushani A, Eshraghi SS, Alebouyeh M. Transcriptional alteration of genes linked to gastritis concerning Helicobacter pylori infection status and its virulence factors. Mol Biol Rep 2021; 48:6481-6489. [PMID: 34427890 DOI: 10.1007/s11033-021-06654-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 08/16/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Helicobacter pylori infection and heterogeneity in its pathogenesis could describe diversity in the expression of inflammatory genes in the gastric tissue. We aimed to investigate transcriptional alteration of genes linked to gastritis concerning the H. pylori infection status and its virulence factors. METHODS AND RESULTS Biopsy samples of 12 infected and 12 non-infected patients with H. pylori that showed moderate chronic gastritis were selected for transcriptional analysis. Genotyping of H. pylori strains was done using PCR and relative expression of inflammatory genes was compared between the infected and non-infected patients using relative quantitative real-time PCR. Positive correlations between transcriptional changes of IL8 with TNF-α and Noxo1 in the infected and TNF-α with Noxo1, MMP7, and Atp4A in the non-infected patients were detected. Six distinct genotypes of H. pylori were detected that showed no correlation with gender, ethnicity, age, endoscopic findings, and transcriptional levels of host genes. Irrespective of the characterized genotypes, our results showed overexpression of TNF-α, MMP7, Noxo1, and ATP4A in the infected and IL-8, Noxo1, and ATP4A in the non-infected patients. CONCLUSIONS A complexity in transcription of genes respective to the characterized H. pylori genotypes in the infected patients was detected in our study. The observed difference in co-regulation of genes linked to gastritis in the infected and non-infected patients proposed involvement of different regulatory pathways in the inflammation of the gastric tissue in the studied groups.
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Affiliation(s)
- Seyedeh Zohre Mirbagheri
- Department of Pathobiology, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Ronak Bakhtiari
- Department of Pathobiology, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hashem Fakhre Yaseri
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.,Gastroenterology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Abbas Rahimi Foroushani
- Department of Epidemiology and Biostatistics, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyyed Saeed Eshraghi
- Department of Pathobiology, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Alebouyeh
- Pediatric Infections Research Centre, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Li Y, Lin R, Jin Y, Jin S, Chen B, Wu X. Genotyping Helicobacter pylori antibiotic resistance - and virulence-associated genes in patients with gastric cancer in Wenzhou, China. Arab J Gastroenterol 2021; 22:267-271. [PMID: 34120851 DOI: 10.1016/j.ajg.2021.05.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/02/2021] [Accepted: 05/31/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS Helicobacter pylori infection affects approximately 50% of the global population and has become a serious health concern related to gastric cancer, gastritis, and peptic ulcers. This organism acquires drug resistance through gene mutations, and its increasing resistance to antibiotics has severely influenced the effectiveness of eradication efforts. Therefore, we designed this study to determine the prevalence of H. pylori virulence- (cagA and vacA) and antibiotic resistance - associated genotypes in patients with gastric cancer infected with H. pylori in Whenzhou, China. PATIENTS AND METHODS We used polymerase chain reaction (PCR) to confirm H. pylori in cancerous and paracancerous tissue specimens from 225 patients. Then we tested the prevalence of virulence- and antibiotic resistance - associated genotypes in H. pylori using a PCR-based DNA-sequencing assay. RESULTS We observed H. pylori DNA in 222 of the 225 patients and found the most prevalent virulence-associated genotypes in cagA+ (97.75%) and vacAs1m1 (93.25%). Metronidazole resistance - associated gene mutation was G616A in rdxA; levofloxacin resistance - associated gene mutations were N87K, N87I, and D91G in gyrA; clarithromycin resistance - associated gene mutations were A2143G and A2142G in 23SrRNA; and amoxicillin resistance - associated gene mutation was T556S in pbp1. The most prevalent mutation related to antibiotic resistance was present in rdxA (97.30%), followed by gyrA (41.44%) and 23SrRNA (16.67%); the least prevalent was in pbp1 (2.25%). We observed single-gene mutations in 102 patients (45.95%) and found mutations in multiple genes (≥2 genes) in 116 patients (52.25%). CONCLUSION Patients with gastric cancer in Wenzhou, China, have high incidence infection caused by H. pylori with high-toxicity virulence genotypes. The frequency of gene mutations associated with metronidazole, levofloxacin, and clarithromycin resistances was high and that associated with amoxicillin resistance was relatively low. The mutation patterns were diverse, and the rates of multiple gene mutations were high.
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Affiliation(s)
- Yonglin Li
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Rixu Lin
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yin Jin
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Shuqing Jin
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Bicheng Chen
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
| | - Xiuling Wu
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
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Keikha M, Karbalaei M. EPIYA motifs of Helicobacter pylori cagA genotypes and gastrointestinal diseases in the Iranian population: a systematic review and meta-analysis. New Microbes New Infect 2021; 41:100865. [PMID: 33912350 PMCID: PMC8066700 DOI: 10.1016/j.nmni.2021.100865] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/01/2021] [Accepted: 03/07/2021] [Indexed: 02/08/2023] Open
Abstract
Helicobacter pylori is one of the best risk factors for gastric cancer. Recent studies have examined the relationship between virulence factors, in particular CagA toxin, and the development of gastrointestinal diseases. According to the literature, there is a significant relationship between the polymorphism of cagA-EPIYA motifs and progression to severe clinical outcomes. The main goal of our study was to determine the possible association between cagA genotypes and the risk of severe clinical outcomes in the Iranian population. We investigated these ambiguities using a comprehensive meta-analysis study, in which we evaluated data from 1762 Iranian patients for a potential correlation between all cagA gene genotypes and gastrointestinal diseases. According to statistical analysis, the frequencies of cagA genotypes including ABC, ABCC, AB and ABCCC in the Iranian population were estimated at 80.18%, 22.81%, 5.52% and 2.76%, respectively; the ABD genotype was not detected in these PCR-based studies. There was a significant relationship between cagA genotypes ABCC and ABCCC and severe clinical outcomes of infection such as peptic ulcer and gastric cancer. Overall, it can be concluded that there is a positive correlation with the number of copies of EPIYA-C and the increase of gastric cancer. Therefore, according to our results, it seems that the EPIYA-ABCCC motif has a strong positive relationship with gastric cancer in the Iranian population.
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Affiliation(s)
- M. Keikha
- Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - M. Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
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Horiuchi S, Nakano R, Nakano A, Hishiya N, Uno K, Suzuki Y, Kakuta N, Kakuta R, Tsubaki K, Jojima N, Yano H. Prevalence of Helicobacter pylori among residents and their environments in the Nara prefecture, Japan. J Infect Public Health 2021; 14:271-275. [PMID: 33508684 DOI: 10.1016/j.jiph.2020.11.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 11/12/2020] [Accepted: 11/19/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Chronic infection with Helicobacter pylori, specifically cagA-positive strains, is associated with gastric cancer. Thus, measures to prevent H. pylori infection are required. This study was conducted to clarify the prevalence of H. pylori in the community to identify the infection source and comprehensively assess the risk of H. pylori infection. METHODS We collected 90 human faecal samples and 73 environmental samples (water, vegetable, and animal faecal samples) from the residents in an area with a high incidence of gastric cancer in Japan. Polymerase chain reaction assay was performed to detect the glmM housekeeping gene and the cagA virulence gene of H. pylori. A questionnaire survey was conducted, and the responses were analyzed statistically. RESULTS The glmM gene was detected in 18 of 90 (20%) faecal samples obtained from residents; among them, the cagA gene was detected in 33.3% (6/18), and in all who had undergone eradication therapy. H. pylori was not detected in environmental samples. However, contact with dogs (OR 3.89, 95% CI 1.15-13.15, P < 0.05) was associated with higher odds for glmM gene positivity in the questionnaire survey. CONCLUSIONS The prevalence of H. pylori and cagA-positive strains among the residents was low. However, the study results suggest a correlation between recurrent infection and cagA-positive H. pylori strains. Although H. pylori genes were not detected in living environments, an association between contact with dogs and a glmM positive status was revealed. Further investigations targeting community-dwelling healthy people and their living environments would be required for H. pylori infection control.
