Differential Helicobacter pylori Plasticity in the Gastric Niche of Subjects at Increased Gastric Cancer Risk

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:1.23–31.96 in FDR; OR = 7.50; 95% CI:1.67–33.72 in GC) and a lower frequency of mixed infections (OR = 0.16; 95% CI:0.03–0.81 in FDR; OR = 0.10; 95% CI:0.02–0.48 in GC). FDR presented also an increased neutrophil infiltration (OR = 7.19; 95% CI:1.16–44.65). Both FDR and GC carried a higher proportion of CagPAI+vacAs1i1mx+homB+ profiles (OR = 2.71; 95% CI: 1.66–4.41 and OR = 3.43; 95% CI: 2.16–5.44, 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.

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Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v18i4.1417 ◽

2019 ◽

Cited By ~ 1

Author(s):

Wongwarut Boonyanugomol ◽

Kamolchanok Rukseree ◽

Worrarat Kongkasame ◽

Prasit Palittapongarnpim ◽

Seung-Chul Baik ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Progression ◽

Chemokine Receptor ◽

Gene Polymorphisms ◽

Inflammatory Responses ◽

Increased Risk ◽

Cxc Chemokine ◽

H Pylori

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.

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Helicobacter Pylori Induce Gastric Upset

Journal of Medical Research and Surgery ◽

10.52916/jmrs214055 ◽

2021 ◽

pp. 1-1

Author(s):

Hazim Abdul Rahman Alhit

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Serum Antibody ◽

Endoscopic Biopsy ◽

Helicobacter Pylori Infection ◽

Gastric Epithelium ◽

Gastric Diseases ◽

Heterogeneous Distribution ◽

Cytotoxin Associated Gene A ◽

H Pylori

Editorial: Helicobacter pylori is a micro-aerophilic, helical-form gramnegative aggressive bacteria. Accordingly, the idiom “Helico” intimates its helical appearance, “bacter” symbolizes bacteria, while “pylori” denotes stomach due to the first and common site of this bacteria living. Further, Marshall B. and Warren R. observed and described it in 1982. Then, the followed investigators studied this bacterium in detail with its consequences and complexities [1]. Gastric upset (Indigestion), dyspepsia: means impaired gastric digestion. Accordingly, the patient complains of upper abdominal pain, heartburn, belching, nausea, even feeling earlier gastric fullness than expected while eating. Furthermore, there are many causes of indigestion like gastroesophageal reflux disease, ulcer disease, gastritis, and even gastric cancer. Hence, unexplained recent onset dyspepsia in older people may need additional examinations. Moreover, one of the common causes is Helicobacter pylori infection, which needs laboratory and endoscopic examination [2]. Argument Many theories investigated the etiology and pathogenesis of Helicobacter pylori infection, concerning chronic or acute gastritis. Hence, gastric upset is the main presentation of both types of gastritis. Evidences The genotype is valuable in determining the dominant Helicobacter pylori strains as the isolates were different genetically plus heterogeneous distribution. Accordingly, the vac and cag markers operate a significant function in defining clinical consequences. These virulence agents are present in a subset of Helicobacter pylori strains isolates like cagA, iceA, vacA, and ureC. Moreover, the cagA causes cytotoxins induction by the gastric epithelial cell as Interleukin 8 [3]. The molecular intercommunication researches exhibit that the act of acarus calamus in hindering biofilm formation in Helicobacter pylori is due to the inhibitory impact of phytobio-active component, β-sitosterol, on the quorum sensing molecules-ToxB, PhnB, DnaA, plus Sip. Consequently, this opinion may suggest the molecular mechanism of Helicobacter pylori in producing the acidrelated complaints and gives a clue to a new therapy [4]. Helicobacter pylori infection causes lncRNA risk impression linked to H. pylori in gastric cancer patients and can prognosticate the prediction of these patients [5]. There was a close relationship between raised serum IgE levels in Helicobacter pylori infected patients [6]. Counterargument The laboratory investigations of Helicobacter pylori infection depend on several factors like the fluctuations of serum antibody titers in a time series, the antigene detection in stool tests, the false-positive results of lab tests, or the manner of endoscopic biopsy collection. Furthermore, other factors like the variations in Cytotoxin-Associated Gene A (CagA) in East Asian patients. Moreover, the gastric nodularity or atrophy, the patient’s age, the severity of the gastric mucosal infection are causes of variations in Helicobacter pylori detection at the time of the investigation [7]. Refutation The significant markers of H. pylori, the presence of the vacuolating cytotoxin (vacA), the cytotoxin-associated gene A (cagA), which induced by the direct communication with gastric epithelium factor antigen (iceA gene), and the presence of urease C gene (ureC). Consequently, all these factors play the principal factors in deciding the gastric consequences of Helicobacter infections. Conclusion Helicobacter pylori induce gastric upset by several mechanisms to form numerous Gastric diseases.

