Evaluation of Lineage Changes in the Gastric Mucosa Following Infection With Helicobacter pylori and Specified Intestinal Flora in INS-GAS Mice

Gastric adenocarcinoma develops in metaplastic mucosa associated with Helicobacter pylori infection in the stomach. We have sought to evaluate the precise lineage changes in the stomachs of insulin-gastrin (INS-GAS) mice infected with H. pylori and/or intestinal flora (Altered Schaedler’s Flora; ASF). Stomachs from groups infected with H. pylori contained progressive spasmolytic polypeptide-expressing metaplasia (SPEM) compared with germ-free and mice infected with ASF alone. The overall phenotype of the H. pylori-infected mice was dominated by Ulex europaeus lectin (UEAI)-positive foveolar hyperplasia that was distinct from GSII/CD44v9-positive SPEM. However, in the mice with H. pylori co-infected with ASF, we identified a subpopulation of UEAI-positive foveolar cells that co-expressed intestinal mucin 4 (MUC4). These regions of foveolar cells were variably positive for CD44v9 as well as TFF3. Interestingly, an intravascular lesion identified in a dual H. pylori/ASF-infected mouse expressed both UEAI and Muc4. Finally, we identified an increase in the number of tuft cells within the mucosa of H. pylori-infected groups. Our findings suggest that H. pylori infection promotes foveolar hyperplasia as well as metaplasia, while co-infection may promote progressive foveolar and metaplastic lesions as well as dysplasia. Grading of gastric lesions in mice as preneoplastic requires multiple immunostaining markers to assign lineage derivation and behavior.

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The Degree of Helicobacter pylori Infection Affects the State of Macrophage Polarization through Crosstalk between ROS and HIF-1α

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5281795 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Ying Lu ◽

Jianfang Rong ◽

Yongkang Lai ◽

Li Tao ◽

Xiaogang Yuan ◽

...

Keyword(s):

Helicobacter Pylori ◽

Macrophage Polarization ◽

Polarization State ◽

Hypoxia Inducible Factor ◽

Mtor Pathway ◽

Raw 264.7 Cells ◽

Gastric Lesions ◽

M1 Phenotype ◽

H Pylori ◽

M2 Phenotype

Background and Objective. Helicobacter pylori (H. pylori) is involved in macrophage polarization, but the specific mechanism is not well understood. Therefore, this study is aimed at investigating the effects of the degree of H. pylori infection on the macrophage polarization state and the crosstalk between reactive oxygen species (ROS) and hypoxia-inducible factor 1 α (HIF-1α) in this process. Methods. The expression of CD86, CD206, and HIF-1α in the gastric mucosa was evaluated through immunohistochemistry. RAW 264.7 cells were cocultured with H. pylori at various multiplicities of infection (MOIs), and iNOS, CD86, Arg-1, CD206, and HIF-1α expression was detected by Western blot, PCR, and ELISA analyses. ROS expression was detected with the fluorescent probe DCFH-DA. Macrophages were also treated with the ROS inhibitor NAC or HIF-1α inhibitor YC-1. Results. Immunohistochemical staining revealed that the macrophage polarization state was associated with the progression of gastric lesions and state of H. pylori infection. The MOI of H. pylori affected macrophage polarization, and H. pylori enhanced the expression of ROS and HIF-1α in macrophages. A low MOI of H. pylori promoted both the M1 and M2 phenotypes, while a high MOI suppressed the M2 phenotype. Furthermore, ROS inhibition attenuated HIF-1α expression and switched macrophage polarization from M1 to M2. However, HIF-1α inhibition suppressed ROS expression and inhibited both the M1 phenotype and the M2 phenotype. Inhibition of ROS or HIF-1α also suppressed the activation of the Akt/mTOR pathway, which was implicated in H. pylori-induced macrophage polarization. Conclusions. Macrophage polarization is associated with the progression of gastric lesions and state of H. pylori infection. The MOI of H. pylori influences the macrophage polarization state. Crosstalk between ROS and HIF-1α regulates H. pylori-induced macrophage polarization via the Akt/mTOR pathway.

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Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease.

