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Muñoz AB, Stepanian J, Solano‐Gutierrez JS, Vale FF, Trespalacios‐Rangel AA. Helicobacter pylori Infection in Colombia: Phylogeny, Resistome, and Virulome. APMIS 2025; 133:e70003. [PMID: 39930978 PMCID: PMC11811748 DOI: 10.1111/apm.70003] [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: 04/17/2024] [Revised: 11/06/2024] [Accepted: 01/27/2025] [Indexed: 02/13/2025]
Abstract
Helicobacter pylori is a successful etiologic gastric agent that reaches a prevalence around 80% in Colombia. This bacterium is extremely diverse and has shown a phylogeographic pattern. The objective of this study was to perform an analysis of genomic epidemiology of H. pylori in Colombia. We enriched our set of 29 newly sequenced Colombian H. pylori genomes with additional data from public databases, reaching a total of 221 genomes in our dataset. Phylogenetic characterization was carried out using MLST and whole genome SNP analysis. We also performed a characterized the diversity of virulence factors and mutations associated with antimicrobial resistance. Phylogenetic analyzes showed two new Colombian H. pylori clades. Furthermore, many virulence genotype combinations were found, mutations associated with resistance were found for all the studied antibiotics, highlighting 14.4% of the genomes presented profiles associated with resistance to more than one family of antibiotics. Our analyzes described the genomics of Colombian H. pylori and verify the presence of a population group formed exclusively by Colombian isolates. We demonstrated the great diversity among the isolates and that the analysis by comparative genomics of H. pylori are valuable tools to assess the diversity, virulence, and resistance of H. pylori.
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Affiliation(s)
- Angela B. Muñoz
- Infectious Diseases Research Group, Microbiology Department, Sciences FacultyPontificia Universidad JaverianaBogotáColombia
- Health Sciences FacultyUniversidad Colegio Mayor de CundinamarcaBogotáColombia
| | - Johanna Stepanian
- Infectious Diseases Research Group, Microbiology Department, Sciences FacultyPontificia Universidad JaverianaBogotáColombia
| | - Juan S. Solano‐Gutierrez
- Texas Tech University—School of Veterinary MedicineAmarilloTexasUSA
- Texas Center for Comparative Cancer Research (TC3R)AmarilloTexasUSA
| | - Filipa F. Vale
- BioISI—Instituto de Biosistemas e Ciências Integrativas, Faculdade de CiênciasUniversidade de LisboaLisboaPortugal
- Research Institute for Medicines (iMed.ULisboa), Faculty of PharmacyUniversidade de LisboaLisboaPortugal
| | - Alba A. Trespalacios‐Rangel
- Infectious Diseases Research Group, Microbiology Department, Sciences FacultyPontificia Universidad JaverianaBogotáColombia
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Elbehiry A, Marzouk E, Abalkhail A, Sindi W, Alzahrani Y, Alhifani S, Alshehri T, Anajirih NA, ALMutairi T, Alsaedi A, Alzaben F, Alqrni A, Draz A, Almuzaini AM, Aljarallah SN, Almujaidel A, Abu-Okail A. Pivotal role of Helicobacter pylori virulence genes in pathogenicity and vaccine development. Front Med (Lausanne) 2025; 11:1523991. [PMID: 39850097 PMCID: PMC11756510 DOI: 10.3389/fmed.2024.1523991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 12/13/2024] [Indexed: 01/25/2025] Open
Abstract
One of the most prevalent human infections is Helicobacter pylori (H. pylori), which affects more than half of the global population. Although H. pylori infections are widespread, only a minority of individuals develop severe gastroduodenal disorders. The global resistance of H. pylori to antibiotics has reached concerning levels, significantly impacting the effectiveness of treatment. Consequently, the development of vaccines targeting virulence factors may present a viable alternative for the treatment and prevention of H. pylori infections. This review aims to provide a comprehensive overview of the current understanding of H. pylori infection, with a particular focus on its virulence factors, pathophysiology, and vaccination strategies. This review discusses various virulence factors associated with H. pylori, such as cytotoxin-associated gene A (cagA), vacuolating cytotoxin gene (vacA), outer membrane proteins (OMPs), neutrophil-activated protein (NAP), urease (ure), and catalase. The development of vaccines based on these virulence characteristics is essential for controlling infection and ensuring long-lasting protection. Various vaccination strategies and formulations have been tested in animal models; however, their effectiveness and reproducibility in humans remain uncertain. Different types of vaccines, including vector-based vaccines, inactivated whole cells, genetically modified protein-based subunits, and multiepitope nucleic acid (DNA) vaccines, have been explored. While some vaccines have demonstrated promising results in murine models, only a limited number have been successfully tested in humans. This article provides a thorough evaluation of recent research on H. pylori virulence genes and vaccination methods, offering valuable insights for future strategies to address this global health challenge.
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Affiliation(s)
- Ayman Elbehiry
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Eman Marzouk
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Adil Abalkhail
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Wael Sindi
- Department of Population, Public and Environmental Health, General Administration of Health Services, Ministry of Defense, Riyadh, Saudi Arabia
| | - Yasir Alzahrani
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Salem Alhifani
- Department of Psychiatry, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Turki Alshehri
- Department of Dental, Alhada Armed Forces Hospital, Taif, Saudi Arabia
| | - Nuha Abdulaziz Anajirih
- Department of Medical Emergency Services, Faculty of Health Sciences, Umm Al-Qura University, Al-Qunfudah, Saudi Arabia
| | - Turki ALMutairi
- Department of Education and Training, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Ahmad Alsaedi
- Department of Education and Training, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Feras Alzaben
- Department of Food Service, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
| | - Abdullah Alqrni
- Department of Preventive Medicine, King Fahad Armed Hospital, Jeddah, Saudi Arabia
| | - Abdelmaged Draz
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Abdulaziz M. Almuzaini
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Sahar N. Aljarallah
- Department of Pharmacy Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi Arabia
| | - Abdulrahman Almujaidel
- Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Akram Abu-Okail
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
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3
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Yuan W, Shi Y, Dai S, Deng M, Zhu K, Xu Y, Chen Z, Xu Z, Zhang T, Liang S. The role of MAPK pathway in gastric cancer: unveiling molecular crosstalk and therapeutic prospects. J Transl Med 2024; 22:1142. [PMID: 39719645 PMCID: PMC11667996 DOI: 10.1186/s12967-024-05998-8] [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: 09/22/2024] [Accepted: 12/15/2024] [Indexed: 12/26/2024] Open
Abstract
Gastric cancer remains a significant health burden globally, especially prevalent in Asian and European regions. Despite a notable decline in incidence in the United States and Western Europe over recent decades, the disease's persistence underscores the urgency for advanced research in its pathogenesis and treatment strategies. Central to this pursuit is the exploration of the mitogen-activated protein kinase (MAPK) pathway, a pivotal cellular mechanism implicated in the complex processes of gastric cancer development, including cellular proliferation, invasion, migration, and metastasis. The MAPK or extracellular signal-regulated kinase pathway serves as a crucial conduit for transmitting extracellular signals to elicit intracellular responses, with its signaling cascades subject to alterations due to genetic and epigenetic variations across various diseases, prominently cancer. This review delves into the intricate role of the MAPK signaling pathway in the pathogenesis of gastric cancer, drawing upon the most recent and critical studies that shed light on MAPK pathway alterations as a gateway to the disease. It highlights the pathway's involvement in Helicobacter pylori-mediated gastric carcinogenesis and the tumorigenic processes induced by the Epstein-Barr virus, showcasing the substantial influence of miRNAs and lncRNAs in modulating gastric cancer's biological properties through their interaction with the MAPK pathway. Furthermore, the review extends into the therapeutic arena, discussing the promising impacts of herbal medicines, MAPK pathway inhibitors, and immunosuppressants on mitigating gastric cancer's progression. Through an exhaustive examination of the MAPK pathway's multifaceted role in gastric cancer, from molecular crosstalks to therapeutic prospects, this review aspires to contribute to the ongoing efforts in understanding and combating this global health challenge, paving the way for novel therapeutic interventions and improved patient outcomes.
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Affiliation(s)
- Weiwei Yuan
- Department of Thyroid Surgery, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China
| | - Yin Shi
- Department of Internal Medicine, Yiwu Maternity and Children Hospital, Yiwu, Zhejiang, China
| | - Shiping Dai
- Department of General Surgery, Wuwei City People's Hospital, No.256, West Street, Wuwei, 238300, China
| | - Mao Deng
- Department of General Surgery, Wuwei City People's Hospital, No.256, West Street, Wuwei, 238300, China
| | - Kai Zhu
- Department of General Surgery, Wuwei City People's Hospital, No.256, West Street, Wuwei, 238300, China
| | - Yuanmin Xu
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Zhangming Chen
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Zhou Xu
- Department of Thyroid Surgery, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China.
| | - Tianlong Zhang
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
| | - Song Liang
- Department of General Surgery, The Lu'an Affiliated Hospital of Anhui Medical University, Lu'an People's Hospital, Lu'an, 237000, China.
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Elghannam MT, Hassanien MH, Ameen YA, Turky EA, ELattar GM, ELRay AA, ELTalkawy MD. Helicobacter pylori and oral-gut microbiome: clinical implications. Infection 2024; 52:289-300. [PMID: 37917397 PMCID: PMC10954935 DOI: 10.1007/s15010-023-02115-7] [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: 07/06/2023] [Accepted: 10/09/2023] [Indexed: 11/04/2023]
Abstract
More than half of the world's population are colonized with H. pylori; however, the prevalence varies geographically with the highest incidence in Africa. H. pylori is probably a commensal organism that has been associated with the development of gastritis, ulcers, and gastric cancer. H. pylori alone is most probably not enough for the development of gastric carcinoma, but evidence for its association with the disease is high and has, therefore, been classified by the International Agency for Research on Cancer as a Class 1 carcinogen. Bacteroidetes and Fusobacteria positively coexisted during H. pylori infection along the oral-gut axis. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Therefore, therapy regimens integrated with probiotics may abolish the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient's compliance. The eradication therapy not only affects gut microbiome but also affects the oral microbiome with robust predominance of harmful bacteria. However, there have been reports of a protective role of H. pylori in Barrett's esophagus, esophageal adenocarcinoma, eosinophilic esophagitis, IBD, asthma, and even multiple sclerosis. Therefore, eradication therapy should be carefully considered, and test to treat policy should be tailored to specific communities especially in highly endemic areas. Supplementation of probiotics, prebiotics, herbals, and microbial metabolites to reduce the negative effects of eradication therapy should be considered. After failure of many eradication attempts, the benefits of H. pylori eradication should be carefully balanced against the risk of adverse effects especially in the elderly, persons with frailty, and intolerance to antibiotics.
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Affiliation(s)
- Maged T Elghannam
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt.
| | - Moataz H Hassanien
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Yosry A Ameen
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Emad A Turky
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Gamal M ELattar
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Ahmed A ELRay
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Mohammed D ELTalkawy
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
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5
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Zhang L, Zhang D, Wei L, Zhou Y, Li X, Chen R, Zhang X, Chen S, Bai F. H. pylori infection and osteoporosis: a large-scale observational and mendelian randomization study. BMC Infect Dis 2024; 24:305. [PMID: 38475712 DOI: 10.1186/s12879-024-09196-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 03/06/2024] [Indexed: 03/14/2024] Open
Abstract
PURPOSE There is controversy concerning the relationship between Helicobacter pylori (H. pylori) infection and osteoporosis. This study is to examine the causal relationship between H. pylori infection and osteoporosis and to analyze the potential mechanism underlying the relationship. METHODS The clinical data of H. pylori infection and bone mineral density from patients or physical examiner with good general condition in our hospital between September 2019 and September 2020 were retrospectively collected. The relationship between H. pylori infection and osteoporosis was compared and analyzed, using logistic regression to examine the potential mechanism underlying the association. To investigate the causal effects of H. pylori infection and osteoporosis, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis. RESULTS A total of 470 patients were positive for H. pylori, with a detection rate of 52.22%. It was found that age, SBP, FPG, DBP, ALB, LDL-C, hs-CRP, and OC were positively correlated with osteoporosis, while negative correlations were observed with BMI, LYM, ALB, TP, TG, HDL-C, SCr, UA, and VitD. After stratified analysis of sex and age, it was found that there was a significant correlation between H. pylori infection and osteoporosis. The levels of SBP, ALP, FPG, LDL-C, hs-CRP, and OC in both H. pylori-positive group and osteoporosis group were higher than those in the H. pylori-negative group while the levels of BMI, ALB, TP, HDL-C, SCr, UA, and VitD in the positive group were significantly lower than those in the negative group. Logistic regression analyses with gender and age showed that ALB, FPG, HDL-C, and VitD were common risk factors for osteoporosis and H. pylori infection. In the MR analysis, the IVW results found a positive effect of H. pylori infection on osteoporosis (OR = 1.0017, 95% CI: 1.0002-1.0033, P = 0.0217). Regarding the reverse direction analysis, there was insufficient evidence to prove the causal effects of osteoporosis on H. pylori infection. CONCLUSION Our study provides evidence for causal effects of H. pylori infection on osteoporosis. H. pylori may affect osteoporosis through serum albumin, high-density lipoprotein, fasting blood glucose and vitamin D.
