scholarly journals Eradication of Helicobacter pylori and Gastric Cancer: A Controversial Relationship

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.

scholarly journals Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals

2020 ◽  
Vol 21 (17) ◽  
pp. 6451 ◽  
Author(s):  
James W. T. Toh ◽  
Robert B. Wilson
Keyword(s):  
Gastric Cancer ◽  
Ascorbic Acid ◽  
Helicobacter Pylori ◽  
Vitamin C ◽  
Atrophic Gastritis ◽  
Chronic Atrophic Gastritis ◽  
Gastric Carcinogenesis ◽  
Antioxidant Systems ◽  
H Pylori

Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.

scholarly journals Significance of Helicobacter pylori Eradication on Atrophic Gastritis and Intestinal Metaplasia

2020 ◽  
Vol 20 (2) ◽  
pp. 107-116
Author(s):  
Kichul Yoon ◽  
Nayoung Kim
Keyword(s):  
Helicobacter Pylori ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Precancerous Lesions ◽  
Eradication Therapy ◽  
Diffuse Type ◽  
Helicobacter Pylori Eradication ◽  
Predicting Factors ◽  
Point Of No Return ◽  
H Pylori

There has been an accumulation of data regarding the chemopreventive effects of <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication. However, it remains unclear how <i>H. pylori</i> infection causes gastric cancer (GC) and how <i>H. pylori</i> eradication can prevent GC. Atrophic gastritis (AG) and intestinal metaplasia (IM) are known as precancerous lesions which mainly lead to intestinal-type GC but to some extent, can also lead to diffuse-type GC. The most important mechanism of AG/IM is <i>H. pylori</i>-induced chronic gastritis. Thus, the reversibility of AG and IM by <i>H. pylori</i> eradication therapy is very important in the prevention of GC. There have been many studies providing data supporting the improvement of AG by the eradication of <i>H. pylori</i> to some extent. In contrast, IM has been regarded as “the point of no return.” However, more recent studies have implied the improvement of IM after eradication, suggesting the importance of early eradication therapy in reversible histological status. In this review, we focused on the reversibility of AG and IM by <i>H. pylori</i> eradication and tried to investigate the predicting factors for the improvement of AG and IM including age, sex, smoking, and diet, as well as <i>H. pylori</i> infection.

scholarly journals Helicobacter pylori-Induced Signaling Pathways Contribute to Intestinal Metaplasia and Gastric Carcinogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Soichiro Sue ◽  
Wataru Shibata ◽  
Shin Maeda
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Gastric Carcinogenesis ◽  
Dependent Manner ◽  
Intracellular Signaling Pathways ◽  
H Pylori

Helicobacter pylori(H. pylori) induces chronic gastric inflammation, atrophic gastritis, intestinal metaplasia, and cancer. Although the risk of gastric cancer increases exponentially with the extent of atrophic gastritis, the precise mechanisms of gastric carcinogenesis have not been fully elucidated.H. pyloriinduces genetic and epigenetic changes in gastric epithelial cells through activating intracellular signaling pathways in a cagPAI-dependent manner.H. pylorieventually induces gastric cancer with chromosomal instability (CIN) or microsatellite instability (MSI), which are classified as two major subtypes of gastric cancer. Elucidation of the precise mechanisms of gastric carcinogenesis will also be important for cancer therapy.

scholarly journals Changes in Gastric Microbial Composition before and after Helicobacter pylori Eradication Therapy

2020 ◽  
Vol 20 (3) ◽  
pp. 177-186
Author(s):  
Chan Hyuk Park
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Microbial Diversity ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Diversity Index ◽  
Eradication Therapy ◽  
Cancer Development ◽  
Microbial Composition ◽  
H Pylori