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Affiliation(s)
- Saori Horiuchi
- Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan; Department of Public Health Nursing, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan
| | - Ryuichi Nakano
- Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan.
| | - Akiyo Nakano
- Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan
| | - Naokuni Hishiya
- Department of Infectious Diseases, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo, Yoshino-gun, Nara 638-8551, Japan
| | - Kenji Uno
- Department of Infectious Diseases, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo, Yoshino-gun, Nara 638-8551, Japan
| | - Yuki Suzuki
- Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan
| | - Naoki Kakuta
- Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan
| | - Risako Kakuta
- Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
| | - Kohsuke Tsubaki
- Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan
| | - Noriko Jojima
- Department of Public Health Nursing, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan
| | - Hisakazu Yano
- Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara 634-8521, Japan
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Kamarehei F, Taheri M, Mohammadi Y, Shokoohizadeh L, Alikhani MY. Prevalence of Helicobacter pylori virulence genes among Iranian infected patients: a systematic review and meta-analysis. REVIEWS IN MEDICAL MICROBIOLOGY 2020; 31:191-200. [DOI: 10.1097/mrm.0000000000000207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Introduction:
Helicobacter pylori infection as the worldwide problem is related to many gastrointestinal disorders. Because of antithesis results among different articles; we systematically reviewed articles about the prevalence of H. pylori virulence factors among different diseases (gastritis, gastric cancer, nonulcer disease, peptic ulcer disease, duodenal ulcer) in different regions of Iran.
Methods:
We used the Preferred Reporting Items for Systematic Review and Meta-Analysis statement for reporting systematic review and meta-analysis of this study in national and international databases. We searched the cagA, vacA, oipA, babA, iceA, dupA prevalence among infected patients in Iran. We used Newcastle--Ottawa quality for assessing the quality of studies in meta-analyses. Due to significant heterogeneity of the results, random effects model to calculate pooled prevalence estimates with 95% confidence intervals, weighted by study size.
Results:
Among 1106 reports screened, 28 related articles were eligible for meta-analysis. The pooled prevalence (95% confidence interval) of cagA, vacA, oipA, babA, iceA1, iceA2, dupA were estimated as 62% (21--95), 71.2% (38–82), 71% (13–99), 61.6% (3–96), 36.2% (12–90), 26.2% (13–37), 40.8% (12–55), respectively.
Discussion:
The frequency of virulence factor genes among H. pylori strains isolated in Iranian patients to be more frequently associated with the gastrointestinal disease compared with the other countries and these data can be considered in development of eradication strategies.
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Affiliation(s)
| | | | - Younes Mohammadi
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
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11
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Keikha M, Ali-Hassanzadeh M, Karbalaei M. Association of Helicobacter pylori vacA genotypes and peptic ulcer in Iranian population: a systematic review and meta-analysis. BMC Gastroenterol 2020; 20:266. [PMID: 32795257 PMCID: PMC7427722 DOI: 10.1186/s12876-020-01406-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 07/29/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Helicobacter pylori is accounted as the most etiologic agent for digestive disorders, in particular, the most important of them i.e. peptic ulcer and gastric cancer. In the recent years, association of vacA genotypes and gastrointestinal disorders has attracted a lot of attention. In present study, we assessed the correlation between vacA genotypes (s1, s2, m1, m2, s1m1, s1m2, s2m1 and s2m2) and development to peptic ulcer in Iranian population. METHODS In our study, first, 24 original articles containing of information of 3328 patients were evaluated. Statistical analysis was done by Comprehensive Meta-Analysis version 2.0 software (Biostat, Englewood, NJ, USA). In this regards, we used from fixed-effects model for analysis of data with low heterogeneity, while for analysis of data with high heterogeneity (I2 statistic index > 25%, Cochrane Q statistic p value < 0.05), random-effects model was used. RESULTS Abundance of each of s1, s2, m1, m2, s1m1, s1m2, s2m1, and s2m2 was estimated 36.24, 28.32, 42.90 29.86, 27.88, 32.34, 15.70, and 25.94%, respectively. According to the results, the m1, s1, and s1m2 genotypes were among the most prevalent genotypes among the Iranian patients, whereas, s2m1 genotype had the lowest frequency. CONCLUSIONS Overall, 24 articles (total participants = 3328) were included in this comprehensive analysis. H. pylori infection rate were 90.26% in these cases, so that 33.65% of whom had peptic ulcer. Moreover, the abundance of each vacA genotypes including s1, s2, m1, m2, s1m1, s1m2, s2m1, and s2m2 was estimated as 36.24, 28.32, 42.90 29.86, 27.88, 32.34, 15.70, and 25.94% respectively. We demonstrated that there is a significant relationship between infection of stomach with m1, s1m1, and s2m1 genotypes and development to peptic ulcer disease.
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Affiliation(s)
- Masoud Keikha
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Ali-Hassanzadeh
- Department of Immunology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran.
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12
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Zhao Q, Song C, Wang K, Li D, Yang Y, Liu D, Wang L, Zhou N, Xie Y. Prevalence of Helicobacter pylori babA, oipA, sabA, and homB genes in isolates from Chinese patients with different gastroduodenal diseases. Med Microbiol Immunol 2020; 209:565-577. [PMID: 32219508 DOI: 10.1007/s00430-020-00666-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/16/2020] [Indexed: 02/06/2023]
Abstract
Disease outcome is associated with virulence factors of Helicobacter pylori (H. pylori), which are partially attributed to the outer membrane protein (OMP). This study aimed to investigate the correlation between the four OMP genes (babA, oipA, sabA, and homB) and gastroduodenal diseases. One hundred and seventy-seven H. pylori strains were isolated from Chinese patients with different gastroduodenal diseases (49 chronic gastritis, 19 gastric ulcer, 33 gastric cancer, and 76 duodenal ulcer), 94 of which contained pathological information (41 superficial gastritis, 24 intestinal hyperplasia, and 29 gastric adenocarcinoma). The full-length amplification of babA, oipA, sabA, and homB genes was acquired and sequenced. Then, the genetic polymorphism was analyzed to compare with the reference strains from the GenBank database. Functional status and cluster analysis were also performed to evaluate the impact of genetic polymorphism on disease outcome. The prevalence of babA, oipA, sabA, and homB genes were 91.5%, 100%, 94.0%, and 95.5%, respectively. The four OMP genes were characterized by genetic polymorphism and in the status of positive selection (Ka/Ks> 1). The proportion of strains with functional status on for oipA and sabA gene was 100% and 76.2%, respectively. The sequences of four OMP genes were mainly clustered together with the East Asian references. The four OMP genes were not different in patients with gastroduodenal diseases and pathologic changes (P > 0.05). H. pylori babA, oipA, sabA, and homB genes were common in the Chinese populations, but did not seem to be involved in the development of gastroduodenal diseases.
