Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori

Bilgilier, Ceren; Stadlmann, Alexander; Makristathis, Athanasios; Thannesberger, Jakob; Kastner, Marie-Theres; Knoflach, P; Steiner, P; Schöniger–Hekele, Maximilian; Högenauer, Christoph; Blesl, Andreas; Datz, Christian; Huber-Schönauer, Ursula; Schöfl, R; Wewalka, F; Püspök, Andreas; Mitrovits, N; Leiner, Judith; Tilg, Herbert; Effenberger, Maria; Moser, Mike; Siebert, F; Hinterberger, I.; Wurzer, H; Stupnicki, T; Watzinger, Norbert; Gombotz, G; Hubmann, Rainer; Klimpel, Sven; Biowski-Frotz, Susanne; Schrutka-Kölbl, C; Graziadei, Ivo; Ludwiczek, Othmar; Kundi, Michael; Hirschl, Alexander M.; Steininger, Christoph

doi:10.1016/j.cmi.2017.06.025

Cited by 24 publications

(16 citation statements)

References 35 publications

(41 reference statements)

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“…The total prevalence of H . pylori was much lower than previously reported(23–50%) [ 4 , 18 , 19 ]. The reason is not completely clear but might be partially influenced by a selection bias since the study institution is a tertiary referral center specialized for the treatment of patients with liver diseases (who mostly have a high chance to be treated with antibiotics during the course of their disease).…”

Section: Discussioncontrasting

confidence: 71%

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Prevalence of Helicobacter pylori and its CagA subtypes in gastric cancer and duodenal ulcer at an Austrian tertiary referral center over 25 years

et al. 2018

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Background and aimsThe prevalence of Helicobacter pylori (H. pylori) tends to be lower in Western countries such as central Europe compared with Asia. The virulence of H. pylori is influenced by its subtype composition, most importantly by the presence or absence of different types of cytotoxin-associated gene A(CagA). This study aimed to assess the prevalence of H. pylori and its respective CagA phenotype in a large retrospective cohort of patients with gastric cancer or duodenal ulcer at a Western tertiary referral institution.MethodsH. pylori positive gastric biopsy samples from patients diagnosed with the afore mentioned diseases within the past 25 years were re-evaluated by histology for H. pylori and status of gastritis. Confirmed H. pylori positive cases were processed for immunohistochemistry (IHC) for H. pylori,CagA, and EastAsiantype CagA.ResultsThe prevalence of H. pylori positive gastric biopsy samples decreased from 20.7% to 2.3% within the study period. Among the gastric cancer patients, the H. pylori positive rate was 16.6%, and didn’t show significant changes over time (p = 0.38). Contrary, the H. pylori positive rate of duodenal ulcer decreased significantlyfrom 40% to 5% (p = 0.01). Within H. pylori positive groups ofboth diseases, CagA was highly detected at IHC (86% and 78%, respectively). Except for a few patients originating from East Asian countries, all CagA detected in this study were of Western type.ConclusionIn this first Western investigation on the chronological prevalence of H. pylori and its most relevant subtypes, Western type of CagA was highly detected in two important index diseases of the pathogen. This raises further questions about the virulence of this subtype.

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Section: Discussioncontrasting

confidence: 71%

“…In Austria, for example, the prevalence rate of H . pylori infection was found to be 23% in a recent study [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Helicobacter pylori and its CagA subtypes in gastric cancer and duodenal ulcer at an Austrian tertiary referral center over 25 years

et al. 2018

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“…and CagA status but not according to their diagnosis. Samples were selected randomly from a cohort of more than 2000 human gastric biopsies (Bilgilier et al, 2017 ). A written informed consent was obtained from all participants.…”

Section: Methodsmentioning

confidence: 99%

“…Histomorphological evaluation of one of the two gastric biopsy samples for the presence of Helicobacter-like organisms (HLO) was done with the use of hematoxylin and eosin staining and a modified Giemsa staining followed by microscopic evaluation according to standard procedures (Fallone et al, 1997 ) and as described in detail in Bilgilier et al ( 2017 ). For the detection of H.p.-specific DNA, the second fresh gastric biopsy sample from each patient was homogenized in 1 ml 0.9% NaCl solution (Sigma Aldrich) using Lysing Matrix D tubes with ceramic beads (MP Biomedicals) in an FastPrep®-24 Instrument (MP Biomedicals) at 4.5m/s for 20 s once.…”