Owing to advancements in next-generation sequencing and non-culture-based microbial research techniques, we have recognized that many bacterial taxa other than <i>Helicobacter pylori (H. pylori)</i> are present in the human stomach. Gastric microbial composition depends on gastric diseases, including gastritis, atrophic gastritis, intestinal metaplasia, and gastric cancer. Although <i>H. pylori</i> is a major factor associated with gastric cancer development, other bacterial taxa may affect gastric carcinogenesis. Because the risk of gastric cancer development can be reduced through <i>H. pylori</i> eradication, many investigators have studied the changes in the microbial composition in the stomach after <i>H. pylori</i> eradication. The gastric microbiome in patients with <i>H. pylori</i> infection typically shows abundance of <i>H. pylori</i> and a low microbial diversity index. If we treat <i>H. pylori</i>-infected patients with antibiotics, microbial diversity increases, and the relative abundance also increases in many bacterial taxa. Several studies suggested that the microbial composition in patients with <i>H. pylori</i> infection could be restored by <i>H. pylori</i> eradication therapy; however, there have been inconsistent findings of the abundant bacterial taxa after <i>H. pylori</i> eradication in patients with atrophic gastritis and intestinal metaplasia. More studies are required to reach a definitive conclusion on restoration of the microbial composition after <i>H. pylori</i> eradication according to the severity of gastric inflammation.

scholarly journals Helicobacter pylori-Induced Inflammation: Possible Factors Modulating the Risk of Gastric Cancer

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1099
Author(s):  
Sushil Kumar ◽  
Girijesh Kumar Patel ◽  
Uday C. Ghoshal
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Tissue Injury ◽  
Precancerous Lesions ◽  
Gastric Carcinogenesis ◽  
Future Research ◽  
Intestinal Helminths ◽  
H Pylori

Chronic inflammation and long-term tissue injury are related to many malignancies, including gastric cancer (GC). Helicobacter pylori (H. pylori), classified as a class I carcinogen, induces chronic superficial gastritis followed by gastric carcinogenesis. Despite a high prevalence of H. pylori infection, only about 1–3% of people infected with this bacterium develop GC worldwide. Furthermore, the development of chronic gastritis in some, but not all, H. pylori-infected subjects remains unexplained. These conflicting findings indicate that clinical outcomes of aggressive inflammation (atrophic gastritis) to gastric carcinogenesis are influenced by several other factors (in addition to H. pylori infection), such as gut microbiota, co-existence of intestinal helminths, dietary habits, and host genetic factors. This review has five goals: (1) to assess our current understanding of the process of H. pylori-triggered inflammation and gastric precursor lesions; (2) to present a hypothesis on risk modulation by the gut microbiota and infestation with intestinal helminths; (3) to identify the dietary behavior of the people at risk of GC; (4) to check the inflammation-related genetic polymorphisms and role of exosomes together with other factors as initiators of precancerous lesions and gastric carcinoma; and (5) finally, to conclude and suggest a new direction for future research.

scholarly journals Endoscopic Mucosal Phenotypes in the Helicobacter Pylori Infection

2019 ◽  
Vol 16 (1) ◽  
pp. 21-32
Author(s):  
Geanina Tudor ◽  
Roxana Călin ◽  
Nuta Petrut ◽  
Ioniţă Radu Florentina ◽  
Jinga Mariana ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Carcinogenesis ◽  
Helicobacter Pylori Infection ◽  
Type I ◽  
Digestive Endoscopy ◽  
Bacterial Colonisation ◽  
Diagnosis Method ◽  
Upper Digestive Endoscopy ◽  
H Pylori

AbstractIntroduction. H. pylori infection occurs secondary to the bacterial colonisation of the stomach and the first portion of the small intestine. Patients infected with H. pylori can develop gastritis, peptic ulcer, gastric cancer, and MALT lymphoma. H. pylori infection is defined as a type I carcinogen by the WHO, and its role in gastric carcinogenesis is sustained by many studies.Objectives. The objective of this study was the description and correlation of the endoscopic aspect of the gastric mucosa in the Helicobacter pylori infection and the incidence in a selected patient group.Material and method. The study was conducted in the “Dr Carol Davila” Central Military University Emergency Hospital, Section of Gastroenterology, Department of digestive endoscopy, during a period of 12 months (2012--2013) on 1690 consecutive examinations on patients with ages between 18 and 92 years, with a retrospective cohort analytic study. As diagnosis method of the individuals infected with H. pylori, upper digestive endoscopy was used.During the intervention, biopsieswere taken and rapid urease tests were performed.Results. Regarding the variation of these endoscopic aspects within the examined population, we determined the fact that we encounter in the highest percentage gastritis with all its forms according to the Sidney classification (described below) which represents 59.3%, followed by endoscopic determination with a normal aspect in 18.8% of cases, then follows ulcer with a percentage of 10.33%, followed by duodenitis with 8.67%, and finally the most severe conditions, gastric cancer and lymphoma, reaching only 2.70% and 0.18%, respectively, of the general population examined endoscopically.