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Affiliation(s)
- Ling Zhang
- Department of Hospital infection management, LinYi people's Hospital, LinYi, Shandong Province, China
| | - Daya Zhang
- Graduate School of Hainan Medical University, Haikou, China
| | - Ling Wei
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, #368, Longhua District, Haikou, Hainan Province, China
- The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, China
| | - Yan Zhou
- The Third School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
| | - Ximei Li
- The Third School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
| | - Runxiang Chen
- Graduate School of Hainan Medical University, Haikou, China
| | - Xiaodong Zhang
- Graduate School of Hainan Medical University, Haikou, China
| | - Shiju Chen
- Graduate School of Hainan Medical University, Haikou, China
| | - Feihu Bai
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Yehai Avenue, #368, Longhua District, Haikou, Hainan Province, China.
- The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, China.
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6
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Ali A, AlHussaini KI. Helicobacter pylori: A Contemporary Perspective on Pathogenesis, Diagnosis and Treatment Strategies. Microorganisms 2024; 12:222. [PMID: 38276207 PMCID: PMC10818838 DOI: 10.3390/microorganisms12010222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/07/2024] [Accepted: 01/15/2024] [Indexed: 01/27/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and is associated with various gastrointestinal disorders. H. pylori is a pervasive pathogen, infecting nearly 50% of the world's population, and presents a substantial concern due to its link with gastric cancer, ranking as the third most common cause of global cancer-related mortality. This review article provides an updated and comprehensive overview of the current understanding of H. pylori infection, focusing on its pathogenesis, diagnosis, and treatment strategies. The intricate mechanisms underlying its pathogenesis, including the virulence factors and host interactions, are discussed in detail. The diagnostic methods, ranging from the traditional techniques to the advanced molecular approaches, are explored, highlighting their strengths and limitations. The evolving landscape of treatment strategies, including antibiotic regimens and emerging therapeutic approaches, is thoroughly examined. Through a critical synthesis of the recent research findings, this article offers valuable insights into the contemporary knowledge of Helicobacter pylori infection, guiding both clinicians and researchers toward effective management and future directions in combating this global health challenge.
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Affiliation(s)
- Asghar Ali
- Clinical Biochemistry Laboratory, Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India
| | - Khalid I. AlHussaini
- Department of Internal Medicine, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 4233-13317, Saudi Arabia
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7
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Graham DY. Helicobacter pylori. Curr Top Microbiol Immunol 2024; 445:127-154. [PMID: 34224014 DOI: 10.1007/82_2021_235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Helicobacter pylori (H. pylori) is an important human pathogen etiologically associated with peptic ulcers and gastric cancer. The infection is present in approximately one-half of the world's population. Population-based H. pylori eradiation has confirmed that cure or prevention of the infection produces a marked reduction in gastric cancer and peptic ulcer disease. Antimicrobial therapy has become increasingly ineffective, and complexity and costs of antimicrobial therapy for infected individuals residing in and, immigrating from, the developing world combined with the cost of treatment for cancer make vaccine development a cost-effective alternative. Challenge studies allowed making a "go-no go" decision regarding vaccine effectiveness. We provide detailed protocols regarding challenge strain selection and administration as well as guidance regarding the clinical and laboratory tests used to confirm and monitor experimental infection. Experience shows that reliance of noninvasive methods led to the erroneous conclusion that some subjects were not infected. The current data suggests that histologic assessment of gastric mucosal biopsies may be one of the most sensitive and specific means of assessment of the presence of experimental infection as well as of successful H. pylori eradication. We recommend detailed recommendations for acquiring, processing, embedding, sectioning, and examining the gastric biopsies.
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Affiliation(s)
- David Y Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, RM 3A-390A (111D), 2002 Holcombe Boulevard, Houston, TX, 77030, USA.
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8
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Al-Hazmi NE, Naguib DM. Control the carcinogenic bacteria with new polysaccharides from agricultural wastes. Microb Pathog 2023; 184:106343. [PMID: 37709103 DOI: 10.1016/j.micpath.2023.106343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 09/07/2023] [Accepted: 09/10/2023] [Indexed: 09/16/2023]
Abstract
Agriculture activities industries produce a huge amount of waste every year. Agricultural wastes are a great source of natural polysaccharides characterized by accessibility, biocompatibility, and ease of modification. Finding new safe antibacterial agents has become one of the top priorities of health organizations worldwide. This priority emerged from the antibiotic resistance pathogenic bacteria hazard. Carcinogenic bacteria are one of the most dangerous antibiotic-resistant pathogenic bacteria. This study tries to investigate the antibacterial activity of polysaccharides from some agricultural wastes against carcinogenic bacteria related to gastrointestinal cancers. We determined the antibacterial activity (in terms of minimum inhibitory concentration (MIC)) and the biofilm reduction capacity. We studied the mechanism of the antibacterial activity by determining the effect of the MIC of the extracted polysaccharides on the plasma membrane permeability and the bacterial DNA content. All extracted polysaccharides showed effective antibacterial activity with low MICs ranging from 2 to 20 μg/mL. The barely straw polysaccharides showed the highest MIC (19.844 μg/mL) against Bacteroides fragilis, while the grape bagasse showed the lowest MIC (2.489 μg/mL) against Helicobacter pylori. The extracted polysaccharide showed high antibiofilm activity. Their capacity to reduce the formation of the pathogenic biofilm ranged from 75 to 95%. Regarding the antibacterial mechanism, the extracted polysaccharides showed destructive action on the DNA and the plasma membrane permeability. The bacterial DNA change percent after the treatment with the different polysaccharides ranged from 29% to -58%. The plasma membrane permeability increased by a high percentage, ranging from 92% to 123%. Agricultural waste polysaccharides are a promising antibacterial agent against antibiotic-resistant carcinogenic bacteria.
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Affiliation(s)
- Nawal E Al-Hazmi
- Department of Chemistry, Division of Biology (Microbiology), University College of Qunfudah, Umm Al-Qura University, Qunfudah, Saudi Arabia
| | - Deyala M Naguib
- Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt; Biology Department, Faculty of Science and Arts in Al-Mikhwah, Al-Baha University, Al-Mikhwah, Saudi Arabia.
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9
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González Segovia R, Romo Lozano Y, Rodríguez MG, Montañez Flores AL, González Macías J. Identification of serologically active Helicobacter pylori antigens related to alterations in serum pepsinogen levels. Rev Argent Microbiol 2023; 55:355-365. [PMID: 37385833 DOI: 10.1016/j.ram.2023.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 12/20/2022] [Accepted: 04/14/2023] [Indexed: 07/01/2023] Open
Abstract
Gastric adenocarcinoma is associated with Helicobacter pylori infection. The transition to a carcinogenic process is preceded by glandular atrophy and serum levels of pepsinogen I and II (PGI and PGII) correlate with this type of gastric lesions. Possible associations of serum PG levels in relation to the frequency of serological activity against H. pylori antigens were studied. Serum samples from patients with gastric pathology associated with H. pylori (n=26) and asymptomatic individuals as controls (n=37) were used. Seroactive antigens were identified by immunoblot using a protein extract of H. pylori. The antibody titers anti-H. pylori and the concentration of PGs in serum was determined by ELISA. Thirty-one seroactive antigens were identified, nine of which exhibited a differential frequency between both groups (116.7, 68.8, 61.9, 54.9, 45.6, 38.3, 36.5, 33.8 and 30.1kDa) and only 3 were related to altered levels of PGs in serum. In the control group, the seropositivity of the 33.8kDa antigen was related to an increase in PGII, while the 68.8kDa antigen was related to normal PG values (decreased PGII and elevated PGI/PGII levels) indicating that seropositivity to this antigen could be a protective factor to gastric pathology. The seropositivity of the 54.9kDa antigen was related to altered values of PGs indicative of inflammation and gastric atrophy (increased in PGII and decreased in PGI/PGII). The identification of serum alterations in pepsinogen levels related to seropositivity to H. pylori 33.8, 54.9 and 68.8kDa antigens sets a precedent for further study as possible prognostic serological biomarkers.
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Affiliation(s)
- Rodolfo González Segovia
- Departamento de Microbiología, Universidad Autónoma de Aguascalientes, Av. Universidad 940, CP 20100, Aguascalientes, Mexico.
| | - Yolanda Romo Lozano
- Departamento de Microbiología, Universidad Autónoma de Aguascalientes, Av. Universidad 940, CP 20100, Aguascalientes, Mexico
| | - Martín Gerardo Rodríguez
- Departamento de Fisiología y Farmacología, Universidad Autónoma de Aguascalientes, Av. Universidad 940, CP 20100, Aguascalientes, Mexico
| | | | - Juan González Macías
- Servicio de Gastroenterología, Unidad Médica de Atención Ambulatoria del IMSS, Av. de la Convención de 1914 Nte. No. 102, Col. Industrial, CP 20030, Aguascalientes, Mexico
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Manfredi M, Gismondi P, Iuliano S. Is Helicobacter pylori Anyway Pathogen in Children? INQUIRY : A JOURNAL OF MEDICAL CARE ORGANIZATION, PROVISION AND FINANCING 2023; 60:469580231154650. [PMID: 36803205 PMCID: PMC9940224 DOI: 10.1177/00469580231154650] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/20/2023]
Abstract
Helicobacter pylori (H. pylori) infection is a continuous challenge for both gastroenterologists and pediatricians. The international guidelines regarding diagnostic and treatment pathways differ between adults and children. The pediatric guidelines are more restrictive because children are rarely affected by serious consequences, particularly in Western countries. Therefore, infected children should be treated only after a careful case-by-case evaluation by a pediatric gastroenterologist. In any case, recent studies are confirming an increasingly all-around pathological role of H. pylori even in asymptomatic children. For these reasons, following the current evidence, we feel that H. pylori-infected children could be treated starting in pre-adolescence, particularly in Eastern countries, because their stomachs have already begun to develop the biomarkers of gastric damage. Therefore, we believe that H. pylori is anyway pathogen in children. Nevertheless, the possible beneficial role of H. pylori in humans has not yet been conclusively disproved.
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Affiliation(s)
- Marco Manfredi
- Azienda USL-IRCCS di Reggio Emilia, Maternal and Child Department, Pediatric Unit, Sant’Anna Hospital, Castelnovo ne Monti, Reggio Emilia, Italy,Marco Manfredi, Azienda USL-IRCCS di Reggio Emilia, Maternal and Child Department, Pediatric Unit, Sant’Anna Hospital, via Roma, 2 - Castelnovo ne Monti, Reggio Emilia 42122, Italy.
| | - Pierpacifico Gismondi
- Week Hospital, Pietro Barilla Children’s Hospital, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Silvia Iuliano
- Pediatric Gastroenterology, Pietro Barilla Children’s Hospital, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
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11
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Freire de Melo F, Marques HS, Rocha Pinheiro SL, Lemos FFB, Silva Luz M, Nayara Teixeira K, Souza CL, Oliveira MV. Influence of Helicobacter pylori oncoprotein CagA in gastric cancer: A critical-reflective analysis. World J Clin Oncol 2022; 13:866-879. [PMID: 36483973 PMCID: PMC9724182 DOI: 10.5306/wjco.v13.i11.866] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 09/20/2022] [Accepted: 10/11/2022] [Indexed: 11/21/2022] Open
Abstract
Gastric cancer is the fifth most common malignancy and third leading cancer-related cause of death worldwide. Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3% of the world's population and represents the main risk factor for the onset of gastric neoplasms. CagA is the most important virulence factor in H. pylori, and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions. Upon translocation and tyrosine phosphorylation, CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways, thereby disrupting cell proliferation, differentiation and apoptosis. All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes. In this sense, once gastric cancer sets in, its perpetuation is independent of the presence of the oncoprotein, characterizing a "hit-and-run" carcinogenic mechanism. Therefore, this review aims to describe H. pylori- and CagA-related oncogenic mechanisms, to update readers and discuss the novelties and perspectives in this field.