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Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Cells ◽

10.3390/cells9041055 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1055 ◽

Cited By ~ 11

Author(s):

Jacek Baj ◽

Izabela Korona-Głowniak ◽

Alicja Forma ◽

Amr Maani ◽

Elżbieta Sitarz ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Epithelial Mesenchymal Transition ◽

Treatment Strategies ◽

Gastric Ulcers ◽

Heparin Binding ◽

Human Pathogens ◽

Mesenchymal Transition ◽

Cytotoxin Associated Gene A ◽

H Pylori

Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world’s population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial–mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial–mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.

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Will Treatment of Helicobacter Pylori Infection in Childhood Alter the Risk of Developing Gastric Cancer?

Canadian Journal of Gastroenterology ◽

10.1155/2005/732369 ◽

2005 ◽

Vol 19 (7) ◽

pp. 409-411 ◽

Cited By ~ 41

Author(s):

Billy Bourke

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Precancerous Lesions ◽

Positive Family History ◽

Population Based ◽

Screening Programs ◽

History Of ◽

Different Populations ◽

H Pylori ◽

Developed Nations

Helicobacter pylori has been classified as a group 1 carcinogen for gastric cancer. It is estimated that there is between a two- and sixfold increase in the risk of developing gastric cancer among infected patients. Among different populations, the risk of H pylori-infected individuals developing gastric cancer varies greatly. However, on a worldwide scale, gastric cancer is the second most common cause of cancer-related death. Therefore, H pylori eradication could help prevent up to three to four million gastric cancer deaths per year. H pylori is usually acquired in childhood. Because infected children have not harboured the organism for long enough to have developed precancerous lesions, childhood is theoretically an attractive time for H pylori eradication and, thus, could help prevent gastric cancer later in life. However, as H pylori prevalence and the incidence of gastric cancer are falling rapidly in developed nations, widespread population screening programs aimed at the eradication of H pylori in these countries would be enormously expensive. Therefore, except in groups with a high risk for development of gastric cancer (eg, Japanese or those with a strong positive family history of gastric cancer), a population-based test-and-treat policy is not justified.

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Helicobacter pylori Infection and Gastric Cancer Risk: Evaluation of 15 H. pylori Proteins Determined by Novel Multiplex Serology

Cancer Research ◽

10.1158/0008-5472.can-09-0596 ◽

2009 ◽

Vol 69 (15) ◽

pp. 6164-6170 ◽

Cited By ~ 58

Author(s):

Lei Gao ◽

Angelika Michel ◽

Melanie N. Weck ◽

Volker Arndt ◽

Michael Pawlita ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Risk ◽

Risk Evaluation ◽

Helicobacter Pylori Infection ◽

Gastric Cancer Risk ◽

H Pylori ◽

Multiplex Serology

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Phylogeographic Origin of Helicobacter pylori Determines Host-Adaptive Responses upon Coculture with Gastric Epithelial Cells

Infection and Immunity ◽

10.1128/iai.01182-12 ◽

2013 ◽

Vol 81 (7) ◽

pp. 2468-2477 ◽

Cited By ~ 16

Author(s):

Alexander Sheh ◽

Rupesh Chaturvedi ◽

D. Scott Merrell ◽

Pelayo Correa ◽

Keith T. Wilson ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Helicobacter Pylori ◽

