{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:39:11Z","timestamp":1760240351982,"version":"build-2065373602"},"reference-count":104,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,5,18]],"date-time":"2019-05-18T00:00:00Z","timestamp":1558137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Helicobacter pylori (H. pylori) represents an independent risk factor for Gastric Cancer (GC). First Degree Relatives (FDR) of GC subjects and Autoimmune Gastritis (AG) patients are both at increased risk for GC. H. pylori genetic heterogeneity within the gastric niche of FDR and AG individuals has been little explored. To understand whether they exploit an increased H. pylori stability and virulence, 14 AG, 25 FDR, 39 GC and 13 dyspeptic patients (D) were investigated by a cultural PCR-based approach characterizing single colonies-forming-units. We chose three loci within the Cytotoxin-associated gene-A Pathogenicity Island (CagPAI) (cagA,cagE,virB11), vacA, homA and homB as markers of virulence with reported association to GC. Inflammatory\/precancerous lesions were staged according to Sydney System. When compared to D, FDR, similarly to GC patients, were associated to higher atrophy (OR = 6.29; 95% CI:1.23\u201331.96 in FDR; OR = 7.50; 95% CI:1.67\u201333.72 in GC) and a lower frequency of mixed infections (OR = 0.16; 95% CI:0.03\u20130.81 in FDR; OR = 0.10; 95% CI:0.02\u20130.48 in GC). FDR presented also an increased neutrophil infiltration (OR = 7.19; 95% CI:1.16\u201344.65). Both FDR and GC carried a higher proportion of CagPAI+vacAs1i1mx+homB+ profiles (OR = 2.71; 95% CI: 1.66\u20134.41 and OR = 3.43; 95% CI: 2.16\u20135.44, respectively). Conversely, AG patients presented a lower frequency of subtypes carrying a stable CagPAI and vacAs1i1mx. These results underline different H. pylori plasticity in FDR and AG individuals, and thus, a different host-bacterium interaction capacity that should be considered in the context of eradication therapies.<\/jats:p>","DOI":"10.3390\/pathogens8020065","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T11:05:07Z","timestamp":1558350307000},"page":"65","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Differential Helicobacter pylori Plasticity in the Gastric Niche of Subjects at Increased Gastric Cancer Risk"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5832-2895","authenticated-orcid":false,"given":"Mariateresa","family":"Casarotto","sequence":"first","affiliation":[{"name":"Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7083-8392","authenticated-orcid":false,"given":"Chiara","family":"Pratesi","sequence":"additional","affiliation":[{"name":"Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ettore","family":"Bidoli","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Maiero","sequence":"additional","affiliation":[{"name":"Oncological Gastroenterology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Magris","sequence":"additional","affiliation":[{"name":"Oncological Gastroenterology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-3054","authenticated-orcid":false,"given":"Agostino","family":"Steffan","sequence":"additional","affiliation":[{"name":"Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Basaglia","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Azienda per l\u2019Assistenza Sanitaria n. 5 Friuli Occidentale, 33170 Pordenone, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6010-0976","authenticated-orcid":false,"given":"Vincenzo","family":"Canzonieri","sequence":"additional","affiliation":[{"name":"Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6100-9373","authenticated-orcid":false,"given":"Valli","family":"De Re","sequence":"additional","affiliation":[{"name":"Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2020-222X","authenticated-orcid":false,"given":"Renato","family":"Cannizzaro","sequence":"additional","affiliation":[{"name":"Oncological Gastroenterology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0608-9766","authenticated-orcid":false,"given":"Stefania","family":"Zanussi","sequence":"additional","affiliation":[{"name":"Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1172\/JCI20925","article-title":"Helicobacter pylori persistence: Biology and disease","volume":"113","author":"Blaser","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1172\/JCI38605","article-title":"Coadaptation of Helicobacter pylori and humans: Ancient history, modern implications","volume":"119","author":"Atherton","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_3","unstructured":"IARC (1994). Infection with Helicobacter pylori. Monogr. Eval. Carcinog. Risks Hum., 61, 177\u2013240."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1002\/ijc.21731","article-title":"The global health burden of infection-associated cancers in the year 2002","volume":"118","author":"Parkin","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1751-2980.2011.00550.x","article-title":"The gastric precancerous cascade","volume":"13","author":"Correa","year":"2012","journal-title":"J. Dig. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1053\/j.gastro.2009.01.073","article-title":"Helicobacter pylori in health and disease","volume":"136","author":"Cover","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1523-5378.2012.00954.x","article-title":"A potential association between Helicobacter pylori CagA EPIYA and multimerization motifs with cytokeratin 18 cleavage rate during early apoptosis","volume":"17","author":"Saberi","year":"2012","journal-title":"Helicobacter"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.tim.2013.09.004","article-title":"Modulation of autophagy by Helicobacter pylori and its role in gastric carcinogenesis","volume":"21","author":"Greenfield","year":"2013","journal-title":"Trends Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nrmicro1658","article-title":"Helicobacter pylori evolution and phenotypic diversification in a changing host","volume":"5","author":"Suerbaum","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1093\/jnci\/djm120","article-title":"Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions","volume":"99","author":"Plummer","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/ajg.2011.1","article-title":"Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: A long-term follow-up in a high-risk area in Spain","volume":"106","author":"Figueiredo","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4251\/wjgo.v8.i1.40","article-title":"Helicobacter pylori infection and gastric carcinoma: Not all the strains and patients are alike","volume":"8","author":"Figura","year":"2016","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1097\/MEG.0000000000000414","article-title":"Histological variety of gastric carcinoma and Helicobacter pylori cagA and vacA polymorphism","volume":"27","author":"Figura","year":"2015","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2119\/molmed.2013.00076","article-title":"Differential proteomics of Helicobacter pylori associated with autoimmune atrophic gastritis","volume":"20","author":"Repetto","year":"2014","journal-title":"Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1080\/14789450.2017.1331739","article-title":"Application of proteomics to the study of Helicobacter pylori and implications for the clinic","volume":"14","author":"Bernardini","year":"2017","journal-title":"Expert Rev. Proteom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1086\/515606","article-title":"Acid-tolerance response in Helicobacter pylori and differences between cagA+ and cagA- strains","volume":"178","author":"Karita","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1056\/NEJMra020542","article-title":"Helicobacter pylori infection","volume":"347","author":"Suerbaum","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1083-4389.2004.00224.x","article-title":"Inactivation of Helicobacter pylori cagA gene affects motility","volume":"9","author":"Figura","year":"2004","journal-title":"Helicobacter"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1179\/joc.2004.16.5.504","article-title":"Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates","volume":"16","author":"Basaglia","year":"2004","journal-title":"J. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1111\/j.1469-0691.2004.00985.x","article-title":"The predictive value of Helicobacter pylori in-vitro metronidazole resistance","volume":"10","author":"Tomasini","year":"2004","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1128\/JCM.41.3.976-980.2003","article-title":"Heterogeneity of cag genotypes in Helicobacter pylori isolates from human biopsy specimens","volume":"41","author":"Tomasini","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1574-6968.2001.tb10828.x","article-title":"Heterogeneity of Helicobacter pylori cag genotypes in experimentally infected mice","volume":"203","author":"Sozzi","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1572-0241.1998.00375.x","article-title":"Atrophic gastritis and intestinal metaplasia in Helicobacter pylori infection: The role of CagA status","volume":"93","author":"Sozzi","year":"1998","journal-title":"Am. J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.lab.2005.06.010","article-title":"Heterogeneity of cag genotypes and clinical outcome of Helicobacter pylori infection","volume":"146","author":"Sozzi","year":"2005","journal-title":"J. Lab. Clin. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1128\/CMR.00011-10","article-title":"Helicobacter pylori and gastric cancer: Factors that modulate disease risk","volume":"23","author":"Wroblewski","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1128\/JCM.01501-09","article-title":"Epidemiological link between gastric disease and polymorphisms in VacA and CagA","volume":"48","author":"Jang","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10566","DOI":"10.1016\/S0021-9258(17)34097-8","article-title":"Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains","volume":"269","author":"Cover","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1053\/j.gastro.2007.06.056","article-title":"A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer","volume":"133","author":"Rhead","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1053\/j.gastro.2008.03.041","article-title":"Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms","volume":"135","author":"Basso","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.15171\/bi.2017.08","article-title":"Pleiotropic cytotoxicity of VacA toxin in host cells and its impact on immunotherapy","volume":"7","author":"Fahimi","year":"2017","journal-title":"Bioimpacts"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1086\/592166","article-title":"Evaluation of the clinical significance of homB, a novel candidate marker of Helicobacter pylori strains associated with peptic ulcer disease","volume":"198","author":"Oleastro","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1128\/JCM.00293-09","article-title":"homB status of Helicobacter pylori as a novel marker to distinguish gastric cancer from duodenal ulcer","volume":"47","author":"Jung","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1128\/JCM.00947-11","article-title":"Helicobacter pylori homB, but not cagA, is associated with gastric cancer in Iran","volume":"49","author":"Rafiei","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1128\/IAI.00123-06","article-title":"Identification of markers for Helicobacter pylori strains isolated from children with peptic ulcer disease by suppressive subtractive hybridization","volume":"74","author":"Oleastro","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1146\/annurev.pathol.1.110304.100125","article-title":"The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases","volume":"1","author":"Atherton","year":"2006","journal-title":"Annu. Rev. Pathol."},{"key":"ref_36","first-page":"42","article-title":"Genetic host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms","volume":"1869","author":"Mommersteeg","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.ijmm.2015.03.002","article-title":"Analysis of a single Helicobacter pylori strain over a 10-year period in a primate model","volume":"305","author":"Liu","year":"2015","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4668","DOI":"10.1128\/IAI.72.8.4668-4679.2004","article-title":"Chronic Helicobacter pylori infection with Sydney strain 1 and a newly identified mouse-adapted strain (Sydney strain 2000) in C57BL\/6 and BALB\/c mice","volume":"72","author":"Thompson","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/(SICI)1097-0142(20000115)88:2<274::AID-CNCR5>3.0.CO;2-9","article-title":"Individual and joint contribution of family history and Helicobacter pylori infection to the risk of gastric carcinoma","volume":"88","author":"Brenner","year":"2000","journal-title":"Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.autrev.2014.01.048","article-title":"Diagnosis and classification of autoimmune gastritis","volume":"13","author":"Toh","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/sj.bjc.6605380","article-title":"Family history and the risk of gastric cancer","volume":"102","author":"Yaghoobi","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_42","first-page":"126","article-title":"Helicobacter pylori infection and family history of gastric cancer decrease expression of FHIT tumor suppressor gene in gastric mucosa of dyspeptic patients","volume":"14","author":"Peczek","year":"2009","journal-title":"Helicobacter"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.ijmm.2011.03.002","article-title":"Helicobacter pylori genotypes and types of gastritis in first-degree relatives of gastric cancer patients","volume":"301","author":"Siavoshi","year":"2011","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Queiroz, D.M., Silva, C.I., Goncalves, M.H., Braga-Neto, M.B., Fialho, A.B., Fialho, A.M., Rocha, G.A., Rocha, A.M., Batista, S.A., and Guerrant, R.L. (2012). Higher frequency of cagA EPIYA-C phosphorylation sites in H. pylori strains from first-degree relatives of gastric cancer patients. BMC Gastroenterol., 12.","DOI":"10.1186\/1471-230X-12-107"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00428-013-1458-5","article-title":"First-degree relatives of early-onset gastric cancer patients show a high risk for gastric cancer: Phenotype and genotype profile","volume":"463","author":"Carneiro","year":"2013","journal-title":"Virchows Arch."