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Affiliation(s)
- Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
| | - Hanna Santos Marques
- Campus Vitória da Conquista, Universidade Estadual do Sudoeste da Bahia, Vitória da Conquista 45029-094, Brazil
| | - Samuel Luca Rocha Pinheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
| | - Fabian Fellipe Bueno Lemos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
| | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
| | | | - Cláudio Lima Souza
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
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12
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Ferreira R, Sousa C, Gonçalves RFS, Pinheiro AC, Oleastro M, Wagemans J, Lavigne R, Figueiredo C, Azeredo J, Melo LDR. Characterization and Genomic Analysis of a New Phage Infecting Helicobacter pylori. Int J Mol Sci 2022; 23:ijms23147885. [PMID: 35887231 PMCID: PMC9319048 DOI: 10.3390/ijms23147885] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/11/2022] [Accepted: 07/13/2022] [Indexed: 02/04/2023] Open
Abstract
Helicobacter pylori, a significant human gastric pathogen, has been demonstrating increased antibiotic resistance, causing difficulties in infection treatment. It is therefore important to develop alternatives or complementary approaches to antibiotics to tackle H. pylori infections, and (bacterio)phages have proven to be effective antibacterial agents. In this work, prophage isolation was attempted using H. pylori strains and UV radiation. One phage was isolated and further characterized to assess potential phage-inspired therapeutic alternatives to H. pylori infections. HPy1R is a new podovirus prophage with a genome length of 31,162 bp, 37.1% GC, encoding 36 predicted proteins, of which 17 were identified as structural. Phage particles remained stable at 37 °C, from pH 3 to 11, for 24 h in standard assays. Moreover, when submitted to an in vitro gastric digestion model, only a small decrease was observed in the gastric phase, suggesting that it is adapted to the gastric tract environment. Together with its other characteristics, its capability to suppress H. pylori population levels for up to 24 h post-infection at multiplicities of infection of 0.01, 0.1, and 1 suggests that this newly isolated phage is a potential candidate for phage therapy in the absence of strictly lytic phages.
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Affiliation(s)
- Rute Ferreira
- CEB—Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal; (R.F.); (C.S.); (R.F.S.G.); (A.C.P.); (J.A.)
- LABBELS—Associate Laboratory, Braga/Guimarães, Portugal
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal;
| | - Cláudia Sousa
- CEB—Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal; (R.F.); (C.S.); (R.F.S.G.); (A.C.P.); (J.A.)
- LABBELS—Associate Laboratory, Braga/Guimarães, Portugal
| | - Raquel F. S. Gonçalves
- CEB—Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal; (R.F.); (C.S.); (R.F.S.G.); (A.C.P.); (J.A.)
- LABBELS—Associate Laboratory, Braga/Guimarães, Portugal
| | - Ana Cristina Pinheiro
- CEB—Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal; (R.F.); (C.S.); (R.F.S.G.); (A.C.P.); (J.A.)
- LABBELS—Associate Laboratory, Braga/Guimarães, Portugal
| | - Mónica Oleastro
- Department of Infectious Diseases, National Institute of Health Doctor Ricardo Jorge (INSA), 1649-016 Lisbon, Portugal;
| | - Jeroen Wagemans
- Laboratory of Gene Technology, KU Leuven, 3001 Leuven, Belgium; (J.W.); (R.L.)
| | - Rob Lavigne
- Laboratory of Gene Technology, KU Leuven, 3001 Leuven, Belgium; (J.W.); (R.L.)
| | - Ceu Figueiredo
- i3S—Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal;
- Ipatimup—Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal
- Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Joana Azeredo
- CEB—Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal; (R.F.); (C.S.); (R.F.S.G.); (A.C.P.); (J.A.)
- LABBELS—Associate Laboratory, Braga/Guimarães, Portugal
| | - Luís D. R. Melo
- CEB—Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal; (R.F.); (C.S.); (R.F.S.G.); (A.C.P.); (J.A.)
- LABBELS—Associate Laboratory, Braga/Guimarães, Portugal
- Correspondence:
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13
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El Hafa F, Wang T, Ndifor VM, Jin G. Association between Helicobacter pylori antibodies determined by multiplex serology and gastric cancer risk: A meta-analysis. Helicobacter 2022; 27:e12881. [PMID: 35212073 DOI: 10.1111/hel.12881] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 01/17/2022] [Accepted: 01/30/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Previous studies have reported the association between limited number of Helicobacter pylori (H. pylori) antigens and gastric cancer (GC) risk. The present study evaluated the association between serum antibodies against 15 different H. pylori proteins measured by using multiplex serology assay and GC risk. METHODS We searched PubMed databases, Embase, Web of Science, and Cochrane Library for relevant articles. A meta-analysis was used to pool studies and to estimate odds ratios (ORs) with 95% confidence intervals (95%CIs) of different H. pylori antigens associated with GC risk. Heterogeneity was investigated using Cochran's Q test and I-squared statistic. RESULTS Nine studies were identified, with a total of 3209 GC cases and 6964 controls. Five H. pylori virulence factors were significantly associated with non-cardia GC risk at p-value <0.0033 including: CagA (OR = 3.22, 95%CI: 2.10-4.94), HP0305 (OR = 1.72, 95%CI: 1.32-2.25), HyuA (OR = 1.42, 95%CI: 1.13-1.79), Omp (OR = 1.83, 95%CI: 1.30-2.58), and VacA (OR = 2.05, 95%CI: 1.67-2.52). However, none of the 15 antigens was associated with cardia GC risk. In subgroup analysis by ethnicity, we identified 7 antigens associated with the risk of non-cardia GC among East Asian while only two antigens were identified in European population. Nevertheless, CagA and GroEL showed a stronger association in Caucasian (CagA OR = 5.83, 95%CI: 3.31-10.26; GroEL OR = 3.66, 95%CI: 1.58-8.50) compared with East Asian (CagA OR = 2.20, 95% CI: 1.85-2.61; GroEL OR = 1.47, 95%CI: 1.29-1.68). CONCLUSIONS This study determined that H. pylori infection increases the risk of non-cardia GC with differential effects by its virulence factors and with different patterns among East Asian and European populations. These results advance the understanding of the effect of H. pylori on GC.
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Affiliation(s)
- Fadoua El Hafa
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Tianpei Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Nanjing Medical University, Nanjing, China.,Public Health Institute of Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Valerie Mbuhnwi Ndifor
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Guangfu Jin
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Nanjing Medical University, Nanjing, China.,Public Health Institute of Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
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14
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The role of non-Helicobacter pylori bacteria in the pathogenesis of gastroduodenal diseases. Gut Pathog 2022; 14:19. [PMID: 35606878 PMCID: PMC9125830 DOI: 10.1186/s13099-022-00494-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 05/04/2022] [Indexed: 02/06/2023] Open
Abstract
Over the past decade, the development of next-generation sequencing for human microbiota has led to remarkable discoveries. The characterization of gastric microbiota has enabled the examination of genera associated with several diseases, including gastritis, precancerous lesions, and gastric cancer. Helicobacter pylori (H. pylori) is well known to cause gastric dysbiosis by reducing diversity, because this bacterium is the predominant bacterium. However, as the diseases developed into more severe stages, such as atrophic gastritis, premalignant lesion, and gastric adenocarcinoma, the dominance of H. pylori began to be displaced by other bacteria, including Streptococcus, Prevotella, Achromobacter, Citrobacter, Clostridium, Rhodococcus, Lactobacillus, and Phyllobacterium. Moreover, a massive reduction in H. pylori in cancer sites was observed as compared with noncancer tissue in the same individual. In addition, several cases of H. pylori-negative gastritis were found. Among these individuals, there was an enrichment of Paludibacter, Dialister, Streptococcus, Haemophilus parainfluenzae, and Treponema. These remarkable findings suggest the major role of gastric microbiota in the development of gastroduodenal diseases and led us to the hypothesis that H. pylori might not be the only gastric pathogen. The gastric microbiota point of view of disease development should lead to a more comprehensive consideration of this relationship.
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Kiselev HY, Gorlenko CL, El-Taravi YA, Porubayeva EE, Budanova EV. Modern knowledge on pathogenesis, diagnosis and treatment of helicobacter infection. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:15-26. [DOI: 10.31146/1682-8658-ecg-193-9-15-26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Since its discovery, H. pylori infection is known as one of the risk factor for the development of gastritis, peptic ulcer, GIT tumors and numerous other diseases such as psoriasis. Infection caused by H. pylori is posed as the top oncogene in the risk of the development of gastrocarcinoma (First class oncogene by Classification of International Agency for Research of Cancer). That is why the elaboration of fast and accurate methods of diagnosis (non-invasive methods especially) and proper treatment of Helicobacter infection is still very important. Throughout the time, knowledge about pathogenesis of Helicobacter infection have been expanded with the detection of adhesins, chemotaxins and multiple virulence factors related to invasion, adhesion and cytotoxicity of H. pylori. Invasive and non-invasive methods of diagnostics are currently being improved in effectiveness and accuracy. But still, due to different factors (e. g., dramatically increasing drug resistance), eradication of H. pylori remains big problem world-wide. Our review represents modern data on pathogenesis, diagnostics and treatment of Helicobacter infection.
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16
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Abstract
El cuerpo humano está expuesto continuamente a microorganismos tanto fijos como transitorios, así como sus metabolitos tóxicos, lo cual puede conducir a la aparición y progresión del cáncer en sitios distantes al hábitat particular de cada microbio. Diversos estudios científicos han hecho posible entender la relación estrecha que existe entre microbioma y cáncer, ya que los componentes del primero, al tener la capacidad de migrar a diferentes zonas del cuerpo, pueden contribuir al desarrollo de diversas enfermedades crónicas. Los estudios de metagenómica sugieren que la disbiosis, en la microbiota comensal, está asociada con trastornos inflamatorios y varios tipos de cáncer, los cuales pueden ocurrir por sus efectos sobre el metabolismo, la proliferación celular y la inmunidad. La microbiota puede producir el cáncer cuando existen condiciones predisponentes, como en la etapa inicial de la progresión tumoral (iniciación), inestabilidad genética, susceptibilidad a la respuesta inmune del huésped, a la progresión y la respuesta a la terapia. La relación más estrecha, entre el microbioma y el cáncer, es a través de la desregulación del sistema inmune. En este trabajo revisamos las actuales evidencias sobre la asociación entre la microbiota y algunos tipos de cáncer como el cáncer gástrico, colorrectal, próstata, ovario, oral, pulmón y mama.
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Affiliation(s)
- Francisco Arvelo
- Centro de Biociencias, Fundación Instituto de Estudios Avanzados-IDEA, Caracas, Venezuela
| | - Felipe Sojo
- Centro de Biociencias, Fundación Instituto de Estudios Avanzados-IDEA, Caracas, Venezuela
| | - Carlos Cotte
- Laboratorio de Cultivo de Tejidos y Biología de Tumores, Instituto de Biología Experimental, Universidad Central de Venezuela, Caracas, Venezuela
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17
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Wojtyś MI, Jaźwiec R, Kazazić S, Leščić Ašler I, Knežević P, Aleksić Sabo V, Luić M, Jagusztyn-Krynicka EK, Bzowska A. A comprehensive method for determining cellular uptake of purine nucleoside phosphorylase and adenylosuccinate synthetase inhibitors by H. pylori. Appl Microbiol Biotechnol 2021; 105:7949-7967. [PMID: 34562116 PMCID: PMC8502122 DOI: 10.1007/s00253-021-11510-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 08/02/2021] [Accepted: 08/06/2021] [Indexed: 12/02/2022]
Abstract
Due to the growing number of Helicobacter pylori strains resistant to currently available antibiotics, there is an urgent need to design new drugs utilizing different molecular mechanisms than those that have been used up to now. Enzymes of the purine salvage pathway are possible targets of such new antibiotics because H. pylori is not able to synthetize purine nucleotides de novo. The bacterium's recovery of purines and purine nucleotides from the environment is the only source of these essential DNA and RNA building blocks. We have identified formycins and hadacidin as potent inhibitors of purine nucleoside phosphorylase (PNP) and adenylosuccinate synthetase (AdSS) from H. pylori - two key enzymes of the purine salvage pathway. However, we have found that these compounds are not effective in H. pylori cell cultures. To address this issue, we have developed a universal comprehensive method for assessing H. pylori cell penetration by drug candidates, with three alternative detection assays. These include liquid chromatography tandem mass spectrometry, UV absorption, and inhibition of the target enzyme by the tested compound. Using this approach, we have shown that cellular uptake by H. pylori of formycins and hadacidin is very poor, which reveals why their in vitro inhibition of PNP and AdSS and their effect on H. pylori cell cultures are so different. The cell penetration assessment method developed here will be extremely useful for validating the cellular uptake of other drug candidates, facilitating the design of new potent therapeutic agents against H. pylori. KEY POINTS: • A method for assessing H. pylori cells penetration by drug candidates is described. • Three alternative detection assays that complement each other can be used. • The method may be adapted for other bacteria as well.