Epithelial Cells ◽

Gastric Disease ◽

Gastric Epithelial Cells ◽

Gastric Cancer Risk ◽

Content Type ◽

H Pylori ◽

Induced Apoptosis

ABSTRACTWhileHelicobacter pyloriinfects over 50% of the world's population, the mechanisms involved in the development of gastric disease are not fully understood. Bacterial, host, and environmental factors play a role in disease outcome. To investigate the role of bacterial factors inH. pyloripathogenesis, global gene expression of sixH. pyloriisolates was analyzed during coculture with gastric epithelial cells. Clustering analysis of six Colombian clinical isolates from a region with low gastric cancer risk and a region with high gastric cancer risk segregated strains based on their phylogeographic origin. One hundred forty-six genes had increased expression in European strains, while 350 genes had increased expression in African strains. Differential expression was observed in genes associated with motility, pathogenicity, and other adaptations to the host environment. European strains had greater expression of the virulence factorscagA,vacA, andbabBand were associated with increased gastric histologic lesions in patients. In AGS cells, European strains promoted significantly higher interleukin-8 (IL-8) expression than did African strains. African strains significantly induced apoptosis, whereas only one European strain significantly induced apoptosis. Our data suggest that gene expression profiles of clinical isolates can discriminate strains by phylogeographic origin and that these profiles are associated with changes in expression of the proinflammatory and protumorigenic cytokine IL-8 and levels of apoptosis in host epithelial cells. These findings support the hypothesis that bacterial factors determined by the phylogeographic origin ofH. pyloristrains may promote increased gastric disease.

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Eradication of Helicobacter pylori and Gastric Cancer: A Controversial Relationship

Frontiers in Microbiology ◽

10.3389/fmicb.2021.630852 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mariagrazia Piscione ◽

Mariangela Mazzone ◽

Maria Carmela Di Marcantonio ◽

Raffaella Muraro ◽

Gabriella Mincione

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Atrophic Gastritis ◽

Precancerous Lesions ◽

Eradication Therapy ◽

Developed Countries ◽

Gastric Carcinogenesis ◽

Gastric Disease ◽

Type I ◽

H Pylori

Worldwide, gastric cancer (GC) represents the fifth cancer for incidence, and the third as cause of death in developed countries. Indeed, it resulted in more than 780,000 deaths in 2018. Helicobacter pylori appears to be responsible for the majority of these cancers. On the basis of recent studies, and either alone or combined with additional etiological factors, H. pylori is considered a “type I carcinogen.” Over recent decades, new insights have been obtained into the strategies that have been adopted by H. pylori to survive the acidic conditions of the gastric environment, and to result in persistent infection, and dysregulation of host functions. The multistep processes involved in the development of GC are initiated by transition of the mucosa into chronic non-atrophic gastritis, which is primarily triggered by infection with H. pylori. This gastritis then progresses into atrophic gastritis and intestinal metaplasia, and then to dysplasia, and following Correa’s cascade, to adenocarcinoma. The use of antibiotics for eradication of H. pylori can reduce the incidence of precancerous lesions only in the early stages of gastric carcinogenesis. Here, we first survey the etiology and risk factors of GC, and then we analyze the mechanisms underlying tumorigenesis induced by H. pylori, focusing attention on virulence factor CagA, inflammation, oxidative stress, and ErbB2 receptor tyrosine kinase. Moreover, we investigate the relationships between H. pylori eradication therapy and other diseases, considering not only cardia (upper stomach) cancers and Barrett’s esophagus, but also asthma and allergies, through discussion of the “hygiene hypothesis. ” This hypothesis suggests that improved hygiene and antibiotic use in early life reduces microbial exposure, such that the immune response does not become primed, and individuals are not protected against atopic disorders, asthma, and autoimmune diseases. Finally, we overview recent advances to uncover the complex interplay between H. pylori and the gut microbiota during gastric carcinogenesis, as characterized by reduced bacterial diversity and increased microbial dysbiosis. Indeed, it is of particular importance to identify the bacterial taxa of the stomach that might predict the outcome of gastric disease through the stages of Correa’s cascade, to improve prevention and therapy of gastric carcinoma.

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Gastric Microbiota in Helicobacter pylori-Negative and -Positive Gastritis Among High Incidence of Gastric Cancer Area

Cancers ◽

10.3390/cancers11040504 ◽

2019 ◽

Vol 11 (4) ◽

pp. 504 ◽

Cited By ~ 14

Author(s):

Boldbaatar Gantuya ◽

Hashem B. El-Serag ◽

Takashi Matsumoto ◽

Nadim J. Ajami ◽

Khasag Oyuntsetseg ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Bacterial Species ◽