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Affiliation(s)
- Qiaoyun Zhao
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, 330006, Jiangxi, China.,Microbiology Laboratory, Gastroenterology Institute of Jiangxi Province, Nanchang, 330006, Jiangxi, China.,Gastroenterology Research Center, Key Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, 330006, Jiangxi, China
| | - Conghua Song
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, 330006, Jiangxi, China.,Microbiology Laboratory, Gastroenterology Institute of Jiangxi Province, Nanchang, 330006, Jiangxi, China.,Gastroenterology Research Center, Key Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, 330006, Jiangxi, China.,Department of Gastroenterology, Affiliated Hospital of Putian University, Putian, 351100, Fujian, China
| | - Ke Wang
- Laboratory of Biochemistry and Molecular Biology, Jiangxi Institute of Medical Sciences, Nanchang, 330006, Jiangxi, China
| | - Donghong Li
- Laboratory of Biochemistry and Molecular Biology, Jiangxi Institute of Medical Sciences, Nanchang, 330006, Jiangxi, China
| | - Yang Yang
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, 330006, Jiangxi, China.,Microbiology Laboratory, Gastroenterology Institute of Jiangxi Province, Nanchang, 330006, Jiangxi, China.,Gastroenterology Research Center, Key Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, 330006, Jiangxi, China
| | - Dongsheng Liu
- Microbiology Laboratory, Gastroenterology Institute of Jiangxi Province, Nanchang, 330006, Jiangxi, China.,Gastroenterology Research Center, Key Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, 330006, Jiangxi, China
| | - Le Wang
- Microbiology Laboratory, Gastroenterology Institute of Jiangxi Province, Nanchang, 330006, Jiangxi, China.,Gastroenterology Research Center, Key Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, 330006, Jiangxi, China
| | - Nanjin Zhou
- Laboratory of Biochemistry and Molecular Biology, Jiangxi Institute of Medical Sciences, Nanchang, 330006, Jiangxi, China
| | - Yong Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, 330006, Jiangxi, China. .,Microbiology Laboratory, Gastroenterology Institute of Jiangxi Province, Nanchang, 330006, Jiangxi, China. .,Gastroenterology Research Center, Key Laboratory of Digestive Diseases of Jiangxi Province, Nanchang, 330006, Jiangxi, China.
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13
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Amin M, Shayesteh AA, Serajian A. Concurrent detection of cagA, vacA, sodB and hsp60 virulence genes and their relationship with clinical outcomes of disease in Helicobacter pylori isolated strains of southwest of Iran. IRANIAN JOURNAL OF MICROBIOLOGY 2019; 11:198-205. [PMID: 31523402 PMCID: PMC6711871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
BACKGROUND AND OBJECTIVES Helicobacter pylori is a Gram-negative spiral-shaped bacterium that contaminates more than half of the world's inhabitants, and infection with this bacterium is associated with some gastric disorders. Also, 5% to 10% of H. pylori genes are specific to this bacterium and many bacterial virulence factors fall into this group. The cagA, vacA, sodB and hsp60 are among important virulence factors of H. pylori. MATERIALS AND METHODS A gastric biopsy specimen was taken from 341 gastric patients and cultivated on a Colombia agar plate, containing various antibiotics, such as vancomycin, amphotericin B, and trimethoprim & polymyxin B, and incubated for 3 to 10 days under microaerophilic conditions at 37°C. PCR was used to detect the ureC, cagA, vacA, sodB and hsp60 genes. RESULTS In this study, 131 isolates were identified as H. pylori. The prevalence of cagA, vacA, sodB and hsp60 were 74%, 100%, 92.4% and 96.2%, respectively. The correlation between the clinical forms of the disease and the virulence genes were analyzed by statistical tests and no significant correlation was found. CONCLUSION The obtained results are similar to some studies conducted in different parts of the world and is different in other cases. This discrepancy is due to the difference in the type of gastric disorders, sample size and methodology.
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Affiliation(s)
- Mansour Amin
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Akbar Shayesteh
- Research Center for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Amirarsalan Serajian
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,Corresponding author: Amirarsalan Serajian, Ph.D, Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Tel: +986133330074, Fax: +986133720160,
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14
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Assessment of Metronidazole and Clarithromycin Resistance Among Helicobacter pylori Isolates of Ahvaz (Southwest of Iran) During 2015 - 2016 by Phenotypic and Molecular Methods. Jundishapur J Microbiol 2019. [DOI: 10.5812/jjm.80156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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15
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Heidarian F, Alebouyeh M, Shahrokh S, Balaii H, Zali MR. Altered fecal bacterial composition correlates with disease activity in inflammatory bowel disease and the extent of IL8 induction. Curr Res Transl Med 2019; 67:41-50. [PMID: 30685379 DOI: 10.1016/j.retram.2019.01.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 01/10/2019] [Accepted: 01/15/2019] [Indexed: 12/26/2022]
Abstract
PURPOSE OF THE STUDY In this study we investigated the presence and relative abundance of important genera of the gut microbiota in IBD patients and their role in induction of IL8 in a cell culture model. PATIENTS AND METHODS Stool samples of IBD patients and healthy controls were collected and relative diversity of thirteen bacterial families was measured using quantitative real-time PCR assay. Moreover, filtrate of the stool samples was used for treatment of HT-29 cell line to analyze involvement of diversity of the fecal bacterial communities in the extent of IL8 induction. RESULTS Bacteroides, Faecalibacterium prausnitzii, Prevotella spp., and Methanobrevibacterium were significantly less abundant in IBD patients (UC, N = 22; CD, N = 7) compared with control group (N = 29). Increase in relative amounts of Haemophilus, Streptococcus spp., and H. pylori were detected in IBD patients, which was not statistically significant. Relative decrease in amount of Bacteroides spp., Faecalibacterium prausnitzii, and Prevotella spp. were found in UC patients with disease activity score greater than 4; however, higher levels of Streptococcus and Haemophilus were detected in the patients who were at flares. A relationship between the reduction of Haemophilus spp. and higher BMI was shown in IBD patients. Expression of IL8 was significantly higher in the treated cells by the fecal inoculates of IBD patients. Increase in relative amounts of Enterobacteriacea showed a correlation with the higher level of IL8 induction in both groups. CONCLUSIONS These results showed that changes in the fecal microbiota composition could affect disease activity, BMI, and IL8 induction.
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Affiliation(s)
- Farnaz Heidarian
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Masoud Alebouyeh
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Hedieh Balaii
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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16
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Mojtahedi A, Fakhrieh Asl S, Aminian K, Pourvahedi M, Saadat F, Fallah Karkan M. The association between iceA and vacA allelic gene variations of Helicobacter pylori strains and gastric disorders. GENE REPORTS 2018. [DOI: 10.1016/j.genrep.2018.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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17
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Vaziri F, Tarashi S, Fateh A, Siadat SD. New insights of Helicobacter pylori host-pathogen interactions: The triangle of virulence factors, epigenetic modifications and non-coding RNAs. World J Clin Cases 2018; 6:64-73. [PMID: 29774218 PMCID: PMC5955730 DOI: 10.12998/wjcc.v6.i5.64] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 02/09/2018] [Accepted: 03/07/2018] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, MicroRNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.