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Affiliation(s)
- Marta Ilona Wojtyś
- Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Pasteura 5, 02-093, Warsaw, Poland
- Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096, Warsaw, Poland
| | - Radosław Jaźwiec
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106, Warsaw, Poland
| | - Saša Kazazić
- Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, POB 180, 10002, Zagreb, Croatia
| | - Ivana Leščić Ašler
- Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, POB 180, 10002, Zagreb, Croatia
| | - Petar Knežević
- Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 2, IV-14, 21000, Novi Sad, Republic of Serbia
| | - Verica Aleksić Sabo
- Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 2, IV-14, 21000, Novi Sad, Republic of Serbia
| | - Marija Luić
- Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, POB 180, 10002, Zagreb, Croatia
| | | | - Agnieszka Bzowska
- Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Pasteura 5, 02-093, Warsaw, Poland.
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18
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Ouyang Y, Zhu Z, Huang L, Zeng C, Zhang L, Wu WK, Lu N, Xie C. Research Trends on Clinical Helicobacter pylori Eradication: A Bibliometric Analysis from 1983 to 2020. Helicobacter 2021; 26:e12835. [PMID: 34258827 DOI: 10.1111/hel.12835] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/13/2021] [Accepted: 07/01/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Numerous studies related to Helicobacter pylori (H. pylori) eradication have been published since the discovery of H. pylori. This study aimed to use a quantitative method to assess the development of this field. MATERIALS AND METHODS We performed a search of related articles from Web of Science published in 1983-2020 using a combination of the search terms "H. pylori" and "eradication". Eligible studies were included after a two-stage screening process, and the following data were extracted: title, author, institution, country, study type, sample size, eradication regimen, publication year, number of citations, journal, and H-index. RESULTS A total of 1402 studies were finally identified. The results showed that the period from 1994-2003 was the most influential period in this field. Italy and the USA were dominant countries in this field, while China's publication number increased sharply in the last ten years. Baylor College of Medicine was the most influential institution. Alimentary Pharmacology Therapeutics was the most productive journal. The effects of H. pylori eradication on peptic ulcers and gastric cancer and H. pylori eradication therapy were the most cited topics in this field. After the publish of Maastricht/Florence Ⅳ guideline, the research of quadruple therapy was more than triple therapy. Bismuth-containing quadruple therapy became the most focused regimen after Maastricht/Florence Ⅴ guideline. CONCLUSIONS In this study, we summarized the characteristics of the publications; identified the most influential countries, institutions, journals; identified the popular research topics and eradication regimen of clinical H. pylori eradication.
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Affiliation(s)
- Yaobin Ouyang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China
| | - Zhihao Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China
| | - Li Huang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China
| | - Chuanfei Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China
| | - Lin Zhang
- Department of Anaesthesia and Intensive Care, State Key Laboratory of Digestive Diseases, Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - William Kk Wu
- Department of Anaesthesia and Intensive Care, State Key Laboratory of Digestive Diseases, Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Nonghua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China
| | - Chuan Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Province, China
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19
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Miao P, Guan L. Association of Dietary Cholesterol Intake With Risk of Gastric Cancer: A Systematic Review and Meta-Analysis of Observational Studies. Front Nutr 2021; 8:722450. [PMID: 34458311 PMCID: PMC8387575 DOI: 10.3389/fnut.2021.722450] [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: 06/08/2021] [Accepted: 07/06/2021] [Indexed: 01/12/2023] Open
Abstract
Background: Many case–control studies have investigated the association between dietary cholesterol and gastric cancer, yielding inconsistent findings. We carried out a systematic review and meta-analysis of observational studies to assess the relationship between dietary cholesterol intake and gastric cancer among adults. Methods: PubMed, Scopus, and Google Scholar were systematically searched to identify articles that evaluated the association of dietary cholesterol with gastric cancer up to May 2021. Pooled odds ratio (ORs) and 95% confidence intervals (CIs) were computed using random-effects models. Dose–response analysis was used to explore the shape and strength of the association. Results: Fourteen case–control studies with 6,490 gastric cancer patients and 17,793 controls met our inclusion criteria. In the meta-analysis of the highest vs. the lowest dietary cholesterol categories, a significantly higher (~35%) risk of gastric cancer was observed in association with high cholesterol consumption (pooled OR: 1.35, 95% CI: 1.29–1.62, I2 = 68%; 95%CI: 45–81%). Subgroup analysis also showed this positive relationship in population-based case–control studies, those conducted on non-US countries, those with a higher number of cases and high-quality studies, those that collected dietary data via interviews, studies not adjusted for Helicobacter pylori infection, and studies where the body mass index was controlled. Besides, a non-linear dose–response association was also identified (P = 0.03). Conclusion: This study demonstrated that dietary cholesterol intake could significantly augment the risk of gastric cancer in case–control studies. Prospective cohort studies with large sample sizes and long durations of follow-up are required to verify our results.
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Affiliation(s)
- Peng Miao
- General Surgery Department, The First Hospital of China Medical University, Shenyang, China
| | - Lin Guan
- Gastroenterology Department, The First Hospital of China Medical University, Shenyang, China
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20
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Prakosa AW, Miftahussurur M, Juniastuti J, Waskito LA, Doohan D, Fauzia KA, Rezkitha YAA, Sugihartono T, Syam AF, Uchida T, Yamaoka Y. Characterization of Helicobacter pylori tlyA and Its Association with Bacterial Density. Dig Dis 2021; 40:417-426. [PMID: 34515099 DOI: 10.1159/000518538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 07/19/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND In the recent studies, a less virulent Helicobacter pylori variant could still colonize the human stomach and induce gastric inflammation, suggesting the involvement of other virulence factors, such as TlyA hemolysin. Nevertheless, the association of TlyA in the pathogenesis of H. pylori infection remains unclear. We investigated the tlyA profile and determined its relationship with gastritis severity. METHODS An observational study was conducted using DNA stocks and secondary data from previous studies. The tlyA variant was examined by NGS and confirmed with polymerase chain reaction. Gastritis severity was categorized by the Updated Sydney System. The relationship between a variant of tlyA and gastritis severity was determined, in which discrete variables were tested using the χ2 test or Fisher exact test. RESULTS Two H. pylori tlyA variants were observed and characterized as tlyA1 and tlyA2. We noted a unique variant in the amino acid sequence 32-35 that is exclusively detected among H. pylori isolated from the Papua island. In addition, we observed that the tlyA variant had a significant association with the H. pylori density in the antral (p = 0.002). Histological analyses revealed that TlyA1 was associated with higher H. pylori density than TlyA2. However, we did not observe any significant association of tlyA with the infiltration of inflammation cells. CONCLUSIONS We observed 2 tlyA variants (tlyA1 and tlyA2). A significant association of tlyA with bacterial density suggested that tlyA plays a more significant role in the colonization process than its influence on the severity of inflammation in gastric mucosa.
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Affiliation(s)
- Adi Wasis Prakosa
- Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.,Universitas Airlangga Teaching Hospital, Surabaya, Indonesia
| | - Muhammad Miftahussurur
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga-Dr. Soetomo Teaching Hospital, Surabaya, Indonesia.,Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | | | - Langgeng Agung Waskito
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | - Dalla Doohan
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kartika Afrida Fauzia
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yudith Annisa Ayu Rezkitha
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.,Faculty of Medicine, University of Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Titong Sugihartono
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga-Dr. Soetomo Teaching Hospital, Surabaya, Indonesia
| | - Ari Fahrial Syam
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Tomohisa Uchida
- Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yoshio Yamaoka
- Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga-Dr. Soetomo Teaching Hospital, Surabaya, Indonesia.,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
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21
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Yin F, Dong J, Kang LI, Liu X. Hippo-YAP signaling in digestive system tumors. Am J Cancer Res 2021; 11:2495-2507. [PMID: 34249412 PMCID: PMC8263672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 05/23/2021] [Indexed: 06/13/2023] Open
Abstract
The Hippo pathway is an evolutionally conserved pathway and plays an important role in regulating tissue hemostasis and organ size control. Deregulation of the Hippo pathway is implicated in various human digestive system tumors. The past two decades have witnessed the discovery and elucidation of key signaling components and molecular mechanisms of the Hippo pathway. Among these, the signaling transducers YAP/TAZ are in the center of this complex network to sense and respond to extracellular cues such as cell contact, matrix stiffness and growth factors. In this review, we summarize the biological and clinical significance of Hippo-YAP signaling in the digestive system tumors, and explore the novel therapeutic strategies for targeting Hippo-YAP signaling.
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Affiliation(s)
- Feng Yin
- Department of Pathology and Anatomical Sciences, University of MissouriColumbia, Missouri, USA
| | - Jixin Dong
- Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical CenterOmaha, Nebraska, USA
| | - Liang-I Kang
- Department of Pathology and Immunology, Washington University School of MedicineSt. Louis, Missouri, USA
| | - Xiuli Liu
- Department of Pathology, Immunology and Lab Medicine, University of FloridaGainesville, Florida, USA
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22
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Olvera-Rosales LB, Cruz-Guerrero AE, Ramírez-Moreno E, Quintero-Lira A, Contreras-López E, Jaimez-Ordaz J, Castañeda-Ovando A, Añorve-Morga J, Calderón-Ramos ZG, Arias-Rico J, González-Olivares LG. Impact of the Gut Microbiota Balance on the Health-Disease Relationship: The Importance of Consuming Probiotics and Prebiotics. Foods 2021; 10:1261. [PMID: 34199351 PMCID: PMC8230287 DOI: 10.3390/foods10061261] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/25/2021] [Accepted: 05/29/2021] [Indexed: 02/07/2023] Open
Abstract
Gut microbiota is a group of microorganisms that are deposited throughout the entire gastrointestinal tract. Currently, thanks to genomic tools, studies of gut microbiota have pointed towards the understanding of the metabolism of important bacteria that are not cultivable and their relationship with human homeostasis. Alterations in the composition of gut microbiota could explain, at least in part, some epidemics, such as diabetes and obesity. Likewise, dysbiosis has been associated with gastrointestinal disorders, neurodegenerative diseases, and even cancer. That is why several studies have recently been focused on the direct relationship that these types of conditions have with the specific composition of gut microbiota, as in the case of the microbiota-intestine-brain axis. In the same way, the control of microbiota is related to the diet. Therefore, this review highlights the importance of gut microbiota, from its composition to its relationship with the human health-disease condition, as well as emphasizes the effect of probiotic and prebiotic consumption on the balance of its composition.
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Affiliation(s)
- Laura-Berenice Olvera-Rosales
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Alma-Elizabeth Cruz-Guerrero
- Departamento de Biotecnología, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Iztapalapa, Av. San Rafael Atlixco 186, Ciudad de Mexico 09340, Mexico
| | - Esther Ramírez-Moreno
- Área Académica de Nutrición, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Circuito Ex Hacienda, La Concepción S/N, Carretera Pachuca Actopan, San Agustín Tlaxiaca 42060, Hidalgo, Mexico; (E.R.-M.); (Z.-G.C.-R.)
| | - Aurora Quintero-Lira
- Área Académica de Ingeniería Agroindustrial e Ingeniería en alimentos, Instituto de Ciencias Agropecuarias, Universidad Autónoma del Estado de Hidalgo, Av. Universidad km. 1, Ex-Hacienda de Aquetzalpa, Tulancingo 43600, Hidalgo, Mexico;
| | - Elizabeth Contreras-López
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Judith Jaimez-Ordaz
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Araceli Castañeda-Ovando
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Javier Añorve-Morga
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
| | - Zuli-Guadalupe Calderón-Ramos
- Área Académica de Nutrición, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Circuito Ex Hacienda, La Concepción S/N, Carretera Pachuca Actopan, San Agustín Tlaxiaca 42060, Hidalgo, Mexico; (E.R.-M.); (Z.-G.C.-R.)
| | - José Arias-Rico
- Área Académica de Enfermería, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Circuito Ex Hacienda, La Concepción S/N, Carretera Pachuca Actopan, San Agustín Tlaxiaca 42060, Hidalgo, Mexico;
| | - Luis-Guillermo González-Olivares
- Área Académica de Química, Instituto de Ciencias Básicas e Ingeniería, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma 42184, Hidalgo, Mexico; (L.-B.O.-R.); (E.C.-L.); (J.J.-O.); (A.C.-O.); (J.A.-M.)
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23
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González MF, Díaz P, Sandoval-Bórquez A, Herrera D, Quest AFG. Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development. Int J Mol Sci 2021; 22:ijms22094823. [PMID: 34062919 PMCID: PMC8124820 DOI: 10.3390/ijms22094823] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 03/31/2021] [Accepted: 04/02/2021] [Indexed: 02/08/2023] Open
Abstract
Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.