Prevalence of Helicobacter pylori infection among blood donors in Saxony-Anhalt, Germany – a region at intermediate risk for gastric cancer

2017 ◽  
Vol 55 (07) ◽  
pp. 653-656 ◽  
Author(s):  
Caspar Franck ◽  
Armin Hoffmann ◽  
Alexander Link ◽  
Christian Schulz ◽  
Kerstin Wuttig ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Blood Donors ◽  
Eradication Therapy ◽  
Surrogate Marker ◽  
University Hospital ◽  
Study Cohort ◽  
Emergency Ward ◽  
Age Related ◽  
H Pylori

Abstract Background In the federal state of Saxony-Anhalt, gastric cancer (GC) incidence ranks among the highest in Germany. Helicobacter pylori prevalence is a surrogate marker for GC risk in a given population. In 2010 we reported an H. pylori seroprevalence of 44.4 % in patients at the emergency ward of the University Hospital of Magdeburg, the capital of Saxony-Anhalt. Our aim is to update these findings in a cohort of healthy blood donors from the same region. Materials and methods The sera of 516 consecutive blood donors (40.1 ± 14.1 years; 286 males and 230 females) were tested for antibodies against H. pylori and CagA. Data on demographics and previous H. pylori eradication therapy were obtained by means of a structured questionnaire. Blood donors with positive serology for H. pylori or CagA and/or history of eradication therapy were classified as H. pylori-positive. Results Overall, 28.9 % of the study cohort were H. pylori-positive. The prevalence was higher in older generations (9 % in 18 – 20 years up to 47 % in 61 – 70 years). In 44.4 % of H. pylori IgG-positive donors, CagA serology was also positive. This proportion was not age-dependent. Study participants with siblings were by trend more often H. pylori-positive (p = 0.066). Conclusion Compared to our previous study in patients at the emergency ward, we found by trend lower age-related H. pylori prevalence rates. In our cohort of healthy blood donors, we confirmed a lower H. pylori prevalence in younger generations.

scholarly journals Induction and prevention of gastric cancer with combined Helicobacter pylori and capsaicin administration and DFMO treatment, respectively

2020 ◽  
Author(s):  
Faisal Aziz ◽  
Mingxia Xin ◽  
Yunfeng Gao ◽  
Josh Monts ◽  
Kjersten Monson ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Mouse Models ◽  
Chronic Gastritis ◽  
Molecular Mechanisms ◽  
Gastric Carcinogenesis ◽  
Lifestyle Changes ◽  
Host Susceptibility ◽  
Anti Inflammatory ◽  
H Pylori

Abstract Background: Gastric cancer risk evolves over time due to environmental, dietary, and lifestyle changes including Helicobacter pylori (H. pylori) infection and consumption of hot peppers (i.e. capsaicin). H. pylori infection promotes gastric mucosal injury in the early phase of capsaicin exposure. In addition, capsaicin consumption is reported to suppress immune function and increase host susceptibility to microbial infection. This relationship suggests a need to investigate the mechanism of how both H. pylori infection and capsaicin contribute to gastric inflammation and lead to gastric cancer. No previous experimental animal models have been developed to study this dual association. Here we developed a series of mouse models that progress from chronic gastritis to gastric cancer. C57-Balb/c mice were infected with the H. pylori (SS1) strain and then fed capsaicin (0.05% or 0.2g/kg/day) or not. Consequently, we investigated the association between H. pylori infection and capsaicin consumption during the initiation of gastric inflammation and the later development of gastric cancer. Tumor size and phenotype were analyzed to determine the molecular mechanism driving the shift from gastritis to stomach cancer. Gastric carcinogenesis was also prevented in these models using the ornithine decarboxylase inhibitor DFMO (2-difluoromethylornithine). Results: This study provides evidence showing that a combination of H. pylori infection and capsaicin consumption leads to gastric carcinogenesis. The transition from chronic gastritis to gastric cancer is mediated through interleukin-6 (IL-6) stimulation with an incidence rate of 50%. However, this progression can be prevented by treating with anti-inflammatory agents. In particular, we used DFMO to prevent gastric tumorigenesis by reducing inflammation and promoting recovery of disease-free stasis. The anti-inflammatory role of DFMO highlights the injurious effect of inflammation in gastric cancer development and the need to reduce gastric inflammation for cancer prevention. Conclusions: Overall, these mouse models provide reliable systems for analyzing the molecular mechanisms and synergistic effects of H. pylori and capsaicin on human cancer etiology. Accordingly, preventive measures like reduced capsaicin consumption, H. pylori clearance, and DFMO treatment can lessen gastric cancer incidence. Lastly, anti-inflammatory agents like DFMO can play important roles in prevention of inflammation-associated gastric cancer.

