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Helicobacter pylori Infection and Gastritis

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (15 May 2019) | Viewed by 102346

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Dr. Sun-Young Lee

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Guest Editor

Department of Internal Medicine, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Republic of Korea
Interests: gastric cancer; gastritis; Helicobacter pylori infection; gastrointestinal endoscopy

Special Issue Information

Dear Colleagues,

Helicobacter pylori (H. pylori) leads to gastritis in the human stomach, with significant changes in terms of microbial composition. Nonetheless, most infected subjects are asymptomatic in an endemic area of H. pylori infection. Therefore, it is important to discriminate H. pylori-infected subjects using serology and endoscopy findings, regardless of symptoms. Nevertheless, there are few data on various stages of H. pylori-related gastritis. Furthermore, there is no comparison study on the different microbial environment between the “chronic gastritis with a risk of intestinal-type gastric cancer in hypochlorhydric environments” and the “active gastritis with a risk of diffuse-type gastric cancer in hyperacidic conditions”. The severity of gastritis, based on endoscopy and histopathological findings, should be discussed in the near future, with gastric secretory ability reflected using serum pepsinogen assay. This will help in understanding the differences between H. pylori-induced microbial dysbiosis in active gastritis and microbial diversity in chronic gastritis.

Prof. Dr. Sun-Young Lee
Guest Editor

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Keywords

Gastritis
Helicobacter pylori
Endoscopy
Microbiota
Gastric cancer

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Published Papers (9 papers)

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Research

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13 pages, 585 KiB

Open AccessArticle

Antibiotic Resistance and Genotypes of Helicobacter pylori Strains in Patients with Gastroduodenal Disease in Southeast Poland

by Izabela Korona-Glowniak, Halina Cichoz-Lach, Radoslaw Siwiec, Sylwia Andrzejczuk, Andrzej Glowniak, Przemyslaw Matras and Anna Malm

J. Clin. Med. 2019, 8(7), 1071; https://doi.org/10.3390/jcm8071071 - 21 Jul 2019

Cited by 23 | Viewed by 4809

Abstract

The aim of this study was to investigate genetic diversity of Helicobacter pylori virulence markers to predict clinical outcome as well as to determine an antibiotic susceptibility of H. pylori strains in Poland. Gastric biopsies from 132 patients with gastrointestinal disorders were tested for presence of H. pylori with the use of rapid urease test, microbial culture, and polymerase chain reaction (PCR) detection. The genetic diversity of 62 H. pylori positive samples was evaluated by detection of cagA and PCR-typing of vacA and iceA virulence-associated genes. Most common H. pylori genotypes were cagA(+)vacAs1m2 (27.4%) and cagA(−)vacAs2m2 (24.2%). In logistic regression analysis, we recognized the subsequent significant associations: gastritis with ureC, i.e., H. pylori infection (p = 0.006), BMI index (p = 0.032); and negatively with iceA1 (p = 0.049) and peptic ulcer with cagA (p = 0.018). Thirty-five H. pylori strains were cultured and tested by E-test method showing that 49% of strains were resistant to at least one of the tested antibiotics. This is the first study that reports the high incidence and diversity of allelic combination of virulence genes in gastroduodenitis patients in Poland. Genotyping of H. pylori strains confirmed the involvement of cagA gene and vacAs1m1 genotype in development and severity of gastric disorder. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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16 pages, 1399 KiB

Open AccessArticle

Rapid Characterization of Virulence Determinants in Helicobacter pylori Isolated from Non-Atrophic Gastritis Patients by Next-Generation Sequencing

by Frank Imkamp, Francis N. Lauener, Daniel Pohl, Philippe Lehours, Filipa F. Vale, Quentin Jehanne, Reinhard Zbinden, Peter M. Keller and Karoline Wagner