Journal of Experimental Medicine ◽

10.1084/jem.179.5.1653 ◽

1994 ◽

Vol 179 (5) ◽

pp. 1653-1658 ◽

Cited By ~ 383

Author(s):

J L Telford ◽

P Ghiara ◽

M Dell'Orco ◽

M Comanducci ◽

D Burroni ◽

...

Keyword(s):

Helicobacter Pylori ◽

Peptic Ulcer ◽

Gastric Mucosa ◽

Chronic Infection ◽

Gastric Disease ◽

Human Gastric Mucosa ◽

Gastric Lesions ◽

Gram Negative ◽

H Pylori ◽

Cytotoxin Gene

The gram negative, microaerophilic bacterium Helicobacter pylori colonizes the human gastric mucosa and establishes a chronic infection that is tightly associated with atrophic gastritis, peptic ulcer, and gastric carcinoma. Cloning of the H. pylori cytotoxin gene shows that the protein is synthesized as a 140-kD precursor that is processed to a 94-kD fully active toxin. Oral administration to mice of the purified 94-kD protein caused ulceration and gastric lesions that bear some similarities to the pathology observed in humans. The cloning of the cytotoxin gene and the development of a mouse model of human gastric disease will provide the basis for the understanding of H. pylori pathogenesis and the development of therapeutics and vaccines.

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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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Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial

Gut ◽

10.1136/gutjnl-2016-311685 ◽

2017 ◽

Vol 67 (7) ◽

pp. 1239-1246 ◽

Cited By ~ 49

Author(s):

Robertino M Mera ◽

Luis E Bravo ◽

M Constanza Camargo ◽

Juan C Bravo ◽

Alberto G Delgado ◽

...

Keyword(s):

Helicobacter Pylori ◽

Linear Models ◽

Precancerous Lesions ◽

Gastric Lesions ◽

Logistic Regression Models ◽

Risk Of Progression ◽

H Pylori ◽

Cumulative Time

ObjectiveTo evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions.Design795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of H. pylori exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1–6). The score difference between baseline and 16 years was modelled by generalised linear models.ResultsIndividuals who were continuously infected with H. pylori for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with H. pylori. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001).ConclusionsLong-term exposure to H. pylori infection was associated with progression of precancerous lesions. Individuals infected with H. pylori with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.

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Real-time diagnostic yield of white light endoscopy, chromoendoscopy and magnifying endoscopy with narrow band imaging in the undiagnosed gastric lesions after Helicobacter pylori eradication

10.21203/rs.2.11211/v1 ◽

2019 ◽

Author(s):

Tomomitsu Tahara ◽

Noriyuki Horiguchi ◽

Tsuyoshi Terada ◽

Dai Yoshida ◽

Masaaki Okubo ◽

...

Keyword(s):

Helicobacter Pylori ◽

Real Time ◽

Narrow Band ◽

Narrow Band Imaging ◽

Diagnostic Yield ◽

Consensus Meeting ◽

Magnifying Endoscopy ◽

Gastric Lesions ◽

White Light Endoscopy ◽

H Pylori

Abstract Background: Early-stage gastric cancer (EGC) after Helicobacter pylori (H. pylori) often confuse endoscopic diagnosis. We prospectively evaluated the real-time diagnostic yield of combining white light endoscopy (WLE), chromoendoscopy (CE), and magnifying endoscopy with narrow band imaging (ME-NBI) for undiagnosed gastric lesions after H. pylori eradication. Methods: Using a retrospective data set, we conducted a consensus meeting to learn ME-NBI features of EGC after H. pylori eradication associated with diagnostic difficulty. Then, we prospectively evaluated the real-time diagnostic yield of WL, followed by CE, and ME-NBI in the diagnosis of 166 newly identified gastric lesions from 219 patients after H. pylori eradication. Results: A consensus meeting characterized ME-NBI feature of EGC with diagnostic difficulty, as having irregular vessel patterns in only tiny area of the lesion. Among 166 undiagnosed gastric lesions in the prospective study, 22 neoplastic lesions (18 adenocarcinomas and 4 adenomas) were identified. In these lesions, diagnosed case was dramatically increased when combined with ME-NBI (98%) compared to WLE alone (54%) and CE with WLE (63%) (WLE+CE+ME-NBI vs. others, all P<0.0001). In the diagnosed cases, the diagnostic accuracy was also improved when combined with ME-NBI (99.4%) compared to WLE alone (92.2%: P=0.004) and CE with WLE (95.1%: P=0.03). Conclusions: WLE combined with ME-NBI can improve the diagnostic yield of EGC in patients after H. pylori eradication. For precise diagnosis of EGC by ME-NBI, it is essential to detect irregular vessels.