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Affiliation(s)
- María Fernanda González
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Paula Díaz
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Alejandra Sandoval-Bórquez
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Daniela Herrera
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
| | - Andrew F. G. Quest
- Center for studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), Universidad de Chile, Santiago 8380453, Chile; (M.F.G.); (P.D.); (A.S.-B.); (D.H.)
- Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile
- Corporación Centro de Estudios Científicos de las Enfermedades Crónicas (CECEC), Santiago 7680201, Chile
- Correspondence: ; Tel.: +56-2-29786832
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24
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Tan MC, Mallepally N, Ho Q, Liu Y, El-Serag HB, Thrift AP. Dietary Factors and Gastric Intestinal Metaplasia Risk Among US Veterans. Dig Dis Sci 2021; 66:1600-1610. [PMID: 32535778 PMCID: PMC8845052 DOI: 10.1007/s10620-020-06399-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 06/03/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Studies on diet and gastric intestinal metaplasia (GIM) risk are lacking in US populations. AIM To determine the associations of dietary factors and risk of GIM among a US population with typical American diet. METHODS We analyzed data from a cross-sectional study of veterans attending primary care and endoscopy clinics at the Houston VA Medical Center. Patients completed a 110-item Block Food Frequency Questionnaire then underwent upper endoscopy with gastric mapping biopsies. We compared cases defined by GIM on ≥ 1 non-cardia gastric biopsy to controls without GIM. Associations of dietary factors and GIM were estimated using logistic regression models as odds ratios (OR) and 95% confidence intervals (CI). RESULTS Among 423 GIM cases and 1796 controls, cases were older (62.1 vs. 59.9 years) and more likely to be male (97.2% vs. 90.8%) and non-White (58.6% vs. 39.0%). GIM cases had lower fat intake (percent kcal from fat tertile 1: 43.6% vs. 33.4%) and higher carbohydrate intake (percent kcal from carbohydrate T3: 41.8% vs. 33.3%) than controls. Adjusting for age, gender, race, smoking, and Helicobacter pylori, percent kcal from carbohydrates (T3 vs. T1: OR 1.35, 95% CI 1.08-1.67), fruit intake (T3 vs. T1: OR 1.28, 95% CI 1.02-1.61), and fiber intake (T3 vs. T1: OR 1.37, 95% CI 1.04-1.80) were associated with GIM. In subgroup analyses, these associations were primarily seen in non-White patients. CONCLUSIONS Few dietary factors, including high carbohydrate intake, are associated with increased risk of GIM in US populations, independent of H. pylori or smoking.
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Affiliation(s)
- Mimi C Tan
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA.
| | | | - Quynh Ho
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA
- University of St. Thomas, Houston, TX, USA
| | - Yan Liu
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Hashem B El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
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25
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Pereira-Marques J, Ferreira RM, Machado JC, Figueiredo C. The influence of the gastric microbiota in gastric cancer development. Best Pract Res Clin Gastroenterol 2021; 50-51:101734. [PMID: 33975676 DOI: 10.1016/j.bpg.2021.101734] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 02/12/2021] [Accepted: 02/15/2021] [Indexed: 01/31/2023]
Abstract
Colonization of the stomach by Helicobacter pylori is the trigger for a series of gastric mucosal changes that culminate in gastric cancer. Infection with this bacterium is considered the major risk factor for this malignancy. The introduction of high-throughput sequencing technologies coupled to advanced computational pipelines offered an improved understanding of the microbiome, and it is now currently accepted that, besides H. pylori, the stomach harbours a complex microbial community. While it is well established that H. pylori plays a central role in gastric carcinogenesis, the significance of the non-H. pylori microbiota is yet to be clarified. This review will address the state of the art on the relationship between the gastric microbiota and gastric cancer development, and identify areas where additional research is needed before translating microbiome research into preventive and therapeutic strategies to reduce gastric cancer burden.
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Affiliation(s)
- Joana Pereira-Marques
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal.
| | - Rui M Ferreira
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal.
| | - Jose C Machado
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal; Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200 - 319, Porto, Portugal.
| | - Ceu Figueiredo
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal; Department of Pathology, Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200 - 319, Porto, Portugal.
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26
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Muñoz AB, Stepanian J, Trespalacios AA, Vale FF. Bacteriophages of Helicobacter pylori. Front Microbiol 2020; 11:549084. [PMID: 33281754 PMCID: PMC7688985 DOI: 10.3389/fmicb.2020.549084] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 10/21/2020] [Indexed: 12/12/2022] Open
Abstract
The bacterium Helicobacter pylori colonize the stomach in approximately half of the world’s population. Infection with this bacterium is associated with gastritis, peptic ulcer, adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Besides being a pathogen with worldwide prevalence, H. pylori show increasingly high antibiotic resistance rates, making the development of new therapeutic strategies against this bacterium challenging. Furthermore, H. pylori is a genetically diverse bacterium, which may be influenced by the presence of mobile genomic elements, including prophages. In this review, we analyze these issues and summarize various reports and findings related to phages and H. pylori, discussing the relationship between the presence of these elements and the genomic diversity, virulence, and fitness of this bacterium. We also analyze the state of the knowledge on the potential utility of bacteriophages as a therapeutic strategy for H. pylori.
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Affiliation(s)
- Angela B Muñoz
- Infectious Diseases Research Group, Microbiology Department, Sciences Faculty, Pontificia Universidad Javeriana, Bogotá, Colombia.,Host-Pathogen Interactions Unit, Research Institute for Medicines (iMed-ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal
| | - Johanna Stepanian
- Infectious Diseases Research Group, Microbiology Department, Sciences Faculty, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Alba Alicia Trespalacios
- Infectious Diseases Research Group, Microbiology Department, Sciences Faculty, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Filipa F Vale
- Host-Pathogen Interactions Unit, Research Institute for Medicines (iMed-ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal
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27
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Ayyagari S, Tan MC, Liu Y, El-Serag HB, Thrift AP. Use of Acid-Suppressant Medications After Diagnosis Increases Mortality in a Subset of Gastrointestinal Cancer Patients. Dig Dis Sci 2020; 65:2691-2699. [PMID: 31802383 DOI: 10.1007/s10620-019-05984-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 11/27/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Acid-suppressant medications, including proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs), are frequently prescribed and have been linked to increased risk of some gastrointestinal cancers. AIMS We examined whether post-diagnosis use of PPIs/H2RAs is associated with the risk of mortality in gastrointestinal cancer patients. METHODS We used data from patients with esophageal cancer, gastric cancer, or hepatocellular carcinomas (HCCs) in the national VA Central Cancer Registry diagnosed between 2002 and 2016. We identified PPI/H2RA prescriptions that were filled before and after cancer diagnosis and used time-dependent Cox regression models to calculate adjusted hazard ratios (HRs) and 95% CIs for mortality risk. We used a time-varying exposure to avoid immortal-time bias and a 3-month lag to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between the date of cancer diagnosis and the start of follow-up. RESULTS PPIs were used by the majority (54% post-diagnosis use) of patients. We found no association between post-diagnosis PPI use and cancer-specific mortality in esophageal adenocarcinoma (HR 0.93; 95% CI 0.84-1.02), esophageal squamous cell carcinoma (HR 0.99; 95% CI 0.87-1.12), or gastric cardia cancer (HR 1.04; 95% CI 0.89-1.22) patients. Post-diagnosis PPI use was, however, associated with the increased risk of cancer-specific mortality for patients with gastric non-cardia cancer (HR 1.50; 95% CI 1.29-1.74) and HCC (HR 1.31; 95% CI 1.23-1.40). The results were similar for associations with post-diagnosis use of H2RAs. There was no association with pre-diagnosis PPI/H2RA use. CONCLUSION Post-diagnosis PPI/H2RA use was associated with the increased mortality in gastric non-cardia cancer and HCC patients.
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Affiliation(s)
- Sanjana Ayyagari
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM307, Room 621D, Houston, TX, 77030-3498, USA
| | - Mimi C Tan
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Yan Liu
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.,Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM307, Room 621D, Houston, TX, 77030-3498, USA. .,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
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28
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Bakhti SZ, Latifi‐Navid S, Safaralizadeh R. Helicobacter pylori-related risk predictors of gastric cancer: The latest models, challenges, and future prospects. Cancer Med 2020; 9:4808-4822. [PMID: 32363738 PMCID: PMC7333836 DOI: 10.1002/cam4.3068] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 03/31/2020] [Accepted: 03/31/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co-evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori-related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry-specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high-risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age-sex-matched controls from high-risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry-specific. In addition, potential study-level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of BiologyFaculty of SciencesUniversity of Mohaghegh ArdabiliArdabilIran
| | - Saeid Latifi‐Navid
- Department of BiologyFaculty of SciencesUniversity of Mohaghegh ArdabiliArdabilIran
| | - Reza Safaralizadeh
- Department of Animal BiologyFaculty of Natural SciencesUniversity of TabrizTabrizIran
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29
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Sayed IM, Sahan AZ, Venkova T, Chakraborty A, Mukhopadhyay D, Bimczok D, Beswick EJ, Reyes VE, Pinchuk I, Sahoo D, Ghosh P, Hazra TK, Das S. Helicobacter pylori infection downregulates the DNA glycosylase NEIL2, resulting in increased genome damage and inflammation in gastric epithelial cells. J Biol Chem 2020; 295:11082-11098. [PMID: 32518160 DOI: 10.1074/jbc.ra119.009981] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 05/30/2020] [Indexed: 01/08/2023] Open
Abstract
Infection with the Gram-negative, microaerophilic bacterium Helicobacter pylori induces an inflammatory response and oxidative DNA damage in gastric epithelial cells that can lead to gastric cancer (GC). However, the underlying pathogenic mechanism is largely unclear. Here, we report that the suppression of Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase that specifically removes oxidized bases, is one mechanism through which H. pylori infection may fuel the accumulation of DNA damage leading to GC. Using cultured cell lines, gastric biopsy specimens, primary cells, and human enteroid-derived monolayers from healthy human stomach, we show that H. pylori infection greatly reduces NEIL2 expression. The H. pylori infection-induced downregulation of NEIL2 was specific, as Campylobacter jejuni had no such effect. Using gastric organoids isolated from the murine stomach in coculture experiments with live bacteria mimicking the infected stomach lining, we found that H. pylori infection is associated with the production of various inflammatory cytokines. This response was more pronounced in Neil2 knockout (KO) mouse cells than in WT cells, suggesting that NEIL2 suppresses inflammation under physiological conditions. Notably, the H. pylori-infected Neil2-KO murine stomach exhibited more DNA damage than the WT. Furthermore, H. pylori-infected Neil2-KO mice had greater inflammation and more epithelial cell damage. Computational analysis of gene expression profiles of DNA glycosylases in gastric specimens linked the reduced Neil2 level to GC progression. Our results suggest that NEIL2 downregulation is a plausible mechanism by which H. pylori infection impairs DNA damage repair, amplifies the inflammatory response, and initiates GC.
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Affiliation(s)
- Ibrahim M Sayed
- Department of Pathology, University of California San Diego, San Diego, California, USA
| | - Ayse Z Sahan
- Department of Pathology, University of California San Diego, San Diego, California, USA
| | - Tatiana Venkova
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
| | - Anirban Chakraborty
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
| | | | - Diane Bimczok
- Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA
| | - Ellen J Beswick
- Department of Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Victor E Reyes
- Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA
| | - Irina Pinchuk
- College of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Debashis Sahoo
- Department of Pediatrics, University of California San Diego, San Diego, California, USA.,Department of Computer Science and Engineering, Jacob's School of Engineering, San Diego, California, USA
| | - Pradipta Ghosh
- Department of Medicine and Cellular and Molecular Medicine, John and Rebecca Moore Cancer Center, University of California San Diego, San Diego, California, USA
| | - Tapas K Hazra
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
| | - Soumita Das
- Department of Pathology, University of California San Diego, San Diego, California, USA
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Abstract
The late 1800s Louis Pasteur and Robert Koch introduced and popularized the germ theory of disease. At that time, gastric cancer was the most common cause of cancer deaths in most countries making the stomach an early site of microbial research with a focus on gastric luminal and mucosal bacteria and the role of Boas-Oppler bacillus (Lactobacillus) in the diagnosis of gastric cancer. In the 1970s, the research focus evolved to studies of the gastric microbiome in the production of nitrosamines and included development of the Correa cascade. Interest in nitrosamine production peaked in the late 1980s and was replaced by studies of the newly described Helicobacter pylori and studies of its role in gastritis, gastric atrophy, and gastric cancer. The last decade has witnessed a rebirth in interest in the gastric microbiota as part of worldwide interest in the human microbiome. Although fungi were prominent in the studies of gastric microbiology in the nineteenth century, their potential role in disease pathogenesis has yet to be addressed using modern techniques. Overall, current studies of the gastric bacterial microbiome do not provide convincing evidence to expand the role of the gastric microbiome in cancer pathogenesis beyond what is directly attributable to the oncogenic potential of H. pylori and its role in persisting acute-on-chronic inflammation.