J. Clin. Med. 2019, 8(7), 1030; https://doi.org/10.3390/jcm8071030 - 12 Jul 2019

Cited by 18 | Viewed by 4713

Abstract

Helicobacter pylori is a major human pathogen that causes a wide range of gastrointestinal pathology. Progression of H. pylori induced gastritis to more severe disease has been found to highly correlate with the array of virulence factors expressed by the pathogen. The objective of this study was twofold: first, to characterize the genetic diversity of H. pylori strains isolated from 41 non-atrophic gastritis patients in Switzerland, an issue that has not been investigated to date. And second, to assess the prevalence and sequence variation of H. pylori virulence factors (cagA, vacA, iceA and dupA) and genes encoding outer membrane proteins (OMPs; babA, babB, sabA, sabB, hopZ, hopQ and oipA) by whole genome sequencing (WGS) using an Illumina MiSeq platform. WGS identified high genetic diversity in the analyzed H. pylori strains. Most H. pylori isolates were assigned to hpEurope (95.0%, 39/41), and the remaining ones (5.0%, 2/41) to hpEastAsia, subpopulation hspEAsia. Analysis of virulence factors revealed that 43.9% of the strains were cagA-positive, and the vacA s1 allele was detected in 56.0% of the isolates. The presence of cagA was found to be significantly associated (P < 0.001) with the presence of vacA s1, babA2 and hopQ allele 1 as well as expression of oipA. Moreover, we found an association between the grade of gastritis and H. pylori abundance in the gastric mucosa, respectively and the presence of cagA, vacA s1 and hopQ allele 1. Among our 41 gastritis patients, we identified seven patients infected with H. pylori strains that carried a specific combination of virulence factors (i.e., cagA, vacA s1 allele and babA2 allele), recently implicated in the development of more severe gastrointestinal pathology, like peptic ulcer disease and even gastric cancer. To this end, WGS can be employed for rapid and detailed characterization of virulence determinants in H. pylori, providing valuable insights into the pathogenic capacity of the bacterium. This could ultimately lead to a higher level of personalized treatment and management of patients suffering from H. pylori associated infections. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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15 pages, 1778 KiB

Open AccessArticle

A Next-Generation Sequencing-Based Approach to Identify Genetic Determinants of Antibiotic Resistance in Cambodian Helicobacter pylori Clinical Isolates

by Vo Phuoc Tuan, Dou Narith, Evariste Tshibangu-Kabamba, Ho Dang Quy Dung, Pham Thanh Viet, Sin Sokomoth, Tran Thanh Binh, Sok Sokhem, Tran Dinh Tri, Seng Ngov, Pham Huu Tung, Ngo Phuong Minh Thuan, Tran Cong Truc, Bui Hoang Phuc, Takashi Matsumoto, Kartika Afrida Fauzia, Junko Akada, Tran Thi Huyen Trang and Yoshio Yamaoka

J. Clin. Med. 2019, 8(6), 858; https://doi.org/10.3390/jcm8060858 - 15 Jun 2019

Cited by 62 | Viewed by 7442

Abstract

We evaluated the primary resistance of Helicobacter pylori (H. pylori) to routinely used antibiotics in Cambodia, an unexplored topic in the country, and assessed next-generation sequencing’s (NGS) potential to discover genetic resistance determinants. Fifty-five H. pylori strains were successfully cultured and screened for antibiotic susceptibility using agar dilution. Genotypic analysis was performed using NGS data with a CLC genomic workbench. PlasmidSeeker was used to detect plasmids. The correlation between resistant genotypes and phenotypes was evaluated statistically. Resistances to metronidazole (MTZ), levofloxacin (LVX), clarithromycin (CLR), and amoxicillin (AMX) were 96.4%, 67.3%, 25.5%, and 9.1%, respectively. No resistance to tetracycline (TET) was observed. Multi-drug resistance affected 76.4% of strains. No plasmids were found, but genetic determinants of resistance to CLR, LVX, and AMX were 23S rRNA (A2146G and A2147G), GyrA (N87K and D91Y/N/G), and pbp1 (P473L), respectively. No determinants were genetically linked to MTZ or TET resistance. There was high concordance between resistant genotypes and phenotypes for AMX, LVX, and CLR. We observed high antibiotic resistance rates of CLR, MTZ, and LVX, emphasizing the need for periodic evaluation and alternative therapies in Cambodia. NGS showed high capability for detecting genetic resistance determinants and potential for implementation in local treatment policies. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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15 pages, 873 KiB

Open AccessArticle

Deregulation of miRNA in Helicobacter pylori-Induced Gastric MALT Lymphoma: From Mice to Human

by Alice Blosse, Michael Levy, Cyrielle Robe, Cathy Staedel, Christiane Copie-Bergman and Philippe Lehours

J. Clin. Med. 2019, 8(6), 845; https://doi.org/10.3390/jcm8060845 - 13 Jun 2019

Cited by 20 | Viewed by 3945

Abstract

Gastric MALT lymphoma (GML) is directly caused by Helicobacter pylori infection but occurs only in a small number of infected subjects. Mechanisms underlying the initiation and progression of GML remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs that are now considered as major players in inflammation and carcinogenesis, acting as oncogenes or tumor suppressors. Previous laboratory studies have shown in a GML mouse model that overexpression of a distinct set of five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) could play a critical role in the pathogenesis of GML. Our goal was to compare the miRNA expression profile obtained in the GML mouse model to that in human GML (11 cases of GML compared to 17 cases of gastritis control population). RTqPCR on the five dysregulated miRNAs in the GML mouse model and PCR array followed by RTqPCR confirmation showed that four miRNAs were up-regulated (miR-150, miR-155, miR-196a, miR-138) and two miRNAs down-regulated (miR-153, miR-7) in the stomachs of GML patients vs. gastritis control population. The analysis of their validated targets allowed us to postulate that these miRNAs (except miR-138) could act synergistically in a common signaling cascade promoting lymphomagenesis and could be involved in the pathogenesis of GML. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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36 pages, 13836 KiB