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Association of Helicobacter pylori vacA polymorphisms with the risk of gastric precancerous lesions in a Moroccan population

The Journal of Infection in Developing Countries ◽

10.3855/jidc.14435 ◽

2021 ◽

Vol 15 (08) ◽

pp. 1124-1132

Author(s):

Mohamed Reda Jouimyi ◽

Ghizlane Bounder ◽

Imane Essaidi ◽

Hasna Boura ◽

Wafaa Badre ◽

...

Keyword(s):

Helicobacter Pylori ◽

High Risk ◽

Atrophic Gastritis ◽

Intestinal Metaplasia ◽

Chronic Gastritis ◽

Precancerous Lesions ◽

Gastric Lesions ◽

D Region ◽

Reliable Marker ◽

H Pylori

Introduction: Helicobacter pylori infection is the major risk factor of atrophic gastritis and intestinal metaplasia. The vacA gene is one of the most virulence factors of H. pylori and genetic diversity in its s, m, i, and d regions is associated with gastric lesions severity. This study aimed to investigate the association of vacA s, m, i, and d regions with the risk of atrophic gastritis and intestinal metaplasia in a Casablanca population. Methodology: A total of 210 patients suffering from gastric lesions (chronic gastritis, atrophic gastritis, and intestinal metaplasia) were enrolled. The type of lesion was diagnosed by histological examination. Detection of H. pylori infection and genotyping of vacA regions were carried out by PCR. Results: The prevalence of H. pylori was 95%. The most common vacA genotypes were s2 (51.5%), m2 (77%), i2 (60.5%), and d2 (58.5%). VacA s1, m1, and i1 genotypes were associated with a high risk of intestinal metaplasia, while the vacA d1 genotype increases the risk of atrophic gastritis and intestinal metaplasia. The most common vacA combination was s2/m2/i2/d2 (52%), and it was more detected in chronic gastritis. The moderate virulent vacA combination (s1/m2/i1/d1) increases the risk of atrophic gastritis, while the most virulent vacA combination (s1/m1/i1/d1) increases the risk of intestinal metaplasia. Conclusions: Genotyping of vacA d region might be a reliable marker for the identification of vacA virulent strains that represent a high risk of developing precancerous lesions (atrophic gastritis and intestinal metaplasia).

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Infection with Helicobacter Pylori Presenting the vacA s2m2 haplotype is Strongly Associated with Protection Against Gastric Cancer

10.21203/rs.3.rs-250522/v1 ◽

2021 ◽

Author(s):

Alix Guevara-Tique ◽

Fabian Castro Valencia ◽

John Jairo Suaréz Olaya ◽

Roberto Carlos Torres ◽

Giovanna Parra ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Virulence Genes ◽

