The Role of Helicobacter Pylori Infection in the Development of Gastric Cancer - Review of the Literature.

Helicobacter pylori (H. pylori), classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC), is linked to gastric cancer. The progression from atrophy to metaplasia, dysplasia, and carcinoma constitutes the pathway for intestinal-type gastric carcinoma development. H. pylori infection significantly increases gastric cancer risk, particularly in individuals with atrophic gastritis. Virulence factors like CagA and VacA disrupt host signaling pathways, contributing to chronic inflammation and carcinogenesis. Pro-inflammatory cytokines and dysregulated tumor suppressor genes further fuel this process. Eradicating H. pylori reduces gastric cancer incidence, especially in patients with atrophic gastritis and/or intestinal metaplasia. However, it may not prevent cancer in those with advanced pre-neoplastic lesions. Early detection and management of H. pylori infection are crucial in mitigating gastric cancer risk, offering significant benefits.

Helicobacter Pylori and Gastric Cancer: An Update in the Literature.

Of the chronic bacterial infections that affect humans, Helicobacter pylori (H. pylori) infection is one of the most common. It inhabits the stomachs of half of the adult human population. In Puerto Rico, a US territory, it has an overall prevalence of 33%, similar to the prevalence reported in the population of the US as a whole. Helicobacter pylori infection is responsible for mucosal inflammation that may lead to chronic gastritis, most peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The International Agency for Research on Cancer identified H. pylori as a definite carcinogen in 1994, the only bacterium to be given such a classification. Its oncogenic effect has been postulated to be caused by different mechanisms, including bacterial characteristics and host factors. Epidemiologic studies have shown that gastric cancer risk differs among regions. One of the top 10 causes of cancer death in Puerto Rico is gastric cancer. Although the eradication of H. pylori has well-known benefits, there are some concerns when considering mass screening and treatment of infected patients. These include the fact that such eradication could provoke an increase in antibiotic resistance rates, the disturbance of the gut microbiota, an increase in body weight, and the aggravation of existing gastroesophageal reflux symptoms. Gastric cancer is a major health concern, and we should understand the role of H. pylori eradication in its prevention. This article is geared to summarize current knowledge and controversies.

Predicting Personalized Diets Based on Microbial Characteristics between Patients with Superficial Gastritis and Atrophic Gastritis.

BACKGROUND: gastritis is a common stomach disease with a high global incidence and can potentially develop into gastric cancer. The treatment of gastritis focuses on medication or diets based on national guidelines. However, the specific diet that can alleviate gastritis remains largely unknown. METHODS: we propose a microbiota-directed dietary strategy that investigates potential food factors using microbial exogenous metabolites. Given the current lack of understanding of the repeatable characteristics of gastric microbiota, we conducted a meta-analysis to identify the features of gastric bacteria. Local samples were collected as validation cohorts. Furthermore, RevEcoR was employed to identify bacteria's exogenous metabolites, and FooDB was used to retrieve foods that can target specific bacteria. RESULTS: Bacteroides, Weissella, Actinomyces, Atopobium, Oribacterium, Peptostreptococcus, and Rothia were biomarkers between superficial gastritis (SG) and atrophic gastritis (AG) (AG_N) without H. pylori infection, whereas Bacillus, Actinomyces, Cutibacterium, Helicobacter, Novosphingobium, Pseudomonas, and Streptococcus were signatures between SG and AG (AG_P) with H. pylori infection. According to the exogenous metabolites, adenosyloobalamin, soybean, common wheat, dates, and barley were regarded as potential candidates for AG_N treatment, while gallate was regarded as a candidate for AG_P treatment. CONCLUSIONS: this study firstly profiled the gastric microbiota of AG and SG with or without H. pylori and provided a recommended diet for global AG according to exogenous metabolites.

The 'reversibility' of chronic atrophic gastritis after the eradication of Helicobacter pylori.