Evaluation of the Epidemiologic Efficacy of Eradicating Helicobacter pylori on Development of Gastric Cancer

2019 ◽  
Vol 41 (1) ◽  
pp. 97-108 ◽  
Author(s):  
Fujiao Duan ◽  
Chunhua Song ◽  
Jintao Zhang ◽  
Peng Wang ◽  
Hua Ye ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Population Attributable Risk ◽  
Eradication Therapy ◽  
Attributable Risk ◽  
Chinese Patients ◽  
Controlled Trials ◽  
Mixed Effect ◽  
H Pylori ◽  
Development Of Gastric Cancer

Abstract Eradication of Helicobacter pylori colonization has been reported to affect the progression of gastric cancer. A comprehensive literature search was performed from 1997 to 2017 using electronic databases. All randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCT) evaluated the effect of H. pylori eradication on development of gastric cancer. Four RCTs and 9 non-RCTs were included (n = 40,740 participants; 321,269 person-years). Overall, H. pylori eradication therapy was associated with a significantly reduced risk of gastric cancer (incidence rate ratio (IRR) = 0.52, 95% confidence interval (CI): 0.41, 0.65). Results of mixed-effect Poisson regression meta-analysis were similar to those of traditional meta-analyses. In stratified analyses, the IRRs were 0.59 (95% CI: 0.41, 0.86) in RCTs and 0.48 (95% CI: 0.36, 0.64) in non-RCTs. The IRRs were 0.45 (95% CI: 0.34, 0.61) in patients and 0.63 (95% CI: 0.44, 0.90) in the general population. Moreover, the relative risk reduction was approximately 77% on the development of noncardiac gastric cancer with H. pylori eradication therapy in China. Attributable risk percentage and population attributable risk percentage for Chinese patients were 77.08% and 75.33%, respectively, and for Japanese patients were 57.80% and 45.99%, respectively. H. pylori eradication therapy reduces the risk of noncardiac gastric cancer development. The findings indicate the importance of early intervention with H. pylori eradication therapy from the perspective of epidemiology.

scholarly journals The role of the gastric bacterial microbiome in gastric cancer: Helicobacter pylori and beyond

2019 ◽  
Vol 12 ◽  
pp. 175628481989406 ◽  
Author(s):  
Christian Schulz ◽  
Kerstin Schütte ◽  
Julia Mayerle ◽  
Peter Malfertheiner
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Bacterial Pathogen ◽  
Gastric Carcinogenesis ◽  
Nucleotide Sequencing ◽  
Wide Field ◽  
Current State ◽  
Organ Systems ◽  
Bacterial Microbiome ◽  
H Pylori

A link between chronic inflammation and carcinogenesis has been depicted in many organ systems. Helicobacter pylori is the most prevalent bacterial pathogen, induces chronic gastritis and is associated with more than 90% of cases of gastric cancer (GC). However, the introduction of nucleotide sequencing techniques and the development of biocomputional tools have surpassed traditional culturing techniques and opened a wide field for studying the mucosal and luminal composition of the bacterial gastric microbiota beyond H. pylori. In studies applying animal models, a potential role in gastric carcinogenesis for additional bacteria besides H. pylori has been demonstrated. At different steps of gastric carcinogenesis, changes in bacterial communities occur. Whether these microbial changes are a driver of malignant disease or a consequence of the histologic progression along the precancerous cascade, is not clear at present. It is hypothesized that atrophy, as a consequence of chronic gastric inflammation, alters the gastric niche for commensals that might further urge the development of H. pylori-induced GC. Here, we review the current state of knowledge on gastric bacteria other than H. pylori and on their synergism with H. pylori in gastric carcinogenesis.

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