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Affiliation(s)
- Farzam Vaziri
- Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
| | - Samira Tarashi
- Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
| | - Abolfazl Fateh
- Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
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18
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Lee SH, Lee JJ, Kwon Y, Kim JH, Sohn JH. Clinical Implications of Associations between Headache and Gastrointestinal Disorders: A Study Using the Hallym Smart Clinical Data Warehouse. Front Neurol 2017; 8:526. [PMID: 29042857 PMCID: PMC5632350 DOI: 10.3389/fneur.2017.00526] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Accepted: 09/21/2017] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND The brain and gastrointestinal (GI) tract are strongly connected via neural, endocrine, and immune pathways. Previous studies suggest that headaches, especially migraines, may be associated with various GI disorders. However, upper GI endoscopy in migraineurs has shown a low prevalence of abnormal findings. Also, the majority of studies have not demonstrated an association between Helicobacter pylori (HP) infection and migraine, although a pathogenic role for HP infection in migraines has been suggested. Further knowledge concerning the relation between headaches and GI disorders is important as it may have therapeutic consequences. Thus, we sought to investigate possible associations between GI disorders and common primary headaches, such as migraines and tension-type headaches (TTH), using the Smart Clinical Data Warehouse (CDW) over a period of 10 years. METHODS We retrospectively investigated clinical data using a clinical data analytic solution called the Smart CDW from 2006 to 2016. In patients with migraines and TTH who visited a gastroenterology center, GI disorder diagnosis, upper GI endoscopy findings, and results of HP infection were collected and compared to clinical data from controls, who had health checkups without headache. The time interval between headache diagnosis and an examination at a gastroenterology center did not exceed 1 year. RESULTS Patients were age- and sex-matched and eligible cases were included in the migraine (n = 168), the TTH (n = 168), and the control group (n = 336). Among the GI disorders diagnosed by gastroenterologists, gastroesophageal reflux disorder was more prevalent in the migraine group, whereas gastric ulcers were more common in the migraine and TTH groups compared with controls (p < 0.0001). With regard to endoscopic findings, there were high numbers of erosive gastritis and chronic superficial gastritis cases in the migraine and TTH groups, respectively, and the severity of gastritis was significantly higher in patients with TTH compared with controls (p < 0.001). However, no differences were observed in the prevalence of HP infection between the groups. CONCLUSION The observed association in this study may suggest that primary headache sufferers who experience migraines or TTH are more prone to GI disorders, which may have various clinical implications. Further research concerning the etiology of the association between headaches and GI disorders is warranted.
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Affiliation(s)
- Sang-Hwa Lee
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, South Korea
| | - Jae-June Lee
- Department of Anesthesiology and Pain Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, South Korea
| | - Youngsuk Kwon
- Department of Anesthesiology and Pain Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, South Korea
| | - Jong-Ho Kim
- Department of Anesthesiology and Pain Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, South Korea
| | - Jong-Hee Sohn
- Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, South Korea
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19
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Gharibi S, Falsafi T, Alebouyeh M, Farzi N, Vaziri F, Zali MR. Relationship between histopathological status of the Helicobacter pylori infected patients and proteases of H. pylori in isolates carrying diverse virulence genotypes. Microb Pathog 2017; 110:100-106. [PMID: 28629725 DOI: 10.1016/j.micpath.2017.06.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2017] [Revised: 06/09/2017] [Accepted: 06/15/2017] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori is the main cause of several gastroduodenal diseases in Humans. Among various virulence factors of H. pylori, proteases may also be involved in its pathogenicity. In this study, relationship between proteolytic activity of H. pylori strains and histopathological changes of the stomach was investigated in the patients infected with strains carrying diverse virulence factors. H. pylori strains were isolated from the biopsies of 116 patients who referred to hospital for their gastroduodenal disorders, in Tehran, Iran. Biopsies were sent to microbiology and pathology laboratories for further analysis. All the suspected grown colonies were characterized by both biochemical tests and polymerase chain reaction (PCR). Presence of seven protease genes, htrA, clpP, hp0169, hp1012, hp0382, hp1350 and hp1435, and distinct allelic variants of H. pylori virulence factors, cagA, vacA, iceA, babA2 and sabA, were analyzed in each strain. Protease activity of the strains was assessed using spectrophotometric assay. Furthermore, association between diversity in protease genes and virulence genes, protease activity, as well as pathological changes was estimated statistically. Proteases genes, htrA, clpP, hp0169, hp1012, hp0382, hp1350, hp1435, were detected among 100%, 100%, 98%, 98%, 98%, 98%, and 8% of fifty H. pylori strains isolated from the patients, respectively. Status of cagA, vacA s1, vacA s2, vacA m1, vacA m2, iceA1, iceA2, babA2 and sabA genes in isolates were 64%, 68%, 30%, 26%, 74%, 48%, 52%, 100%, and 96%, respectively. Predominant (84%) combined status for protease genes was: htrA/clpP/hp0169/hp1012/hp0382/hP1350/hp1435, while the prevalent combined status (16%) for virulence genes was: cagA+/vacA s1m2/iceA1+/sabA+/babA2+. Although most of the strains (91.4%) presented moderate protease activity in vitro, lowest activity was measured in strains isolated from the patients with chronic gastritis (4.25%). Present study provide the new data on diversity of protease genes in H. pylori, as well as the proteolytic activity of these genes in H. pylori strains from the sick patients. Presence of significant association between lower protease activity of the strains and mildness of the pathological changes propose involvement of these proteases in the pathogenesis of H. pylori in vivo.
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Affiliation(s)
- Somayyeh Gharibi
- Department of Microbiology, Faculty of Biological Science, Alzahra University, Tehran, Iran
| | - Tahereh Falsafi
- Department of Microbiology, Faculty of Biological Science, Alzahra University, Tehran, Iran.
| | - Masoud Alebouyeh
- Foodborne and Waterborne Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Nastaran Farzi
- Foodborne and Waterborne Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzam Vaziri
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, Iran
| | - Mohamad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Jalilian S, Alvandi A, Jouybari TA, Pajavand H, Abiri R. Lack of association association between the presence of dupA and babA 2 genes in Helicobacter pylori and gastroduodenal disorders. MOLECULAR GENETICS MICROBIOLOGY AND VIROLOGY 2017. [DOI: 10.3103/s0891416817010074] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Sohrabi M, Khashei R, Alizadeh M, Asl MKH, Nejati MA, Dara M, Bazargani A. Low Rate of babA2 Genotype among Iranian Helicobacter pylori Clinical Isolates. J Clin Diagn Res 2017; 11:DC32-DC36. [PMID: 28892894 DOI: 10.7860/jcdr/2017/24810.10277] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 05/04/2017] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The Blood Group Antigen-Binding Adhesion (babA), Outer Inflammatory Protein (oipA) and Sialic Acid-Binding Adhesin (sabA) as outer membrane proteins involved in Helicobacter pylori adherence to gastric mucosa have been suggested to have a role in the pathogenesis. AIM To investigate the frequency of H. pylori isolates babA2, oipA and sabA genes in Iranian dyspeptic patients. MATERIALS AND METHODS DNAs were extracted from H. pylori -positive cultures taken from 100 different dyspeptic patients. Genotyping was performed by Polymerase Chain Reaction (PCR), using the specific primers for babA2, oipA and sabA genes. Chi square test was used to investigate association between variables, p<0.05 was considered statistically significant. RESULTS All (100%) isolates possessed oipA and sabA genotypes, whereas babA2 was detected in 22% of isolates. There was no significant relationship between presence of genes with clinical outcome. The combined genotype oipA +/sabA +/ babA2- was correlated with gastritis. The rate of babA2 genotype in our isolates was lower than other Iranian reports. CONCLUSION Frequency of babA2 genotype among H. pylori isolates from Southwest of Iran is considerably less than other regions of Iran. Due to heterogeneity of H. pylori strains in different geographic regions, further work will be needed to understand the role of these virulence genes in H. pylori pathogenesis and their possible association with disease outcome.