Section: Methodsmentioning

confidence: 99%

The Human Gastric Microbiome Is Predicated upon Infection with Helicobacter pylori

et al. 2017

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The human gastric lumen is one of the most hostile environments of the human body suspected to be sterile until the discovery of Helicobacter pylori (H.p.). State of the art next generation sequencing technologies multiply the knowledge on H.p. functional genomics as well as on the colonization of supposed sterile human environments like the gastric habitat. Here we studied in a prospective, multicenter, clinical trial the 16S rRNA gene amplicon based bacterial microbiome in a total of 30 homogenized and frozen gastric biopsy samples from eight geographic locations. The evaluation of the samples for H.p. infection status was done by histopathology and a specific PCR assay. CagA status was determined by a CagA-specific PCR assay. Patients were grouped accordingly as H.p.-negative, H.p.-positive but CagA-negative and H.p.-positive and CagA-positive (n = 10, respectively). Here we show that H.p. infection of the gastric habitat dominates the gastric microbiota in most patients and is associated with a significant decrease of the microbial alpha diversity from H.p. negative to H.p. positive with CagA as a considerable factor. The genera Actinomyces, Granulicatella, Veillonella, Fusobacterium, Neisseria, Helicobacter, Streptococcus, and Prevotella are significantly different between the H.p.-positive and H.p.-negative sample groups. Differences in microbiota found between CagA-positive and CagA-negative patients were not statistically significant and need to be re-evaluated in larger sample cohorts. In conclusion, H.p. infection dominates the gastric microbiome in a multicentre cohort of patients with varying diagnoses.

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“…Multiple studies have demonstrated that socioeconomic status and ethnic origin of the population are strongly associated with prevalence of H. pylori infection[3-5]. In Central and Northern Europe, H. pylori prevalence, excluding non-European immigrants, was found to be around 24% to 32%[6-10]. Studies conducted in Switzerland revealed a H. pylori prevalence of 12%-20% in patients born in Swit-zerland and a prevalence of 27% in immigrants[5,11].…”

Section: Helicobacter Pylori Prevalence Epidemiology and Antibiotic mentioning

confidence: 99%

Review of current diagnostic methods and advances inHelicobacter pyloridiagnostics in the era of next generation sequencing

Pohl

Keller

Bordier

et al. 2019

WJG

116

113

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Helicobacter pylori ( H. pylori ) infection is highly prevalent in the human population and may lead to severe gastrointestinal pathology including gastric and duodenal ulcers, mucosa associated tissue lymphoma and gastric adenocarcinoma. In recent years, an alarming increase in antimicrobial resistance and subsequently failing empiric H. pylori eradication therapies have been noted worldwide, also in many European countries. Therefore, rapid and accurate determination of H. pylori ’s antibiotic susceptibility prior to the administration of eradication regimens becomes ever more important. Traditionally, detection of H.pylori and its antimicrobial resistance is done by culture and phenotypic drug susceptibility testing that are cumbersome with a long turn-around-time. Recent advances in diagnostics provide new tools, like real-time polymerase chain reaction (PCR) and line probe assays, to diagnose H. pylori infection and antimicrobial resistance to certain antibiotics, directly from clinical specimens. Moreover, high-throughput whole genome sequencing technologies allow the rapid analysis of the pathogen’s genome, thereby allowing identification of resistance mutations and associated antibiotic resistance. In the first part of this review, we will give an overview on currently available diagnostic methods for detection of H. pylori and its drug resistance and their implementation in H. pylori management. The second part of the review focusses on the use of next generation sequencing technology in H. pylori research. To this end, we conducted a literature search for original research articles in English using the terms “ Helicobacter ”, “transcriptomic”, “transcriptome”, “next generation sequencing” and “whole genome sequencing”. This review is aimed to bridge the gap between current diagnostic practice (histology, rapid urease test, H. pylori culture, PCR and line probe assays) and new sequencing technologies and their potential implementation in diagnostic laboratory settings in order to complement the currently recommended H. pylori management guidelines and subsequently improve public health.

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Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori

Cited by 24 publications

References 35 publications

Prevalence of Helicobacter pylori and its CagA subtypes in gastric cancer and duodenal ulcer at an Austrian tertiary referral center over 25 years

Prevalence of Helicobacter pylori and its CagA subtypes in gastric cancer and duodenal ulcer at an Austrian tertiary referral center over 25 years

The Human Gastric Microbiome Is Predicated upon Infection with Helicobacter pylori

Review of current diagnostic methods and advances inHelicobacter pyloridiagnostics in the era of next generation sequencing

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