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/apt.13097","article-title":"Autoimmune gastritis in autoimmune thyroid disease","volume":"41","author":"Venerito","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1158\/1055-9965.EPI-12-1343","article-title":"Gastric parietal cell antibodies, Helicobacter pylori infection, and chronic atrophic gastritis: Evidence from a large population-based study in Germany","volume":"22","author":"Zhang","year":"2013","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.meegid.2015.07.026","article-title":"Analysis of the intactness of Helicobacter pylori cag pathogenicity island in Iranian strains by a new PCR-based strategy and its relationship with virulence genotypes and EPIYA motifs","volume":"35","author":"Yadegar","year":"2015","journal-title":"Infect. Genet. Evol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/09674845.2017.1278887","article-title":"Association of heterogenicity of Helicobacter pylori cag pathogenicity island with peptic ulcer diseases and gastric cancer","volume":"74","author":"Khatoon","year":"2017","journal-title":"Br. J. Biomed. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1046\/j.1365-2958.1999.01382.x","article-title":"Recombination and clonal groupings within Helicobacter pylori from different geographical regions","volume":"32","author":"Achtman","year":"1999","journal-title":"Mol. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1136\/gut.40.3.297","article-title":"Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection","volume":"40","author":"Parsonnet","year":"1997","journal-title":"Gut"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/(SICI)1097-0215(19981005)78:2<135::AID-IJC1>3.0.CO;2-#","article-title":"cagA-positive Helicobacter pylori and risk for developing gastric carcinoma in Brazil","volume":"78","author":"Queiroz","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/(SICI)1097-0215(19981029)78:3<298::AID-IJC6>3.0.CO;2-Q","article-title":"Infection with CagA+ Helicobacter pylori strains as a possible predictor of risk in the development of gastric adenocarcinoma in Mexico","volume":"78","author":"Torres","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/1097-0215(20000801)87:3<322::AID-IJC3>3.0.CO;2-M","article-title":"The Helicobacter pylori vacA s1, m1 genotype and cagA is associated with gastric carcinoma in Germany","volume":"87","author":"Miehlke","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.micpath.2018.06.023","article-title":"CagA and vacA allelic combination of Helicobacter pylori in gastroduodenal disorders","volume":"122","author":"Sheikh","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1128\/JCM.06293-11","article-title":"The geographic origin of Helicobacter pylori influences the association of the homB gene with gastric cancer","volume":"50","author":"Kang","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5302","DOI":"10.1128\/JCM.42.11.5302-5308.2004","article-title":"The cag pathogenicity island of Helicobacter pylori is disrupted in the majority of patient isolates from different human populations","volume":"42","author":"Kauser","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5033","DOI":"10.1073\/pnas.1018444108","article-title":"Helicobacter pylori genome evolution during human infection","volume":"108","author":"Kennemann","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000151297","article-title":"Gastric precancerous lesions and Helicobacter pylori infection in relatives of gastric cancer patients from Northeastern Brazil","volume":"78","author":"Motta","year":"2008","journal-title":"Digestion"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1097\/MEG.0b013e3283398d37","article-title":"Helicobacter pylori infection and gastric histology in first-degree relatives of gastric cancer patients: A meta-analysis","volume":"22","author":"Rokkas","year":"2010","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Liao, J., Wen, S., Cao, L., Zhou, Y., and Feng, Z. (2015). Effect of eradication of Helicobacter pylori on expression levels of FHIT, IL-8 and P73 in gastric mucosa of first-degree relatives of gastric cancer patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124576"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/MCG.0b013e3181574d39","article-title":"Higher gastric mucin secretion and lower gastric acid output in first-degree relatives of gastric cancer patients","volume":"42","author":"Vilkin","year":"2008","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1016\/j.cgh.2015.05.040","article-title":"Cancer risk after pernicious anemia in the US elderly population","volume":"13","author":"Murphy","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_64","first-page":"67","article-title":"The incidence of neoplasia in patients with autoimmune metaplastic atrophic gastritis: A renewed call for surveillance","volume":"32","author":"Mahmud","year":"2019","journal-title":"Ann. Gastroenterol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.3748\/wjg.v11.i34.5351","article-title":"Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis","volume":"11","author":"Annibale","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1111\/j.1365-2036.2012.05101.x","article-title":"Autoimmune