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Affiliation(s)
- Maryam Sohrabi
- Student, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Khashei
- Assistant Professor, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahvash Alizadeh
- Assistant Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad-Kazem Hosseini Asl
- Associate Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad-Ali Nejati
- Assistant Professor, Department of Internal Medicine, Gastroenterology Ward, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahintaj Dara
- Ph.D Student, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abdollah Bazargani
- Associate Professor, Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Safaralizadeh R, Dastmalchi N, Hosseinpourfeizi M, Latifi-Navid S. Helicobacter pylori virulence factors in relation to gastrointestinal diseases in Iran. Microb Pathog 2017; 105:211-217. [DOI: 10.1016/j.micpath.2017.02.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Revised: 02/15/2017] [Accepted: 02/17/2017] [Indexed: 02/08/2023]
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Zhang SH, Xie Y, Li BM, Liu DS, Wan SH, Luo LJ, Xiao ZJ, Li H, Yi LJ, Zhou J, Zhu X. [Prevalence of Helicobacter pylori cagA, vacA, and iceA genotypes in children with gastroduodenal diseases]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2016; 18:618-24. [PMID: 27412545 PMCID: PMC7388991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 05/17/2016] [Indexed: 08/01/2024]
Abstract
OBJECTIVE To investigate the prevalence of cagA, vacA, and iceA genotypes in the isolated strains of Helicobacter pylori (H.pylori) from children with gastroduodenal diseases in Jiangxi, China, as well as the association between cagA, vacA, and iceA genotypes and the type of gastroduodenal diseases. METHODS The samples of gastric antral mucosa were collected from 316 children with gastroduodenal diseases in Jiangxi, and a total of 107 strains of H.pylori were isolated. The genomic DNA of these strains was extracted, and PCR was used to determine the ureA, cagA, vacA, and iceA genotypes. RESULTS Of all the 107 isolated strains of H.pylori, the detection rates of ureA and cagA genes were 100% (107/107) and 94.4% (101/107) respectively. The overall detection rate of vacA gene was 100% (107/107), and the detection rates of vacAs1a, vacAs1c, vacAm1, and vacAm2 genes were 74.8% (80/107), 25.2% (27/107), 29.9% (32/107), and 69.2% (74/107) respectively, with both vacAm1 and vacAm2 genes detected in 0.9% (1/107) of all H.pylori strains. In the chimera of vacA gene, the detection rates of vacAs1a/m1, vacAs1a/m2, vacAs1c/m1, and vacAs1c/m2 genes were 26.2% (28/107), 51.4% (55/107), 3.7% (4/107), and 17.8% (19/107) respectively (P<0.001). The detection rates of iceA1 and iceA2 genes were 79.4% (85/107) and 9.3% (10/107), respectively (P<0.001), and both iceA1 and iceA2 genes were detected in 7.5% (8/107) of all strains. The detection rates of the genotypes of H.pylori showed no significant differences between the peptic ulcer, chronic gastritis, and duodenal bulbar inflammation groups (P>0.05). CONCLUSIONS The dominant genotypes of H.pylori are cagA, vacAs1a/m2, and iceA1, and there are mixed infections with H.pylori strains of different genotypes in children with gastroduodenal disease from Jiangxi, China. The genotypes of H.pylori are not associated with the type of gastroduodenal disease.
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Affiliation(s)
- Shuang-Hong Zhang
- Department of Digestive Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
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Zhang SH, Xie Y, Li BM, Liu DS, Wan SH, Luo LJ, Xiao ZJ, Li H, Yi LJ, Zhou J, Zhu X. [Prevalence of Helicobacter pylori cagA, vacA, and iceA genotypes in children with gastroduodenal diseases]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2016; 18:618-624. [PMID: 27412545 PMCID: PMC7388991 DOI: 10.7499/j.issn.1008-8830.2016.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 05/17/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVE To investigate the prevalence of cagA, vacA, and iceA genotypes in the isolated strains of Helicobacter pylori (H.pylori) from children with gastroduodenal diseases in Jiangxi, China, as well as the association between cagA, vacA, and iceA genotypes and the type of gastroduodenal diseases. METHODS The samples of gastric antral mucosa were collected from 316 children with gastroduodenal diseases in Jiangxi, and a total of 107 strains of H.pylori were isolated. The genomic DNA of these strains was extracted, and PCR was used to determine the ureA, cagA, vacA, and iceA genotypes. RESULTS Of all the 107 isolated strains of H.pylori, the detection rates of ureA and cagA genes were 100% (107/107) and 94.4% (101/107) respectively. The overall detection rate of vacA gene was 100% (107/107), and the detection rates of vacAs1a, vacAs1c, vacAm1, and vacAm2 genes were 74.8% (80/107), 25.2% (27/107), 29.9% (32/107), and 69.2% (74/107) respectively, with both vacAm1 and vacAm2 genes detected in 0.9% (1/107) of all H.pylori strains. In the chimera of vacA gene, the detection rates of vacAs1a/m1, vacAs1a/m2, vacAs1c/m1, and vacAs1c/m2 genes were 26.2% (28/107), 51.4% (55/107), 3.7% (4/107), and 17.8% (19/107) respectively (P<0.001). The detection rates of iceA1 and iceA2 genes were 79.4% (85/107) and 9.3% (10/107), respectively (P<0.001), and both iceA1 and iceA2 genes were detected in 7.5% (8/107) of all strains. The detection rates of the genotypes of H.pylori showed no significant differences between the peptic ulcer, chronic gastritis, and duodenal bulbar inflammation groups (P>0.05). CONCLUSIONS The dominant genotypes of H.pylori are cagA, vacAs1a/m2, and iceA1, and there are mixed infections with H.pylori strains of different genotypes in children with gastroduodenal disease from Jiangxi, China. The genotypes of H.pylori are not associated with the type of gastroduodenal disease.