Mortality Rates ◽

South American ◽

Gastric Lesions ◽

Preneoplastic Lesions ◽

Main Risk Factor ◽

South American Region ◽

H Pylori

Abstract Background: Infection with Helicobacter pylori is recognized as the main risk factor for gastric cancer (GC); the clinical outcome of this infection is variable and partially depends on the virulence of the infective strain. This study characterizes H. pylori virulence genes in patients with diverse gastric lesions, from preneoplasia to GC, from a South American region with high GC mortality rates.Methods: We studied the virulence profiles of H. pylori strains to colonize the antrum of 318 patients with non-atrophic gastritis (NAG), 58 patients with preneoplastic lesions (PN), and 90 with GC from Ibagué, Colombia. The presence of 16S rDNA, the cagA and cagE genes, and the vacA s1, s2, m1, and m2 alleles were determined by PCR.Results: H. pylori infection was detected in 44% of all patients, 41.2% in NAG, 43.1% in PN and 54.4% of GC patients (p= 0.0813). cagA and cagE genes were significantly more frequent in and GC than in NAG (p= <.0001). The vacA s1m1 haplotype was significantly more frequent in PN (68%) and GC (65.3%) than in NAG (37.4%). The frequency of vacA s2m2 haplotype decreased significantly from NAG (42.7%) to PN (12%) and this to GC (4.1%). A total of 23 different genotypes were identified, with cagA+/cagE+/vacA s1m1 (84/205) as the more frequent in PN and GC and cagA-/cagE-/vacA s2m2 in NAG (49/205).Conclusions: In the population studied, vacA s2m2 was identified as a significant marker for protection against PN and GC, and genotype cagA+/cagE+/vacA s1m1 as a marker for increased GC risk. We also found that patients with PN and GC had a higher frequency of cagA+/cagE+/vacA s1m1 H. pylori strains known to be aggressive.

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Helicobacteriosis: changes of the mucosa in disorder of motor functions (motorics) in the gastroesophagal and duodenogastral zones of the stomach

Doklady of the National Academy of Sciences of Belarus ◽

10.29235/1561-8323-2021-65-1-96-102 ◽

2021 ◽

Vol 65 (1) ◽

pp. 96-102

Author(s):

O. O. Yanovich ◽

L. P. Titov ◽

M. V. Doroshko ◽

I. G. Sergeeva ◽

S. A. Guzov

Keyword(s):

Duodenal Ulcer ◽

Helicobacter Pylori ◽

Gastric Mucosa ◽

Reflux Esophagitis ◽

Morphological Changes ◽

Duodenogastric Reflux ◽

Study Group ◽

Foveolar Hyperplasia ◽

Increased Risk ◽

H Pylori

The morphological changes in the gastric mucosa in the presence of duodenogastric reflux and refluxesophagitis and their connection with the presence of Helicobacter pylori (HP) infection are studied. The endoscopic and histological examination of the stomach antral part was performed in 1251 patients with different gastroduodenal pathologies. HP was diagnosed by histological and real-time PCR methods. Among patients with different gastroduodenal pathologies the frequency of H. pylori infection was 77.9 %. Duodenogastric reflux was detected in 23.9 % of patients. In the presence of duodenogastric reflux, we have found a decrease in the risk of duodenal ulcer by a factor of 2.5, thus duodenogastric reflux may protect against the development of duodenal ulcer. In patients with duodenogastric reflux in the presence of H. pylori infection, significant differences from the group uninfected of Helicobacter pylori were found in the metaplasia frequency. A significant increase in the frequency of foveolar hyperplasia among patients with duodenogastric reflux was revealed. The prevalence of reflux-esophagitis in the study group was 8.3 %. No increased risk in reflux-esophagitis was observed either in the HP-positive or HP-negative cases. According to our finding, duodenogastric reflux was characterized by foveolar hyperplasia and metaplasia. We suggest that the presence or absence of H. pylori does not affect reflux-esophagitis.

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The rod-to-coccoid body transformation in cultures of Helicobacter pylori

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100160686 ◽

1990 ◽

Vol 48 (3) ◽

pp. 626-627

Author(s):

A. R. Crooker ◽

W. G. Kraft ◽

T. L. Beard ◽

M. C. Myers

Keyword(s):

Helicobacter Pylori ◽

Growth Cycle ◽

Negative Bacterium ◽

Body Formation ◽

Coccoid Form ◽

Spiral Form ◽

Prolonged Culture ◽

H Pylori ◽

Upper Gastrointestinal

Helicobacter pylori is a microaerophilic, gram-negative bacterium found in the upper gastrointestinal tract of humans. There is strong evidence that H. pylori is important in the etiology of gastritis; the bacterium may also be a major predisposing cause of peptic ulceration. On the gastric mucosa, the organism exists as a spiral form with one to seven sheathed flagella at one (usually) or both poles. Short spirals were seen in the first successful culture of the organism in 1983. In 1984, Marshall and Warren reported a coccoid form in older cultures. Since that time, other workers have observed rod and coccal forms in vitro; coccoid forms predominate in cultures 3-7 days old. We sought to examine the growth cycle of H. pylori in prolonged culture and the mode of coccoid body formation.

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