gastritis: Histology phenotype and OLGA staging","volume":"35","author":"Rugge","year":"2012","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/j.1523-5378.2003.00187.x","article-title":"Helicobacter pylori infection and gastric autoimmune diseases: Is there a link?","volume":"8","author":"Presotto","year":"2003","journal-title":"Helicobacter"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2147\/CEG.S109123","article-title":"Autoimmune atrophic gastritis: Current perspectives","volume":"10","author":"Minalyan","year":"2017","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Parsons, B.N., Ijaz, U.Z., D\u2019Amore, R., Burkitt, M.D., Eccles, R., Lenzi, L., Duckworth, C.A., Moore, A.R., Tiszlavicz, L., and Varro, A. (2017). Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use. PLoS Pathog., 13.","DOI":"10.1101\/144907"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.3389\/fmicb.2017.02508","article-title":"The human gastric microbiome is predicated upon infection with Helicobacter pylori","volume":"8","author":"Klymiuk","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1469-0691.2000.00028.x","article-title":"Impact of treatment of Helicobacter pylori on the normal gastrointestinal microflora","volume":"6","author":"Adamsson","year":"2000","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1080\/00365540701299608","article-title":"Macrolide resistance in the normal microbiota after Helicobacter pylori treatment","volume":"39","author":"Jakobsson","year":"2007","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_73","first-page":"112","article-title":"Prevalence of Helicobacter pylori infection and its genetic heterogeneity in autoimmune atrophic chronic gastritis patients","volume":"18","author":"Zanussi","year":"2013","journal-title":"Helicobacter"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1128\/JB.188.1.249-254.2006","article-title":"Genomic changes during chronic Helicobacter pylori infection","volume":"188","author":"Kraft","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/S0966-842X(00)01791-1","article-title":"Intraspecies variation in bacterial genomes: The need for a species genome concept","volume":"8","author":"Lan","year":"2000","journal-title":"Trends Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.molmed.2004.06.001","article-title":"Gastric autoimmunity: The role of Helicobacter pylori and molecular mimicry","volume":"10","author":"Appelmelk","year":"2004","journal-title":"Trends Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1084\/jem.20030530","article-title":"Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity","volume":"198","author":"Amedei","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Roujeinikova, A. (2014). Phospholipid binding residues of eukaryotic membrane-remodelling F-BAR domain proteins are conserved in Helicobacter pylori CagA. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-525"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.4049\/jimmunol.1601765","article-title":"Reciprocal regulation of glycolysis-driven Th17 pathogenicity and regulatory T cell stability by Cdc42","volume":"200","author":"Kalim","year":"2018","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.3748\/wjg.v23.i22.3964","article-title":"Molecular mimicry in Helicobacter pylori infections","volume":"23","author":"Chmiela","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1074\/jbc.M112.435156","article-title":"Mast cell chymase degrades the alarmins heat shock protein 70, biglycan, HMGB1, and interleukin-33 (IL-33) and limits danger-induced inflammation","volume":"289","author":"Roy","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7817360","DOI":"10.1155\/2018\/7817360","article-title":"Mast cells exert anti-inflammatory effects in an IL10-\/- model of spontaneous colitis","volume":"2018","author":"Lennon","year":"2018","journal-title":"Mediators Inflamm."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/dna.2016.3432","article-title":"Regulation of autoimmunity by the Microbiome","volume":"35","author":"Horai","year":"2016","journal-title":"DNA Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4002","DOI":"10.2174\/0929867324666170508110222","article-title":"Defensive and offensive cross-reactive antibodies elicited by pathogens: The good, the bad and the ugly","volume":"24","author":"Augustyniak","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Gressmann, H., Linz, B., Ghai, R., Pleissner, K.P., Schlapbach, R., Yamaoka, Y., Kraft, C., Suerbaum, S., Meyer, T.F., and Achtman, M. (2005). Gain and loss of multiple genes during the evolution of Helicobacter pylori. PLoS Genet., 1.","DOI":"10.1371\/journal.pgen.0010043"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9999","DOI":"10.1073\/pnas.0603784103","article-title":"The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: Evolution during disease