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Rocha GA, de Melo FF, Cabral MMDA, de Brito BB, da Silva FAF, Queiroz DMM. Interleukin-27 is abrogated in gastric cancer, but highly expressed in other Helicobacter pylori-associated gastroduodenal diseases. Helicobacter 2020; 25:e12667. [PMID: 31702083 DOI: 10.1111/hel.12667] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 10/01/2019] [Accepted: 10/03/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND IL-27 has dual roles in the immune response either stimulating Th1 or inhibiting Th17 cells. Because there is a particular link of IL-23/Th17 axis in the development of cancer and IL-27 has been considered a potential treatment for cancer, we evaluated the gastric and serum concentrations of IL-27 in two mutually exclusive Helicobacter pylori-associated diseases, gastric cancer (GC) and duodenal ulcer (DU). MATERIAL AND METHODS We prospectively studied 110 H pylori-positive patients and 40 healthy blood donors. Serum and gastric concentrations of IL-27 and cytokines of the Th1/Th17 cells were assessed by ELISA. RESULTS IL-27 was not detected in GC patients, but the cytokine concentration was very high in the patients with DU. IL-27 was also detected in the gastritis patients and in the H pylori-positive blood donors. IL27RA mRNA expression in peripheral blood mononuclear cells, evaluated by rt-PCR, was stimulated by H pylori strains. The cytokine concentration positively correlated with the Th1 and negatively with Th17 cell representative cytokine levels. Gastric IL-27 concentrations were positively correlated with increased degree of mononuclear and polymorphonuclear cells on the antral gastric mucosa of DU patients in consonance with the DU gastritis pattern. IL-12p70 and IFN-γ gastric concentrations were significantly higher in DU than in GC. Conversely, gastric concentrations of Th17 cell-associated cytokines (IL-1β, IL-6, IL-17A, IL-23, and TGF-β) were significantly higher in GC than in DU patients. CONCLUSION Although H pylori infection is able to elicit IL-27 and IL-27Rα secretion, DU and GC have diametrically opposed cytokine patterns.
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Affiliation(s)
- Gifone A Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Fabrício F de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Brazil
| | - Mônica M D A Cabral
- Department of Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Breno B de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Brazil
| | | | - Dulciene M M Queiroz
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Siegfried G, Descarpentrie J, Evrard S, Khatib AM. Proprotein convertases: Key players in inflammation-related malignancies and metastasis. Cancer Lett 2019; 473:50-61. [PMID: 31899298 PMCID: PMC7115805 DOI: 10.1016/j.canlet.2019.12.027] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 12/17/2019] [Accepted: 12/18/2019] [Indexed: 12/19/2022]
Abstract
Many cancers occur from locations of inflammation due to chronic irritation and/or infection. Tumor microenvironment contains various different inflammatory cells and mediators that orchestrate diverse neoplastic processes, including proliferation, survival, adhesion and migration. In parallel, tumor cells have adapted some of the signaling molecules used by inflammatory cells, such as selectins and chemokines as well as their receptors for invasion, extravasation and subsequently metastasis. Expression and/or activation of the majority of these molecules is mediated by the proprotein convertases (PCs); proteases expressed by both tumor cells and inflammatory cells. This review analyzes the potential role of these enzymatic system in inflammation-associated cancer impacting on the malignant and metastatic potential of cancer cells, describing the possible use of PCs as a new anti-inflammatory therapeutic approach to tumor progression and metastasis.
Proteins maturation by the proprotein convertases plays important role in inflammation-related cancer and metastasis. Protein precursors require the proprotein convertases for the induction of inflammation. Understanding of the molecular mechanism linking the proprotein convertases to inflammation will allow novel therapies. Inhibitors of the proprotein convertases constitute great potential for cancer treatment.
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Affiliation(s)
- Geraldine Siegfried
- Univ. Bordeaux, 33000, Bordeaux, France; INSERM UMR1029, 33400, Pessac, France.
| | - Jean Descarpentrie
- Univ. Bordeaux, 33000, Bordeaux, France; INSERM UMR1029, 33400, Pessac, France.
| | - Serge Evrard
- Univ. Bordeaux, 33000, Bordeaux, France; Institut Bergonié, 33076, Bordeaux, France.
| | - Abdel-Majid Khatib
- Univ. Bordeaux, 33000, Bordeaux, France; INSERM UMR1029, 33400, Pessac, France.
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Choi S, Lee JG, Lee AR, Eun CS, Han DS, Park CH. Helicobacter pylori antibody and pepsinogen testing for predicting gastric microbiome abundance. PLoS One 2019; 14:e0225961. [PMID: 31800638 PMCID: PMC6892531 DOI: 10.1371/journal.pone.0225961] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 11/16/2019] [Indexed: 01/11/2023] Open
Abstract
Background Although the high-throughput sequencing technique is useful for evaluating gastric microbiome, it is difficult to use clinically. We aimed to develop a predictive model for gastric microbiome based on serologic testing. Methods This study was designed to analyze sequencing data obtained from the Hanyang University Gastric Microbiome Cohort, which was established initially to investigate gastric microbial composition according to the intragastric environment. We evaluated the relationship between the relative abundance of potential gastric cancer-associated bacteria (nitrosating/nitrate-reducing bacteria or type IV secretion system [T4SS] protein gene-contributing bacteria) and serologic markers (IgG anti-Helicobacter pylori [HP] antibody or pepsinogen [PG] levels). Results We included 57 and 26 participants without and with HP infection, respectively. The relative abundance of nitrosating/nitrate-reducing bacteria was 4.9% and 3.6% in the HP-negative and HP-positive groups, respectively, while that of T4SS protein gene-contributing bacteria was 20.5% and 6.5% in the HP-negative and HP-positive groups, respectively. The relative abundance of both nitrosating/nitrate-reducing bacteria and T4SS protein gene-contributing bacteria increased exponentially as PG levels decreased. Advanced age (only for nitrosating/nitrate-reducing bacteria), a negative result of IgG anti-HP antibody, low PG levels, and high Charlson comorbidity index were associated with a high relative abundance of nitrosating/nitrate-reducing bacteria and T4SS protein gene-contributing bacteria. The adjusted coefficient of determination (R2) was 53.7% and 70.0% in the model for nitrosating/nitrate-reducing bacteria and T4SS protein gene-contributing bacteria, respectively. Conclusion Not only the negative results of IgG anti-HP antibody but also low PG levels were associated with a high abundance of nitrosating/nitrate-reducing bacteria and T4SS protein gene-contributing bacteria.
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Affiliation(s)
- Saemi Choi
- Department of Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Jae Gon Lee
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - A-reum Lee
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Chang Soo Eun
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- * E-mail:
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Khani S, Talebi Bezmin Abadi A, Mohabati Mobarez A. Clarithromycin-Susceptible But Virulent Helicobacter pylori Strains Infecting Iranian Patients' Stomachs. Infect Drug Resist 2019; 12:3415-3420. [PMID: 31802920 PMCID: PMC6830365 DOI: 10.2147/idr.s223602] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 10/24/2019] [Indexed: 12/15/2022] Open
Abstract
Introduction Helicobacter pylori was discovered first in the stomachs of patients with gastritis and ulcers by Marshall and Warren in 1982. This discovery majorly affected many research areas of gastroenterology. Since then, the main aim has been to eradicate this microaerophilic bacterium from the stomachs of infected subjects. Methods We studied symptomatic cases by endoscopic surgery and examined the prevalence of cagA-vacA genotypes among the H. pylori isolates. H. pylori isolated from antral biopsies of patients with gastritis and duodenal ulcer were subjected to antimicrobial susceptibility testing and PCR genotyping by using routine bacterial cultures. Clarithromycin-susceptibility profiling was done by the E-test. DNA was extracted using standard manufacturer protocols with minor modifications and cagA and vacA genotyping was done PCR. Results In our study, all strains identified as H. pylori in culture (61/81) were confirmed by PCR by amplifying a fragment of the glmM gene. Totally, 61 patients were confirmed to be positive for H. pylori and they were included in the genotyping and antibiotic-susceptibility testing. Thirteen H. pylori strains were determined to be resistant to clarithromycin. Discussion Current accumulating data indicate that both clarithromycin-resistant and susceptible isolates of H. pylori need to be screened and tracked in populations.
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Affiliation(s)
- Shadiyeh Khani
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ashraf Mohabati Mobarez
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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de Brito BB, da Silva FAF, Soares AS, Pereira VA, Santos MLC, Sampaio MM, Neves PHM, de Melo FF. Pathogenesis and clinical management of Helicobacter pylori gastric infection. World J Gastroenterol 2019; 25:5578-5589. [PMID: 31602159 PMCID: PMC6785516 DOI: 10.3748/wjg.v25.i37.5578] [Citation(s) in RCA: 161] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/14/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is influenced by several factors. The infection can be acquired by means of oral-oral or fecal-oral transmission, and the pathogen possesses various mechanisms that improve its capacity of mobility, adherence and manipulation of the gastric microenvironment, making possible the colonization of an organ with a highly acidic lumen. In addition, H. pylori presents a large variety of virulence factors that improve its pathogenicity, of which we highlight cytotoxin associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and gamma-glutamyl transpeptidase. The host immune system, mainly by means of a Th1-polarized response, also plays a crucial role in the infection course. Although most H. pylori-positive individuals remain asymptomatic, the infection predisposes the development of various clinical conditions as peptic ulcers, gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. Invasive and non-invasive diagnostic methods, each of them with their related advantages and limitations, have been applied in H. pylori detection. Moreover, bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection, and new therapy alternatives are being tested to improve H. pylori eradication. Last but not least, the development of effective vaccines against H. pylori infection have been the aim of several research studies.
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Affiliation(s)
- Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Aline Silva Soares
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Vinícius Afonso Pereira
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Maria Luísa Cordeiro Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Mariana Miranda Sampaio
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Pedro Henrique Moreira Neves
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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Lafuente Ibáñez de Mendoza I, Maritxalar Mendia X, García de la Fuente AM, Quindós Andrés G, Aguirre Urizar JM. Role of Porphyromonas gingivalis in oral squamous cell carcinoma development: A systematic review. J Periodontal Res 2019; 55:13-22. [PMID: 31529626 DOI: 10.1111/jre.12691] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 07/13/2019] [Accepted: 07/28/2019] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The target of the current systematic review is to gather and synthesize the most recent scientific information about the role of Porphyromonas gingivalis in the molecular pathways of oral squamous cell carcinoma (OSCC). BACKGROUND Oral squamous cell carcinoma is the most common malignancy of the oral cavity, with a poor prognosis and a low survival rate. Etiology is multifactorial but consumption of tobacco and alcohol is the most important risk factors. P gingivalis is a Gram-negative anaerobic bacterium commonly found in oral microbiota that has been linked to periodontal disease (PD), and recently to OSCC. However, its association with OSCC development is not well defined. MATERIAL AND METHODS A bibliographic research was carried out selecting articles published until 2019, on PubMed, Web of Science, and Scopus databases, with the keywords "Porphyromonas gingivalis," "oral cancer," "oral squamous cell carcinoma," and "periodontal pathogen." RESULTS Seventeen articles, 14 in vitro and three in animal models, were selected. Models mimicking OSCC were OSCC pre-established cell lines (11 studies), OSCC/ healthy human biopsies (three studies), and animals with OSCC (three studies). P gingivalis strains used to cause infection in these studies were ATCC 33277, 381, and W83. CONCLUSIONS Porphyromonas gingivalis could play an important role in OSCC development and could be involved in three different stages: epithelial-mesenchymal transition of malignant cells, neoplastic proliferation, and tumor invasion. Current findings emphasize the convenience of treatment and control approaches of PD as part of the primary prevention of OSCC.
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Affiliation(s)
| | | | | | - Guillermo Quindós Andrés
- Department of Immunology, Microbiology and Parasitology, University of the Basque Country (UPV/EHU), Leioa, Vizcaya, Spain
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Sokolova O, Naumann M. Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis. Curr Top Microbiol Immunol 2019; 421:107-137. [PMID: 31123887 DOI: 10.1007/978-3-030-15138-6_5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Over the last years, intensive investigations in molecular biology and cell physiology extended tremendously the knowledge about the association of inflammation and cancer. In frame of this paradigm, the human pathogen Helicobacter pylori triggers gastritis and gastric ulcer disease, and contributes to the development of gastric cancer. Mechanisms, by which the bacteria-induced inflammation in gastric mucosa leads to intestinal metaplasia and carcinoma, are represented in this review. An altered cell-signaling response and increased production of free radicals by epithelial and immune cells account for the accumulation of DNA damage in gastric mucosa, if infection stays untreated. Host genetics and environmental factors, especially diet, can accelerate the process, which offers the opportunity of intervention based on a balanced nutrition. It is supposed that inflammation might influence stem- or progenitor cells in gastric tissue predisposing for metaplasia or tumor relapse. Herein, DNA is strongly mutated and labile, which restricts therapy options. Thus, the understanding of the mechanisms that underlie gastric carcinogenesis will be of preeminent importance for the development of strategies for screening and early detection. As most gastric cancer patients face late-stage disease with a poor overall survival, the development of multi-targeted therapeutic intervention strategies is a major challenge for the future.