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Affiliation(s)
- Shuang-Hong Zhang
- Department of Digestive Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
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Abdi E, Latifi-Navid S, Latifi-Navid H, Safarnejad B. Helicobacter pylori vacuolating cytotoxin genotypes and preneoplastic lesions or gastric cancer risk: a meta-analysis. J Gastroenterol Hepatol 2016; 31:734-44. [PMID: 26648346 DOI: 10.1111/jgh.13256] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2015] [Accepted: 11/21/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Disease progression to gastric cancer (GC) occurs in only a small proportion of Helicobacter pylori (H. pylori) infected patients. The bacterium vacuolating cytotoxin A (vacA) gene polymorphisms may determine the clinical consequences. We examined the strength of this association in adult-infected populations and modeled the impact of mean age-standardized incidence rates (ASRs) of GC as a hypothesized moderator variable. METHODS Pooled relative risk (RR) estimates were calculated. Subgroup, sensitivity, and meta-regression analyses were conducted. RESULTS Totally, 33 studies (1446 cases/2697 controls) were analyzed. The vacA-s1 genotype was significantly associated with an increased risk of atrophic gastritis(AG), intestinal metaplasia(IM), and GC (RR = 1.116, 95% CI, 1.019-1.222; RR = 1.418, 95% CI, 1.035-1.942; and RR = 1.333, 95% CI, 1.115-1.593, respectively); however, the vacA m1 genotype strongly increased the risk of IM and GC, but not AG (RR = 1.571, 95% CI, 1.247-1.980 and RR = 1.431, 95% CI, 1.180-1.735, respectively). The vacA s1m1 allelic combination was linked to an increased risk of GC. The m1-type of vacA was more potent than s1 for predicting the risk of GC within the subgroups with the mean ASRs of 11/100,000-19/100,000 and less than 10/100,000. The meta-regression analysis indicated that the ASR of GC modified the association between H. pylori genotypes and GC risk, where the estimated risk was significantly decreased with increasing the mean ASRs of GC (P-values = 0.025, 0.00009, and 0.0005 for s1, m1, and s1m1, respectively). CONCLUSIONS The H. pylori vacA-s1 and vacA-m1 allelic variants strongly increased susceptibility to IM and GC; however, only s1 showed an association with AG. These associations were largely influenced by geographic variations in the GC incidence rate.
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Affiliation(s)
- Esmat Abdi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Hamid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Bahareh Safarnejad
- Department of Neurology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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Resistance Rate and Minimum Inhibitory Concentration of Metronidazole Among Helicobacter pylori Strains in Tehran, Iran. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2016. [DOI: 10.5812/archcid.34478] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Pajavand H, Alvandi A, Mohajeri P, Bakhtyari S, Bashiri H, Kalali B, Gerhard M, Najafi F, Abiri R. High Frequency of vacA s1m2 Genotypes Among Helicobacter pylori Isolates From Patients With Gastroduodenal Disorders in Kermanshah, Iran. Jundishapur J Microbiol 2015; 8:e25425. [PMID: 26862378 PMCID: PMC4740511 DOI: 10.5812/jjm.25425] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Revised: 02/05/2015] [Accepted: 04/13/2015] [Indexed: 02/06/2023] Open
Abstract
Background: Helicobacter pylori infection and related diseases outcome are mediated by a complex interplay between bacterial, host and environmental factors. Several distinct virulence factors of H. pylori have been shown to be associated with different clinical outcomes. Here we focused on vacA and cagA genotypes of H. pylori strains isolated from patients with gastric disorder. Objectives: The aim of this study was to determine the frequency of two toxins and genotypes of VacA toxin in patients referred to a central hospital in the west of Iran (Imam Reza hospital, Kermanshah) during 2011 - 2012. Patients and Methods: Samples were collected from patients infected with H. pylori. Gastric biopsy specimens from the stomach antrum and corpus were cultured. PCR analysis was performed for genotyping H. pylorivacA and cagA genes. Results: Helicobacter pylori was isolated from 48% (96/200) of patients with gastroduodenal disorders. In 81/96 (84%) cases, the cagA gene was present. Among different genotypes of vacA, two s1m2 and s2m2 genotypes were dominant with frequency of 39.5% and 50%, respectively. The frequency of the s1m1 genotype was 7.2% (7/96), which is much lower than elsewhere. H. pylori isolates with positive results for cagA gene and vacA s1m2 genotypes showed statistically significant correlation with peptic ulcer (s1m2 13/34 [38.2%] P = 0.003). However, isolates of H. pylori infection with cagA gene and vacAs2m2 genotypes were significantly associated with development of gastritis (s2m2 41/42 [97.6%] P = 0.000). Conclusions: About 90% of H. pylori strains potentially contained vacAs2m2 and s1m2 genotypes. Infection with H. pylori strain containing the cagA gene or the vacAs1m1 and s1m2 genotypes was associated with increased incidence of peptic ulcer disease (PUD).
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Affiliation(s)
- Hamid Pajavand
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Amirhooshang Alvandi
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Parviz Mohajeri
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Somaye Bakhtyari
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Homayoon Bashiri
- Department of Internal Medicine, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Behnam Kalali
- Department of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany
| | - Markus Gerhard
- Department of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany
| | - Farid Najafi
- Department of Epidemiology, Epidemiology of Cancer, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
| | - Ramin Abiri
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
- Corresponding author: Ramin Abiri, Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, P. O. Box: 6714869914, Kermanshah, IR Iran. Tel: +98-9122773648, Fax: +98-8314274623, E-mail:
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Ahmadzadeh A, Ghalehnoei H, Farzi N, Yadegar A, Alebouyeh M, Aghdaei HA, Molaei M, Zali MR, Pour Hossein Gholi MA. Association of CagPAI integrity with severeness of Helicobacter pylori infection in patients with gastritis. ACTA ACUST UNITED AC 2015; 63:252-7. [PMID: 26530303 DOI: 10.1016/j.patbio.2015.09.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 09/29/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM The Helicobacter pylori cag pathogenicity island (cagPAI) is involved in delivery of CagA effector protein and peptidoglycan into host cells and also in IL-8 induction in the human gastric tissue. Diversity of cagPAI may affect disease status and clinical outcome of the infected patients. Our study was aimed to investigate diversity of this island and its intactness in Iranian patients to investigate possible associations between cagPAI integrity and pathological changes of the infected tissue. MATERIAL/PATIENTS AND METHODS Out of the 75 patients, H. pylori strains were obtained from 30 patients with severe active gastritis (SAG) (n=11), moderate chronic gastritis (CG) (n=14) and intestinal metaplasia/dysplasia (IM) (n=5). Intactness of the cagPAI was determined using 12 sets of primer pairs specific for functionally important loci of cagPAI by polymerase chain reaction (PCR). RESULTS The cagPAI positive strains were significantly observed in patients with SAG (52.4%) in comparison to those presenting CG (33.3%) and IM (14.3%). In addition, the presence of intact cagPAI was 87.5% in H. pylori strains isolated from patients with SAG, which was higher than those obtained from patients with CG (12.5%) or IM (0%). A significant increase in the frequency of cagα-cagY and cagW-cagT segments, as exterior proteins of the CagPAI, was illustrated in strains from SAG patients compared with those from patients with CG. CONCLUSIONS Overall, these results strongly proposed an association between the severity of histopathological changes and intactness of cagPAI in the gastric tissue of patients infected with H. pylori.