Rrna Gene ◽

Linear Discriminant ◽

Haemophilus Parainfluenzae ◽

Increased Risk ◽

Comparison Groups ◽

H Pylori ◽

Gastric Microbiota

Helicobacter pylori (H. pylori) related chronic gastritis is a well-known major etiological factor for gastric cancer development. However, H. pylori-negative gastritis (HpN) is not well described. We aimed to examine gastric mucosal microbiota in HpN compared to H. pylori-positive gastritis (HpP) and H. pylori-negative non-gastritis group (control). Here, we studied 11 subjects with HpN, 40 with HpP and 24 controls. We performed endoscopy with six gastric biopsies. Comparison groups were defined based on strict histological criteria for the disease and H. pylori diagnosis. We used 16S rRNA gene amplicon sequencing to profile the gastric microbiota according to comparison groups. These results demonstrate that the HpP group had significantly lower bacterial richness by the operational taxonomic unit (OTU) counts, and Shannon and Simpson indices as compared to HpN or controls. The linear discriminant analysis effect size analysis showed the enrichment of Firmicutes, Fusobacteria, Bacteroidetes and Actinobacteria at phylum level in the HpN group. In the age-adjusted multivariate analysis, Streptococcus sp. and Haemophilus parainfluenzae were at a significantly increased risk for HpN (odds ratio 18.9 and 12.3, respectively) based on abundance. Treponema sp. was uniquely found in HpN based on occurrence. In this paper, we conclude that Streptococcus sp., Haemophilus parainfluenzae and Treponema sp. are candidate pathogenic bacterial species for HpN. These results if confirmed may have important clinical implications.

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Precancerous Gastric Lesions with Helicobacter pylori vacA+/babA2+/oipA+ Genotype Increase the Risk of Gastric Cancer

BioMed Research International ◽

10.1155/2020/7243029 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Theeraya Simawaranon Bartpho ◽

Wareeporn Wattanawongdon ◽

Taweesak Tongtawee ◽

Chatchanok Paoin ◽

Kokiet Kangwantas ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Clinical Outcomes ◽

Chronic Gastritis ◽

Virulence Genes ◽

Gastric Lesions ◽

Precancerous Gastric Lesions ◽

Increased Risk ◽

H Pylori ◽

Gastric Cancer Patients

Objective. The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods. Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori infection and virulence genes (cagA, vacA, iceA2, babA2, and oipA) were determined using real-time PCR. The association between H. pylori genotypes and clinical outcomes were evaluated using multivariate regression model analysis. The overall survival of gastric cancer patients was compared between genotype combinations. Results. H. pylori was positive in 166 patients with chronic gastritis, precancerous gastric lesions, and gastric cancer. The genes vacA, babA2, and oipA were most prevalent in chronic gastritis (73%), precancerous gastric lesions (62%), and gastric cancer (91%), respectively. The vacA, babA2, and oipA genes were associated with increased risk of gastric cancer (OR = 1.23; 95% CI = 1.13–3.32; P=0.033, OR = 2.64; 95% CI = 1.44–4.82, P=0.024, and OR = 2.79; 95% CI = 1.58–5.41; P=0.031, respectively). Interestingly, H. pylori vacA+/babA2+/oipA+ genotype infection was associated with increased risk of gastric cancer (OR = 3.85, 95% CI = 1.67–5.77, P=0.014). Conclusion. In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.

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Polymorphism in Toll-Like Receptors and Helicobacter Pylori Motility in Autoimmune Atrophic Gastritis and Gastric Cancer

Cancers ◽

10.3390/cancers11050648 ◽

2019 ◽

Vol 11 (5) ◽

pp. 648 ◽

Cited By ~ 3

Author(s):

Valli De Re ◽

Ombretta Repetto ◽

Mariangela De Zorzi ◽

Mariateresa Casarotto ◽

Massimo Tedeschi ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Atrophic Gastritis ◽

Toll Like Receptors ◽

Innate And Adaptive Immunity ◽

Healthy Donors ◽

Increased Risk ◽

Host Cell Interactions ◽

H Pylori ◽

Autoimmune Atrophic Gastritis

Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adaptive immunity responses. This study therefore aimed to characterize TLR polymorphisms, and features of bacterial flagellin A in samples from patients with AAG (n = 67), GC (n = 114) and healthy donors (HD; n = 97). TLR5 rs5744174 C/C genotype was associated with GC, lower IgG anti H. pylori response and a higher H. pylori flagellin A abundance and motility. In a subset of patients with AAG, H. pylori strains showed a reduction of the flagellin A abundance and a moderate motility compared with strains from GC patients, a prerequisite for active colonization of the deeper layers of the mucosa, host immune response and inflammation. TLR9 rs5743836 T allele showed an association with serum gastrin G17. In conclusion, our study suggests that alterations of flaA protein, moderate motility in H. pylori and two polymorphisms in TLR5 and TLR9 may favor the onset of AAG and GC, at least in a subset of patients. These findings corroborate the function of pathogen–host cell interactions and responses, likely influencing the pathogenetic process.

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