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Affiliation(s)
- Olga Sokolova
- Institute of Experimental Internal Medicine, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
| | - Michael Naumann
- Institute of Experimental Internal Medicine, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany
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Jin RU, Mills JC. The cyclical hit model: how paligenosis might establish the mutational landscape in Barrett's esophagus and esophageal adenocarcinoma. Curr Opin Gastroenterol 2019; 35:363-370. [PMID: 31021922 PMCID: PMC11960809 DOI: 10.1097/mog.0000000000000540] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW In this review, we explore a paligenosis-based model to explain Barrett's esophagus development and progression: 'the cyclical hit model.' RECENT FINDINGS Genomic analyses have highlighted the high mutational burden of esophageal adenocarcinoma, Barrett's esophagus, and even normal esophageal epithelium. Somatic mutations in key genes including TP53 occur early in the neoplastic progression sequence of Barrett's esophagus, whereas chromosomal amplification resulting in oncogene activation occurs as a critical late event. Paligenosis is a shared injury response mechanism characterized by activation of autophagy, expression of progenitor markers, and increased mTORC signaling-induced cell-cycle reentry. In the setting of chronic injury/inflammation, cycles of paligenosis may allow accumulation of mutations until eventually the mutational burden, in concert perhaps with mutations in key driver oncogenes, finally alters the cell's ability to redifferentiate, leading to the emergence of a potential neoplastic clone. SUMMARY Under conditions of chronic gastroesophageal refluxate exposure, the normal esophageal squamous epithelium might undergo multiple cycles of paligenosis, allowing initially silent mutations to accumulate until key events impart mutant clones with an oncogenic survival advantage.
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Affiliation(s)
- Ramon U. Jin
- Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Jason C. Mills
- Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
- Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA
- Depart-Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA
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Miftahussurur M, Waskito LA, Syam AF, Nusi IA, Wibawa IDN, Rezkitha YAA, Siregar G, Yulizal OK, Akil F, Uwan WB, Simanjuntak D, Waleleng JB, Saudale AMJ, Yusuf F, Maulahela H, Richardo M, Rahman A, Namara YS, Sudarmo E, Adi P, Maimunah U, Setiawan PB, Fauzia KA, Doohan D, Uchida T, Lusida MI, Yamaoka Y. Analysis of risks of gastric cancer by gastric mucosa among Indonesian ethnic groups. PLoS One 2019; 14:e0216670. [PMID: 31071187 PMCID: PMC6508733 DOI: 10.1371/journal.pone.0216670] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 04/25/2019] [Indexed: 12/16/2022] Open
Abstract
Indonesia is a big country with multiethnic populations whose gastric cancer risks have not been elucidated. We performed a nationwide survey and obtained histological specimens from 1053 individuals in 19 cities across the country. We examined the gastric mucosa, the topography, the atrophic gastritis risk factors, and the gastric cancer risk scores. Almost half (46.1%) of the patients with dyspeptic symptoms had histological abnormalities; chronic (36.3%) and atrophic gastritis (28.9%) being the most frequent. Individuals of the Timor ethnicity had the highest prevalence of acute (52.6%) and chronic gastritis (68.4%), even those negative for H. pylori. Our topographic analysis showed the majority of patients had predominantly antral acute and chronic gastritis. A multivariate logistic regression model showed age (Odds ratio [OR], 1.107), Timor ethnicity (OR, 8.531), and H. pylori infection (OR, 22.643) as independent risk factors for presence of atrophic gastritis. In addition, the gastric cancer risk score was highest in those from Timor, Papuan, and Bugis ethnic populations. Overall, Indonesia is a low-risk gastric cancer country. However, several ethnic groups displayed severe gastric mucosa symptoms suggesting policy makers should focus on those ethnic groups to perform gastric cancer screenings and to eradicate H. pylori.
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Affiliation(s)
- Muhammad Miftahussurur
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Indonesia
- Institute of Tropical Diseases, Universitas Airlangga, Indonesia
- * E-mail: (YY); (MM)
| | - Langgeng Agung Waskito
- Institute of Tropical Diseases, Universitas Airlangga, Indonesia
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Ari Fahrial Syam
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Iswan Abbas Nusi
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Indonesia
| | - I Dewa Nyoman Wibawa
- Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine University of Udayana, Denpasar, Indonesia
| | - Yudith Annisa Ayu Rezkitha
- Institute of Tropical Diseases, Universitas Airlangga, Indonesia
- Faculty of Medicine, University of Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Gontar Siregar
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, Indonesia
| | - OK Yulizal
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, Indonesia
| | - Fardah Akil
- Center of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | - Willy Brodus Uwan
- Department of Internal Medicine, Santo Antonius Hospital, Pontianak, Indonesia
| | - David Simanjuntak
- Department of Internal Medicine, Yowari Hospital, Jayapura, Indonesia
| | - Jimmy Bradley Waleleng
- Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sam Ratulangi, Prof. Dr. RD Kandou Hospital, Manado, Indonesia
| | | | - Fauzi Yusuf
- Division of Gastroenterohepatology, Department of Internal Medicine, Dr. Zainoel Abidin General Hospital, Banda Aceh, Indonesia
| | - Hasan Maulahela
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Marselino Richardo
- Department of Internal Medicine, Merauke City General Hospital, Merauke, Indonesia
| | - Abdul Rahman
- Department of Internal Medicine, Kolaka General Hospital, Kolaka, Indonesia
| | - Yoma Sari Namara
- Department of Internal Medicine, Anutapura General Hospital, Palu, Indonesia
| | - Eko Sudarmo
- Department of Internal Medicine, Dr. Hasan Busori General hospital, Ternate, Indonesia
| | - Pangestu Adi
- Institute of Tropical Diseases, Universitas Airlangga, Indonesia
| | - Ummi Maimunah
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Indonesia
| | - Poernomo Boedi Setiawan
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Indonesia
| | - Kartika Afrida Fauzia
- Institute of Tropical Diseases, Universitas Airlangga, Indonesia
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Dalla Doohan
- Institute of Tropical Diseases, Universitas Airlangga, Indonesia
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Tomohisa Uchida
- Department of Molecular Pathology, Oita University Faculty of Medicine, Hasama-machi, Yufu-City, Oita, Japan
| | | | - Yoshio Yamaoka
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Indonesia
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, United States of America
- Global Oita Medical Advanced Research Center for Health, Hasama-machi, Yufu-City, Oita, Japan
- * E-mail: (YY); (MM)
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Auttajaroon J, Chotivitayatarakorn P, Yamaoka Y, Vilaichone RK. CYP2C19 Genotype, CagA Genotype and Antibiotic Resistant
Strain of Helicobacter pylori Infection. Asian Pac J Cancer Prev 2019; 20:1243-1247. [PMID: 31030500 PMCID: PMC6948911 DOI: 10.31557/apjcp.2019.20.4.1243] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background: H. pylori is a class I carcinogen and major cause of gastric cancer. Few previous studies reported
relationship between H. pylori infection, CYP2C19 genotype and functional dyspepsia (FD) subtype. The aim of this
study was to determine relationship between CYP2C19 genotype and FD subtype patients(host factor) with antibiotic
resistant strains of H. pylori infection and CagA genotype(bacterial factor). Methods: FD patients who were investigated
with gastroscopy at Thammasat University Hospital, Thailand during March 2017-November 2017 were enrolled. Two
antral gastric biopsies were obtained for rapid urease test, E-test and cultures. CagA genotypes (CagA1a and CagA2a)
were determined by PCR and CYP2C19 genotype was determined by PCR-RFLP. FD patients were categorized as
epigastric pain syndrome(EPS) and postprandial distress syndrome (PDS). Results: 93 FD patients with H. pylori
infection were enrolled (37 male, 56 female, mean age 54.5 years). There were 33 patients with EPS and 60 patients
with PDS. CYP2C19 genotype revealed 55.9% rapid metabolizer (RM), 40.9% intermediate metabolizer (IM) and
3.2% poor metabolizer (PM) genotypes. Antibiotics susceptibility tests demonstrated 62.8% resistant to metronidazole,
12.9% resistant to clarithromycin and 27.1% resistant to fluoroquinolone. CagA 1a and CagA 2a were demonstrated
in 6 patients(11.5%) and 46 patients(88.5%). CagA2a genotype was more prevalent in PDS than EPS patients
(94.3%vs.76.5%; P =0.08) without significance. In intermediate metabolizer (IM), CagA2a genotype was significant
higher in PDS than EPS(100% vs.25%; P=0.004). Conclusions: PDS, CYP2C19 RM genotype and CagA 2a gene of
H. pylori infection were the predominant type of FD in Thailand. Metronidazole remain the most common antibiotic
resistant strain of H. pylori infection in FD patients. PDS (host factor) was significantly related to CagA2a genotype
(bacterial factors) only in patients with intermediate metabolizer. Appropriate dose of proton pump inhibitor (PPI) and
correct regimens for H. pylori eradication in FD patients should be consider to improve clinical outcomes.
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Affiliation(s)
- Jeerayuth Auttajaroon
- Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Thammasat University Hospital, Pathumthani, Thailand.
| | - Peranart Chotivitayatarakorn
- Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Thammasat University Hospital, Pathumthani, Thailand. ,National Gastric Cancer and Gastrointestinal Diseases Research Center (NGGC), Department of Medicine,Pathumthani, Thailand.,Chulabhorn International College of Medicine (CICM) at Thammasat University, Pathumthani, Thailand
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita, Japan
| | - Ratha-Korn Vilaichone
- Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Thammasat University Hospital, Pathumthani, Thailand. ,National Gastric Cancer and Gastrointestinal Diseases Research Center (NGGC), Department of Medicine,Pathumthani, Thailand.,Chulabhorn International College of Medicine (CICM) at Thammasat University, Pathumthani, Thailand
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Rugge M, Sugano K, Scarpignato C, Sacchi D, Oblitas WJ, Naccarato AG. Gastric cancer prevention targeted on risk assessment: Gastritis OLGA staging. Helicobacter 2019; 24:e12571. [PMID: 30773732 DOI: 10.1111/hel.12571] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/08/2019] [Accepted: 01/10/2019] [Indexed: 12/24/2022]
Abstract
Gastric cancer (GC) ranks among the most lethal epithelial malignancies, and its striking mortality rate prompts a global prevention strategy. Helicobacter pylori (H. pylori) gastritis is the main GC promoter, and the 2014 Global Kyoto conference recognized H. pylori gastritis as a (treatable) infectious disease. It is therefore plausible that any large-scale intervention for H. pylori eradication would result in cleansing the world of the fifth cause of cancer-related death. Atrophic gastritis is the cancerization field in which GCs (both intestinal and diffuse histotypes) mainly develop. Discontinuing the inflammatory cascade triggered by H. pylori is tantamount to preventing GC. For patients (still infected or eradicated) who have already developed gastric atrophy, the severity/topography of the atrophic changes correlates with their cancer risk. Gastritis OLGA (Operative Link for Gastritis Assessment) staging consistently ranks the atrophy-associated cancer risk, providing a solid clinical/biological rationale for establishing patient-specific surveillance programs. By combining primary and secondary prevention strategies, gastric cancer is a preventable disease.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy.,Veneto Tumor Registry (RTV), Veneto Regional Authority, Padova, Italy
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Carmelo Scarpignato
- Department of Medicine and Surgery, Clinical Pharmacology and Pathophysiology Unit, School of Medicine and Dentistry, University of Parma, Parma, Italy
| | - Diana Sacchi
- Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy
| | | | - Antonio Giuseppe Naccarato
- Department of Translational Research and of New Surgical and Medical Technologies, Pathology Section, University of Pisa, Pisa, Italy
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42
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Zou D, Xu L, Li H, Ma Y, Gong Y, Guo T, Jing Z, Xu X, Zhang Y. Role of abnormal microRNA expression in Helicobacter pylori associated gastric cancer. Crit Rev Microbiol 2019; 45:239-251. [PMID: 30776938 DOI: 10.1080/1040841x.2019.1575793] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Epidemiological studies have shown that Helicobacter pylori (HP) infection is a risk factor for gastric cancer (GC). HP infection may induce the release of pro-inflammatory mediators, and abnormally increase the level of reactive oxygen species (ROS), nitric oxide (NO), and cytokines in mucosal epithelial cells of the stomach. However, the specific mechanism underlying the pathogenesis of HP-associated GC is still poorly understood. Recent studies have revealed that abnormal microRNA expression may affect the proliferation, differentiation, and apoptosis of mucosal epithelial cells of the stomach to further influence GC occurrence, development, and metastasis. Herein, we summarize the role of abnormal microRNAs in the regulation of HP-associated GC progression. Abnormal microRNA expression in HP-positive GC may be a biomarker for GC diagnosis, occurrence, and development as well as its targeted treatment and prognosis.