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Affiliation(s)
- A Ahmadzadeh
- Molecular Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Faculty of Medicine, Ilam University of Medical Sciences, Tehran, Iran
| | - H Ghalehnoei
- Molecular Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - N Farzi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - A Yadegar
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Alebouyeh
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - H A Aghdaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Molaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M R Zali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - M A Pour Hossein Gholi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Vianna JS, Ramis IB, Halicki PCB, Gastal OL, Silva RA, Junior JS, Dos Santos DM, Chaves AL, Juliano CR, Jannke HA, da Silva LV, Von Groll A, da Silva PEA. Detection of Helicobacter pylori CagA EPIYA in gastric biopsy specimens and its relation to gastric diseases. Diagn Microbiol Infect Dis 2015; 83:89-92. [PMID: 26144892 DOI: 10.1016/j.diagmicrobio.2015.05.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Revised: 04/30/2015] [Accepted: 05/11/2015] [Indexed: 02/07/2023]
Abstract
CagA of Helicobacter pylori undergoes tyrosine phosphorylation in a region containing differing numbers of repeat sequences (EPIYAs), which can result in a modulation of the inflammatory response. This study investigated whether the presence of CagA EPIYA variations in strains of H. pylori that are positive for this region contributes to differing degrees of disease severity in the gastric mucosa. In this study, 157 H. pylori-positive patients were included, and of those, 40.8% (64/157) were infected with cagA-positive strains, which were assayed for the presence of CagA EPIYA-ABC, EPIYA-ABCC, and EPIYA-ABCCC. Peptic ulcers were significantly more prevalent in patients infected with strains containing CagA EPIYA-ABCC/ABCCC than in those with CagA EPIYA ABC strains (P=0.044). This suggests that the number of repetitions of EPIYA-C influences the development of gastroduodenal lesions, highlighting the importance and usefulness of evaluating the cagA gene sequence when making therapeutic intervention decisions in patients infected with H. pylori.
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Affiliation(s)
- Júlia Silveira Vianna
- Programa de Pós Graduação em Biotecnologia, Universidade Federal de Pelotas (UFPel), Campus Universitário, Pelotas, Rio Grande do Sul, Brazil.
| | - Ivy Bastos Ramis
- Núcleo de Pesquisas em Microbiologia Médica, Universidade Federal do Rio Grande (FURG), Rua General Osório, S/N, Rio Grande, Rio Grande do Sul, Brazil
| | | | - Otávio Leite Gastal
- Hospital Universitário São Francisco de Paula (HUSFP), Universidade Católica de Pelotas, Rua Marechal Deodoro 1123, Pelotas, Rio Grande do Sul, Brazil
| | - Renato Azevedo Silva
- Hospital Universitário São Francisco de Paula (HUSFP), Universidade Católica de Pelotas, Rua Marechal Deodoro 1123, Pelotas, Rio Grande do Sul, Brazil
| | - José Salomão Junior
- Hospital Universitário Dr. Miguel Riet Côrrea Jr, Universidade Federal do Rio Grande (FURG), Rua General Osório, S/N, Rio Grande, Rio Grande do Sul, Brazil
| | - Deise Machado Dos Santos
- Hospital Universitário Dr. Miguel Riet Côrrea Jr, Universidade Federal do Rio Grande (FURG), Rua General Osório, S/N, Rio Grande, Rio Grande do Sul, Brazil
| | - Ana Lúcia Chaves
- Hospital Universitário Dr. Miguel Riet Côrrea Jr, Universidade Federal do Rio Grande (FURG), Rua General Osório, S/N, Rio Grande, Rio Grande do Sul, Brazil
| | - Carlos Renan Juliano
- Hospital Universitário Dr. Miguel Riet Côrrea Jr, Universidade Federal do Rio Grande (FURG), Rua General Osório, S/N, Rio Grande, Rio Grande do Sul, Brazil
| | - Heitor Alberto Jannke
- Hospital Universitário São Francisco de Paula (HUSFP), Universidade Católica de Pelotas, Rua Marechal Deodoro 1123, Pelotas, Rio Grande do Sul, Brazil
| | - Lande Vieira da Silva
- Núcleo de Pesquisas em Microbiologia Médica, Universidade Federal do Rio Grande (FURG), Rua General Osório, S/N, Rio Grande, Rio Grande do Sul, Brazil
| | - Andrea Von Groll
- Núcleo de Pesquisas em Microbiologia Médica, Universidade Federal do Rio Grande (FURG), Rua General Osório, S/N, Rio Grande, Rio Grande do Sul, Brazil
| | - Pedro Eduardo Almeida da Silva
- Núcleo de Pesquisas em Microbiologia Médica, Universidade Federal do Rio Grande (FURG), Rua General Osório, S/N, Rio Grande, Rio Grande do Sul, Brazil
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Teymournejad O, Shokoohizadeh L, Mohabati Mobarez A, Amini M. Helicobacter Pylori and CagA: Relationships With Esophageal and Gastroduodenal Disorders in Iranian Patients. INTERNATIONAL JOURNAL OF ENTERIC PATHOGENS 2015. [DOI: 10.17795/ijep25022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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Vaziri F, Peerayeh SN, Alebouyeh M, Maghsoudi N, Azimzadeh P, Siadat SD, Zali MR. Novel effects of Helicobacter pylori CagA on key genes of gastric cancer signal transduction: a comparative transfection study. Pathog Dis 2015; 73:ftu021. [PMID: 25743471 DOI: 10.1093/femspd/ftu021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is now recognized as a worldwide problem. Helicobacter pylori CagA is the first bacterial oncoprotein to be identified in relation to human cancer. Helicobacter pylori CagA is noted for structural diversity in its C-terminal region (contains EPIYA motifs), with which CagA interacts with numerous host cell proteins. Deregulation of host signaling by translocated bacterial proteins provides a new aspect of microbial-host cell interaction. The aim of this study is to compare the cellular effects of two different CagA EPIYA motifs on identified signaling pathways involve in gastric carcinogenesis. To investigate the effects of CagA protein carboxyl region variations on the transcription of genes involved in gastric epithelial carcinogenesis pathways, the eukaryotic vector carrying the cagA gene (ABC and ABCCC types) was transfected into gastric cancer cell line. The 42 identified key genes of signal transduction involved in gastric cancer were analyzed at the transcription level by real-time PCR. The results of real-time PCR provide us important clue that the ABCCC oncoprotein variant can change the fate of the cell completely different from ABC type. In fact, these result proposed that the ABCCC type can induce the intestinal metaplasia, IL-8, perturbation of Crk adaptor proteins, anti-apoptotic effect and carcinogenic effect more significantly than ABC type. These data support our hypothesis of a complex interaction of host cell and these two different H. pylori effector variants that determines host cellular fate.
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Affiliation(s)
- Farzam Vaziri
- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19835-187, Tehran, Iran Department of Bacteriology, Pasteur Institute of Iran, P.O. Box: 1316943551, Tehran, Iran Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-331, Tehran, Iran
| | - Shahin N Peerayeh
- Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-331, Tehran, Iran
| | - Masoud Alebouyeh
- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19835-187, Tehran, Iran
| | - Nader Maghsoudi
- Neuroscience Research Center (NRC) and Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19615-1178, Tehran, Iran
| | - Pedram Azimzadeh
- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19835-187, Tehran, Iran
| | - Seyed D Siadat
- Department of Bacteriology, Pasteur Institute of Iran, P.O. Box: 1316943551, Tehran, Iran
| | - Mohammad R Zali
- Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19835-187, Tehran, Iran
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Su J, Zhou XY, Zhang GX. Association between Helicobacter pylori infection and migraine: A meta-analysis. World J Gastroenterol 2014; 20:14965-14972. [PMID: 25356058 PMCID: PMC4209561 DOI: 10.3748/wjg.v20.i40.14965] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 03/11/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To quantify the association between Helicobacter pylori (H. pylori) infection and migraine.