progression","volume":"103","author":"Oh","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.meegid.2011.12.002","article-title":"Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori","volume":"12","author":"Suzuki","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1440-1746.2011.06652.x","article-title":"CagA genotype and metronidazole resistant strain of Helicobacter pylori in functional dyspepsia in Thailand","volume":"26","author":"Vilaichone","year":"2011","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.bjm.2017.11.003","article-title":"Primary antibiotic resistance and its relationship with cagA and vacA genes in Helicobacter pylori isolates from Algerian patients","volume":"49","author":"Bachir","year":"2018","journal-title":"Braz. J. Microbiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1099\/jmm.0.000163","article-title":"Resistance to clarithromycin and genotypes in Helicobacter pylori strains isolated in Sicily","volume":"64","author":"Fasciana","year":"2015","journal-title":"J. Med. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"971","DOI":"10.3748\/wjg.v24.i9.971","article-title":"Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?","volume":"24","author":"Brennan","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00005-009-0007-z","article-title":"Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy","volume":"57","author":"Sugimoto","year":"2009","journal-title":"Arch. Immunol. Ther. Exp. (Warsz.)"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1046\/j.1365-2036.2001.00949.x","article-title":"High prevalence of mixed infections by Helicobacter pylori in Hong Kong: Metronidazole sensitivity and overall genotype","volume":"15","author":"Wong","year":"2001","journal-title":"Aliment. Pharmacol Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.meegid.2015.10.028","article-title":"Multiple and mixed Helicobacter pylori infections: Comparison of two epidemiological situations in Tunisia and France","volume":"37","author":"Fendri","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1099\/jmm.0.011684-0","article-title":"Helicobacter pylori oipA, vacA and dupA genetic diversity in individual hosts","volume":"59","author":"Matteo","year":"2010","journal-title":"J. Med. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.2217\/fmb-2016-0149","article-title":"Direct detection of Helicobacter pylori in biopsy specimens using a high-throughput multiple genetic detection system","volume":"11","author":"Zhang","year":"2016","journal-title":"Future Microbiol."},{"key":"ref_97","unstructured":"Isenberg, H.D. (2004). Clinical Microbiology Procedure Handbook, ASM Press, American Society Press for Microbiology. [2nd ed.]."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1097\/00000478-199600001-00004","article-title":"Recognizing atrophy: Another step toward a classification of gastritis","volume":"20","author":"Genta","year":"1996","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s10096-010-0881-7","article-title":"The cag PAI is intact and functional but HP0521 varies significantly in Helicobacter pylori isolates from Malaysia and Singapore","volume":"29","author":"Schmidt","year":"2010","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1128\/JCM.42.6.2821-2824.2004","article-title":"Multiplex PCR assay for rapid detection and genotyping of Helicobacter pylori directly from biopsy specimens","volume":"42","author":"Chattopadhyay","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/apt.12383","article-title":"Adherence to the Sydney System guidelines increases the detection of Helicobacter gastritis and intestinal metaplasia in 400738 sets of gastric biopsies","volume":"38","author":"Lash","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2016-312288","article-title":"European helicobacter and microbiota study group and consensus panel. Management of Helicobacter pylori infection-the Maastricht V\/Florence Consensus Report","volume":"66","author":"Malfertheiner","year":"2017","journal-title":"Gut"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.canlet.2017.11.009","article-title":"Gastric microbiota: An emerging player in Helicobacter pylori-induced gastric malignancies","volume":"414","author":"Espinoza","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.gpb.2017.06.002","article-title":"Human gut microbiota and gastrointestinal cancer","volume":"16","author":"Meng","year":"2018","journal-title":"Genom. Proteom. Bioinform."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/8\/2\/65\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:53:25Z","timestamp":1760187205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/8\/2\/65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,18]]},"references-count":104,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["pathogens8020065"],"URL":"https:\/\/doi.org\/10.3390\/pathogens8020065","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2019,5,18]]}}}