Open AccessArticle

Prediction of Chronic Atrophic Gastritis and Gastric Neoplasms by Serum Pepsinogen Assay: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

by Chang Seok Bang, Jae Jun Lee and Gwang Ho Baik

J. Clin. Med. 2019, 8(5), 657; https://doi.org/10.3390/jcm8050657 - 10 May 2019

Cited by 57 | Viewed by 5824

Abstract

Serum pepsinogen assay (sPGA), which reveals serum pepsinogen (PG) I concentration and the PG I/PG II ratio, is a non-invasive test for predicting chronic atrophic gastritis (CAG) and gastric neoplasms. Although various cut-off values have been suggested, PG I ≤70 ng/mL and a PG I/PG II ratio of ≤3 have been proposed. However, previous meta-analyses reported insufficient systematic reviews and only pooled outcomes, which cannot determine the diagnostic validity of sPGA with a cut-off value of PG I ≤70 ng/mL and/or PG I/PG II ratio ≤3. We searched the core databases (MEDLINE, Cochrane Library, and Embase) from their inception to April 2018. Fourteen and 43 studies were identified and analyzed for the diagnostic performance in CAG and gastric neoplasms, respectively. Values for sensitivity, specificity, diagnostic odds ratio, and area under the curve with a cut-off value of PG I ≤70 ng/mL and PG I/PG II ratio ≤3 to diagnose CAG were 0.59, 0.89, 12, and 0.81, respectively and for diagnosis of gastric cancer (GC) these values were 0.59, 0.73, 4, and 0.7, respectively. Methodological quality and ethnicity of enrolled studies were found to be the reason for the heterogeneity in CAG diagnosis. Considering the high specificity, non-invasiveness, and easily interpretable characteristics, sPGA has potential for screening of CAG or GC. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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14 pages, 1192 KiB

Open AccessArticle

Correlations of the Gastric and Duodenal Microbiota with Histological, Endoscopic, and Symptomatic Gastritis

by Hye Seung Han, Sun-Young Lee, Seo Young Oh, Hee Won Moon, Hyunseok Cho and Ji-Hoon Kim

J. Clin. Med. 2019, 8(3), 312; https://doi.org/10.3390/jcm8030312 - 5 Mar 2019

Cited by 25 | Viewed by 7115

Abstract

Mucosal inflammation is characterized by neutrophil and mononuclear cell infiltration. This study aimed to determine the gastric and duodenal microbiota associated with histological, endoscopic, and symptomatic gastritis. Dyspeptic adults who presented for evaluation were included. Subjects with either comorbidities or recent drug intake were excluded. Three endoscopic biopsies were obtained from the antrum, body, and duodenum. Next-generation sequencing for 16S ribosomal RNA V1–V2 hypervariable regions was performed. The correlation between the composition of microbiota and the degree of inflammatory cell infiltration, endoscopic findings, and Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) score was analyzed. In 98 included subjects, microbial communities in the antrum and body showed Bray–Curtis similarity; however, those in the duodenum showed dissimilarity. Histological and endoscopic gastritis was associated with the abundance of Helicobacter pylori and that of commensal bacteria in the stomach. The abundances of Variovorax paradoxus and Porphyromonas gingivalis were correlated with histological gastritis, but not with endoscopic or symptomatic gastritis. The total PAGI-SYM score showed a stronger correlation with the duodenal microbiota (Prevotella nanceiensis and Alloprevotella rava) than with the gastric microbiota (H. pylori, Neisseria elongate, and Corynebacterium segmentosum). Different correlations of the gastric and duodenal microbiota with histological, endoscopic, and symptomatic gastritis were observed for the first time at the species level. H. pylori-negative gastritis is not associated with endoscopic or symptomatic gastritis. Only H. pylori-induced endoscopic gastritis requires gastric cancer surveillance. Owing to the weak correlation with H. pylori, symptomatic gastritis should be assessed separately from histological and endoscopic gastritis. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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16 pages, 2428 KiB