METHODS: A systematic literature search of PubMed and EMBASE was conducted from inception to December 2013. Studies that provided data dealing with H. pylori infection in patients with migraine, as well as healthy controls, were selected. Meta-analysis was carried out using the odds ratio (OR) with a fixed or random effects model, and a 95%CI for the OR was calculated. An unconditional logistic regression model was used to analyze potential parameters related to H. pylori prevalence. Subgroup analyses were conducted as methods of detection and evidence grade.
RESULTS: Five case-control studies published between 2000 and 2013 were finally identified, involving 903 patients, with a total H. pylori infection rate of 39.31%. The prevalence of H. pylori infection was significantly greater in migraineurs than in controls (44.97% vs 33.26%, OR = 1.92, 95%CI: 1.05-3.51, P = 0.001). A sensitivity test indicated that no single study dominated the combined results. Univariate regression analysis found that publication year, geographical distribution and evidence grade were relevant to the results and were the main reason for the heterogeneity. Subgroup analysis found a significantly greater infection rate of H. pylori in Asian patients with migraine, but no statistically significant infection rate in European patients. The ORs were 3.48 (95%CI: 2.09-5.81, P = 0.000) and 1.19 (95%CI: 0.86-1.65, P = 0.288), respectively.
CONCLUSION: The pooled data suggest a trend of more frequent H. pylori infections in patients with migraine.
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Shokrzadeh L, Alebouyeh M, Mirzaei T, Farzi N, Zali MR. Prevalence of multiple drug-resistant Helicobacter pylori strains among patients with different gastric disorders in Iran. Microb Drug Resist 2014; 21:105-10. [PMID: 25303151 DOI: 10.1089/mdr.2014.0081] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Emergence of multidrug-resistant (MDR) strains of Helicobacter pylori is a global health concern. This study was aimed to determine the frequency of MDR H. pylori strains in Iran. H. pylori isolates were obtained from cultured gastric biopsy samples on selective culture media after their characterization by PCR and conventional biochemical methods. The minimal inhibitory concentrations of rifampicin, ciprofloxacin, levofloxacin, ampicillin, clarithromycin, erythromycin, metronidazole, and tetracycline were determined for 111 strains that were isolated from 197 dyspeptic patients by the agar dilution method. The primary resistance rates were 61.3% (68/111) for metronidazole, 15.3% (17/111) for ampicillin, and 14.4% (16/111) for rifampicin. Resistance rates for other antimicrobials were as follows: macrolides (erythromycin or clarithromycin) 32.4% (36/111) and quinolones (levofloxacin or ciprofloxacin) 30.6% (34/111). Among the resistant strains, the rates of double and multiple drug resistance phenotypes were 22.6% (19/84) and 34.5% (29/84), respectively. The quadruple drug resistance phenotype encompasses 37.9% of the MDR strains, of which 90% of them was resistant to metronidazole. In conclusion, these results showed a high frequency of MDR phenotypes among the studied H. pylori strains in Iran. The eradication of the H. pylori strains presenting high resistance rates to macrolides, fluoroquinolones, or metronidazole could be achieved by approved tetracycline- or amoxicillin-containing regimens as alternative regimens to standard triple therapy.
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Affiliation(s)
- Leila Shokrzadeh
- 1 Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
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Yadegar A, Mobarez AM, Alebouyeh M, Mirzaei T, Kwok T, Zali MR. Clinical relevance of cagL gene and virulence genotypes with disease outcomes in a Helicobacter pylori infected population from Iran. World J Microbiol Biotechnol 2014; 30:2481-90. [PMID: 24854336 DOI: 10.1007/s11274-014-1673-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2014] [Accepted: 05/16/2014] [Indexed: 12/11/2022]
Abstract
Helicobacter pylori infection is common in Iran as in other developing countries. Certain genotypes of H. pylori have been associated with increased occurrence of chronic gastritis, peptic ulcers, and gastric adenocarcinoma. The aim of this study was to investigate the clinical relevance of cagL gene and other virulence genotypes of H. pylori isolates with clinical outcomes in Iranian patients. Totally, 126 symptomatic patients who underwent gastroduodenal endoscopy were enrolled in the study. Sixty-one H. pylori strains were isolated from the patients studied. The presence of the cagL, cagA, vacA, iceA, babA2 and sabA genes in the corresponding H. pylori isolates were determined by polymerase chain reaction and the results were compared with clinical outcomes and histopathology. The cagL, cagA, vacA s1, vacA s2, vacA m1, vacA m2, iceA1, iceA2, babA 2 , and sabA genotypes were detected in 96.7, 85.2, 75.4, 24.6, 29.5, 70.5, 42.6, 23, 96.7, and 83.6% of the isolates, respectively. The three genotypic combinations, cagL/cagA/vacAs1m1/iceA1/babA2/sabA, cagL/cagA/vacAs1m2/iceA1/babA2/sabA, and cagL/cagA/vacAs1m2/iceA2/babA2/sabA were determined as the most prevalent combined genotypes. There was a significant correlation between the presence of cagL gene and cagA positivity (P = 0.02). No significant correlation was found between the various genotypes and clinical outcomes (P > 0.05). The present study showed a very high prevalence of cagL genotype among the H. pylori isolates from Iranian patients. Our results demonstrated that neither single genotype nor combination genotypes of virulence-associated genes was significantly helpful markers for predicting the severity of gastroduodenal disease associated with H. pylori infection in Iranian patients.
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Affiliation(s)
- Abbas Yadegar
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Five-year monitoring of considerable changes in tyrosine phosphorylation motifs of the Helicobacter pylori cagA gene in Iran. J Appl Genet 2014; 55:417-22. [PMID: 24771298 DOI: 10.1007/s13353-014-0209-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 03/01/2014] [Accepted: 03/24/2014] [Indexed: 02/08/2023]
Abstract
CagA is a major virulence factor of Helicobacter pylori involved in host cell modulation. The C-terminal part of CagA containing the EPIYA motifs is highly variable and is important for the biological activity of the protein. The aim of this study was consideration of the changes in cagA tyrosine phosphorylation motifs (TPMs) of H. pylori. A set of 302 H. pylori DNA samples from the Iranian population from 2006 to 2011 was selected for the proposed study. The cagA gene and its TPMs were assessed by using polymerase chain reaction (PCR) and specific primers. The prevalence of the cagA gene in our study ranged from 91.43% to 97.06% (with an average of 95.03%). Out of the cagA-positive samples, the prevalence of TPMs A and B increased from 12.5% and 23.44% to 71.2% and 63.63%, respectively. Also, the prevalence of samples infected with Western and East Asian types of H. pylori ranged from 64.06% to 5.73% for the Western type and 17.19% to 51.59% for the East Asian type. Overall, our results showed a high prevalence of the cagA gene. Also, it seems that cagA TPMs of H. pylori is undergoing a change from the Western type to the East Asian type in Iran.
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