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Affiliation(s)
- Dan Zou
- a The First laboratory of cancer institute , First Hospital of China Medical University , Shenyang , China
| | - Ling Xu
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China
| | - Heming Li
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China.,c Department of Oncology , Affiliated Zhongshan Hospital of Dalian University , Dalian , China
| | - Yanju Ma
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China.,d Department of Medical Oncology , Cancer Hospital of China Medical University , Shenyang , China
| | - Yuehua Gong
- e Department of Tumor Etiology and Screening Department of Cancer Institute and General Surgery, First Hospital of China Medical University , Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department , Shenyang , China
| | - Tianshu Guo
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China
| | - Zhitao Jing
- f Department of Neurosurgery , First Hospital of China Medical University , Shenyang , China
| | - Xiuying Xu
- g Department of Gastroenterology , First Hospital of China Medical University , Shenyang , China
| | - Ye Zhang
- a The First laboratory of cancer institute , First Hospital of China Medical University , Shenyang , China
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Abstract
PURPOSE OF REVIEW This review integrates the new thinking about relationships between gastric cancer and intestinal metaplasia/pseudopyloric metaplasia (SPEM). We address whether recent studies have closed or widened the knowledge gap regarding gastric cancer pathogenesis in mice or humans. RECENT FINDINGS Recent studies in mouse models have provided a variety of new insights into the cellular origin and progression of events resulting in gastric cancer. Many suggest a direct transformation from intestinal metaplasia/pseudopyloric metaplasia/SPEM to gastric cancer. However, results from different investigator and models are conflicting and often describe events not present in studies in humans. SUMMARY Both Helicobacter pylori-associated and autoimmune gastritis may produce gastric atrophy with extensive intestinal metaplasia and an abnormal gastric microbiome. However, only H. pylori gastritis carries a risk for adenocarcinoma. The differences reported with mouse models can best be explained as the results of different models of regeneration and repair rather than as models of gastric cancer. Overall, the data remains consistent with the original hypothesis that gastric cancer results from increased genetic instability of gastric stem cells rather than a direct transition from metaplasia to cancer. Intestinal metaplasia, pseudopyloric metaplasia, and SPEM have all been falsely accused based on guilt by association.
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45
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Bubić A, Mrnjavac N, Stuparević I, Łyczek M, Wielgus-Kutrowska B, Bzowska A, Luić M, Leščić Ašler I. In the quest for new targets for pathogen eradication: the adenylosuccinate synthetase from the bacterium Helicobacter pylori. J Enzyme Inhib Med Chem 2018; 33:1405-1414. [PMID: 30191734 PMCID: PMC6136348 DOI: 10.1080/14756366.2018.1506773] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Adenylosuccinate synthetase (AdSS) is an enzyme at regulatory point of purine metabolism. In pathogenic organisms which utilise only the purine salvage pathway, AdSS asserts itself as a promising drug target. One of these organisms is Helicobacter pylori, a wide-spread human pathogen involved in the development of many diseases. The rate of H. pylori antibiotic resistance is on the increase, making the quest for new drugs against this pathogen more important than ever. In this context, we describe here the properties of H. pylori AdSS. This enzyme exists in a dimeric active form independently of the presence of its ligands. Its narrow stability range and pH-neutral optimal working conditions reflect the bacterium’s high level of adaptation to its living environment. Efficient inhibition of H. pylori AdSS with hadacidin and adenylosuccinate gives hope of finding novel drugs that aim at eradicating this dangerous pathogen.
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Affiliation(s)
- Ante Bubić
- a Division of Physical Chemistry , Ruđer Bošković Institute , Zagreb , Croatia
| | - Natalia Mrnjavac
- a Division of Physical Chemistry , Ruđer Bošković Institute , Zagreb , Croatia
| | - Igor Stuparević
- b Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology , University of Zagreb , Zagreb , Croatia
| | - Marta Łyczek
- c Division of Biophysics, Institute of Experimental Physics, Faculty of Physics , University of Warsaw , Warsaw , Poland.,d Department of Bacterial Genetics, Faculty of Biology, Institute of Microbiology , University of Warsaw , Warsaw , Poland
| | - Beata Wielgus-Kutrowska
- c Division of Biophysics, Institute of Experimental Physics, Faculty of Physics , University of Warsaw , Warsaw , Poland
| | - Agnieszka Bzowska
- c Division of Biophysics, Institute of Experimental Physics, Faculty of Physics , University of Warsaw , Warsaw , Poland
| | - Marija Luić
- a Division of Physical Chemistry , Ruđer Bošković Institute , Zagreb , Croatia
| | - Ivana Leščić Ašler
- a Division of Physical Chemistry , Ruđer Bošković Institute , Zagreb , Croatia
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46
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Status (on/off) of oipA gene: their associations with gastritis and gastric cancer and geographic origins. Arch Microbiol 2018; 201:93-97. [PMID: 30255200 DOI: 10.1007/s00203-018-1580-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 08/30/2018] [Accepted: 09/24/2018] [Indexed: 02/07/2023]
Abstract
Virulence factors of H. pylori, such as outer inflammatory protein A (oipA), are closely involved in the development of gastric diseases such as chronic gastritis and gastric cancer. The functional status of oipA is regulated by a repair mechanism based on CT dinucleotide repeats that influence the reading frame, thus granting the gene a functional or nonfunctional status; in other words, the functional status of the oipA gene seems to be associated with the development of gastric diseases. This study sought to detect the presence of the oipA gene and to determine its functional status in patients with gastric diseases. We analyzed 516 biopsy samples (101 with normal gastric tissue, 365 with chronic gastritis, and 50 with gastric cancer). The presence of oipA was determined by PCR, and the gene status was determined using sequencing reactions. The oipA gene was found to be associated with the development of chronic gastritis, and the "on" status of the gene was the most frequent in patients with gastric cancer who were from Western countries. The CT repeats revealed geographic characteristics, but it is the functional status of the oipA gene that seems to be involved in the development of gastric diseases and in the development of gastric cancer in particular.
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47
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Talebi Bezmin Abadi A, Yamaoka Y. Helicobacter pylori therapy and clinical perspective. J Glob Antimicrob Resist 2018; 14:111-117. [PMID: 29581076 DOI: 10.1016/j.jgar.2018.03.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 03/06/2018] [Accepted: 03/16/2018] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori induces chronic gastritis and duodenal ulcer in a small fraction of the colonised population. Three decades after the discovery of H. pylori and disclosure of an urgent need for eliminating the bacterium in patients, it seems that we are still in the first steps of dealing with this mysterious organism. Treatment of H. pylori is a complex dilemma for clinicians, a repeating sentence by many scientists who spend years on this research topic. Apart from many modifications in initial first-line treatment of H. pylori, gastroenterologists are unable to overcome the problem of therapeutic failure. Choosing the best regimen in any region depends on many factors, which have been the focus of many randomised clinical trials. A potential increase in efficacy of future therapies may be influenced by adding the novel potassium-competitive acid blocker vonoprazan. Undeniably, in-depth analysis is necessary to propose more effective therapeutic regimens. Meanwhile, we recommend the performance of antimicrobial susceptibility testing before any antimicrobial prescription.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Yoshio Yamaoka
- Department of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA; Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
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48
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Gantuya B, Bolor D, Oyuntsetseg K, Erdene-Ochir Y, Sanduijav R, Davaadorj D, Tserentogtokh T, Azzaya D, Uchida T, Matsuhisa T, Yamaoka Y. New observations regarding Helicobacter pylori and gastric cancer in Mongolia. Helicobacter 2018; 23:e12491. [PMID: 29882322 PMCID: PMC6039254 DOI: 10.1111/hel.12491] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The incidence and mortality of gastric cancer in Mongolia is among the highest in the world. METHODS This was a case-control study in which upper gastrointestinal endoscopy, gastric histology, Helicobacter pylori testing, and risk factor questionnaires were obtained. Histologic subtypes were determined by Lauren's classification. RESULTS We enrolled 45 gastric cancer and 108 non-gastric cancer patients. Gastric cancers were located in upper part of stomach in 53.3%, main gastric body in 37.8%, and lower part of stomach in 8.9%. The majority (60%) were diffuse type, followed by intestinal type (36.7%) and indeterminate type (3.3%). H. pylori infections were CagA positive in 100% with cancer vs 81% without cancer (P = .02). The majority of CagA was non-East Asian type (95% with cancer and 94.1% without cancer). Cancer patients had typically related with excessive use of salt, hot beverages, tobacco smoking, and low ingestion of fruits. CONCLUSION The characteristic topography of gastric cancer in Mongolia being in the gastric corpus differed from East Asian countries and was more similar to western countries. The risk factors for gastric cancer in Mongolia were similar to other high-risk areas (ie, H. pylori infection, excessive use of salt, tobacco smoking, and low ingestion of fruits).
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Affiliation(s)
- Boldbaatar Gantuya
- Department of Environmental and Preventive Medicine, Oita University of Medicine, Yufu, Japan,Department of Gastroenterology, Mongolian National University of Medical sciences, Ulaanbaatar, Mongolia
| | - Dashdorj Bolor
- Department of Endoscopy, National Cancer Center, Ulaanbaatar, Mongolia
| | - Khasag Oyuntsetseg
- Department of Gastroenterology, Mongolian National University of Medical sciences, Ulaanbaatar, Mongolia
| | - Yansan Erdene-Ochir
- Department of General surgery, National Cancer Center, Ulaanbaatar, Mongolia
| | - Ruvjir Sanduijav
- Department of Oncology, Mongolian National University of Medical sciences, Ulaanbaatar, Mongolia
| | - Duger Davaadorj
- Department of Gastroenterology, Mongolian National University of Medical sciences, Ulaanbaatar, Mongolia
| | - Tegshee Tserentogtokh
- Department of Gastroenterology, Mongolian National University of Medical sciences, Ulaanbaatar, Mongolia
| | - Dashdorj Azzaya
- Department of Environmental and Preventive Medicine, Oita University of Medicine, Yufu, Japan
| | - Tomohisa Uchida
- Department of Molecular Pathology, Oita University of Medicine
| | - Takeshi Matsuhisa
- Department of Gastroenterology, Tama-Nagayama University Hospital of Nippon Medical School
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University of Medicine, Yufu, Japan,Department of Medicine, Gastroenterology and Hepatology section, Baylor College of Medicine, Houston, Texas77030, USA
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Cisarò F, Pizzol A, Pinon M, Calvo PL. Diagnosis and treatment of Helicobacter pylori in the pediatric population. Minerva Pediatr 2018; 70:476-487. [PMID: 30021412 DOI: 10.23736/s0026-4946.18.05346-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Although about 35 years have elapsed since the discovery of the Helicobacter pylori, its diagnosis and the choice of optimal eradication therapy are still to be defined. Over time, there has been an increase in interest, publications, recommendations and guidelines. Moreover, management of the disease in pediatric subjects differs somewhat to that of adults and requires a more delicate approach leading to alternative strategies for both diagnosis and treatment. Which patient should be investigated for H. pylori, when to perform noninvasive or invasive tests, what are the proper therapeutic options and best antibiotics regimen to eradicate the infection are practices changing with evidences through time. Therefore, an updated guideline was published by the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) in 2017. The aim of this review is to highlight what is new and what differs between adult and pediatric population regarding the management of H. pylori infection after the ESPGHAN/NASPGHAN guidelines, enriched with updates from literature reviews published over the last two years.
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Affiliation(s)
- Fabio Cisarò
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Antonio Pizzol
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy -
| | - Michele Pinon
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Pier Luigi Calvo
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
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50
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Tan MC, Graham DY. Proton pump inhibitor therapy after Helicobacter pylori eradication may increase the risk of gastric cancer. BMJ Evid Based Med 2018; 23:111-112. [PMID: 29599181 PMCID: PMC6916725 DOI: 10.1136/bmjebm-2018-110935] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/09/2018] [Indexed: 01/22/2023]
Affiliation(s)
- Mimi Chang Tan
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas, USA
| | - David Y Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas, USA
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