Open AccessArticle

Probiotic Lactobacillus spp. Act Against Helicobacter pylori-induced Inflammation

by Yi-Hsing Chen, Wan-Hua Tsai, Hui-Yu Wu, Chun-Ya Chen, Wen-Ling Yeh, Ya-Hui Chen, Hui-Ying Hsu, Wei-Wei Chen, Yu-Wen Chen, Wen-Wei Chang, Tzu-Lung Lin, Hsin-Chih Lai, Yu-Hsin Lin and Chih-Ho Lai

J. Clin. Med. 2019, 8(1), 90; https://doi.org/10.3390/jcm8010090 - 14 Jan 2019

Cited by 98 | Viewed by 11813

Abstract

The bacterial species, Helicobacter pylori, is associated with several gastrointestinal diseases, and poses serious health threats owing to its resistance to antibiotics. Lactobacillus spp., on the other hand, possess probiotic activities that have beneficial effects in humans. However, the mechanisms by which Lactobacillus spp. harbor favorable functions and act against H. pylori infection remain to be explored. The aim of this study was to investigate the ability of bacterial strains, Lactobacillus rhamnosus and Lactobacillus acidophilus, termed GMNL-74 and GMNL-185, respectively, to inhibit H. pylori growth and inflammation. Our results showed that GMNL-74 and GMNL-185 possess potent antimicrobial activity against multidrug resistant (MDR)-H. pylori. In addition, an in vitro cell-based model revealed that the inhibition of H. pylori adhesion and invasion of gastric epithelial cells and interleukin-8 production were significantly decreased by treatment with both the Lactobacillus strains. In vivo studies demonstrated that colonization of H. pylori and induced inflammation in the mouse stomach were also alleviated by these Lactobacillus strains. Furthermore, the abundance of beneficial gut bacteria, including Bifidobacterium spp. and Akkermansia muciniphilia, were significantly increased in H. pylori-infected mice treated with GMNL-74 and GMNL-185. These results demonstrate that Lactobacillus spp. ameliorate H. pylori-induced inflammation and supports beneficial gut specific bacteria that act against H. pylori infection. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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14 pages, 728 KiB

Open AccessArticle

Genetic Determinants and Prediction of Antibiotic Resistance Phenotypes in Helicobacter pylori

by Francis N. Lauener, Frank Imkamp, Philippe Lehours, Alice Buissonnière, Lucie Benejat, Reinhard Zbinden, Peter M. Keller and Karoline Wagner

J. Clin. Med. 2019, 8(1), 53; https://doi.org/10.3390/jcm8010053 - 7 Jan 2019

Cited by 101 | Viewed by 7583

Abstract

Helicobacter pylori is a major human pathogen. Diagnosis of H. pylori infection and determination of its antibiotic susceptibility still mainly rely on culture and phenotypic drug susceptibility testing (DST) that is time-consuming and laborious. Whole genome sequencing (WGS) has recently emerged in medical microbiology as a diagnostic tool for reliable drug resistance prediction in bacterial pathogens. The aim of this study was to compare phenotypic DST results with the predictions based on the presence of genetic determinants identified in the H. pylori genome using WGS. Phenotypic resistance to clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was determined in 140 clinical H. pylori isolates by E-Test^®, and the occurrence of certain single nucleotide polymorphisms (SNPs) in target genes was determined by WGS. Overall, there was a high congruence of >99% between phenotypic DST results for clarithromycin, levofloxacin, and rifampicin and SNPs identified in the 23S rRNA, gyrA, and rpoB gene. However, it was not possible to infer a resistance phenotype for metronidazole based on the occurrence of distinct SNPs in frxA and rdxA. All 140 H. pylori isolates analysed in this study were susceptible to tetracycline, which was in accordance with the absence of double or triple nucleotide substitutions in the 16S rRNA gene. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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Review

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19 pages, 660 KiB

Open AccessReview

Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options

by Lucija Kuna, Jelena Jakab, Robert Smolic, Nikola Raguz-Lucic, Aleksandar Vcev and Martina Smolic

J. Clin. Med. 2019, 8(2), 179; https://doi.org/10.3390/jcm8020179 - 3 Feb 2019

Cited by 238 | Viewed by 47600

Abstract

Peptic ulcer is a chronic disease affecting up to 10% of the world’s population. The formation of peptic ulcers depends on the presence of gastric juice pH and the decrease in mucosal defenses. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major factors disrupting the mucosal resistance to injury. Conventional treatments of peptic ulcers, such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, have demonstrated adverse effects, relapses, and various drug interactions. On the other hand, medicinal plants and their chemical compounds are useful in the prevention and treatment of numerous diseases. Hence, this review presents common medicinal plants that may be used for the treatment or prevention of peptic ulcers. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection and Gastritis)

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