Gram-negative bacterium Helicobacter pylori (H. pylori) infection is lifelong and usually acquired in childhood, which is etiologically linked to gastric cancer (GC). H. pylori gastritis is defined as an infectious disease with varying severity in virtually all infected subjects. Chronic atrophic gastritis (CAG) is the precancerous condition with the decrease or the loss of gastric glands, which can further be replaced by metaplasia or fibrosis. Patients with advanced stages of CAG are at higher risk of GC and should be followed up with a high-quality endoscopy every 3 years. H. pylori infection is the most common cause and its eradication is recommended, which may contribute to the regression of CAG. However, it is controversial whether CAG is reversible after eradication therapy. In the review, we discuss recent studies which provide important insights into whether CAG is 'reversibility' and when it may progress into GC after eradicating H. pylori.

Immunological Perspective: Helicobacter pylori Infection and Gastritis.

Helicobacter pylori is a spiral-shaped gram-negative bacterium. Its infection is mainly transmitted via oral-oral and fecal-oral routes usually during early childhood. It can achieve persistent colonization by manipulating the host immune responses, which also causes mucosal damage and inflammation. H. pylori gastritis is an infectious disease and results in chronic gastritis of different severity in near all patients with infection. It may develop from acute/chronic inflammation, chronic atrophic gastritis, intestinal metaplasia, dysplasia, and intraepithelial neoplasia, eventually to gastric cancer. This review attempts to cover recent studies which provide important insights into how H. pylori causes chronic inflammation and what the characteristic is, which will immunologically explain H. pylori gastritis.

Evaluation of the Gastric Microbiome in Patients with Chronic Superficial Gastritis and Intestinal Metaplasia.

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis (CSG) and intestinal metaplasia (IM) and investigate the influence of Helicobacter pylori (H. pylori) on the gastric microbiome. Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM, and the patients were classified into the following four groups based on the state of H. pylori infection and histology: H. pylori-negative CSG (n=24), H. pylori-positive CSG (n=14), H. pylori-negative IM (n=11), and H. pylori-positive IM (n=5). The gastric microbiome was analyzed by 16S rRNA gene sequencing. Results H. pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM. In H. pylori-positive subjects, the bacterial abundance and diversity were significantly lower than in H. pylori-negative subjects. The H. pylori-negative groups had similar bacterial composition and bacterial abundance. The H. pylori-positive groups also had similar bacterial composition but different bacterial relative abundance. The relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella were richer in the I-HP group than in G-HP group, especially Neisseria (t=175.1, P<0.001). Conclusions The gastric microbial abundance and diversity are lower in H. pylori- infected patients regardless of CSG and IM. Compared to H. pylori-positive CSG group and H. pylori-positive IM, the relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella is higher in H. pylori-positive patients with IM than in H. pylori-positive patients with CSG, especially Neisseria.

Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection.

Gastric cancer (GC) is the fifth most common cancer and the fourth most common cause of cancer-related death worldwide. The intestinal type of GC progresses from acute to chronic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and carcinoma. Infection of the stomach by Helicobacter pylori, a Gram-negative bacterium that infects approximately 50% of the world's population, is the causal determinant that initiates the gastric inflammation and then disease progression. In this context, the induction of the innate immune response of gastric epithelial cells and myeloid cells by H. pylori effectors plays a critical role in the outcome of the infection. However, only 1% to 3% of infected patients develop gastric adenocarcinoma, emphasizing that other mechanisms regulate the localized non-specific response, including the gastric microbiota and genetic factors. This review summarizes studies describing the factors that induce and regulate the mucosal innate immune response during H. pylori infection.

Identifying the Profile of Helicobacter pylori-Negative Gastric Cancers: A Case-Only Analysis within the Stomach Cancer Pooling (StoP) Project.

BACKGROUND: The prevalence of Helicobacter pylori-negative gastric cancer (HpNGC) can be as low as 1%, when infection is assessed using more sensitive tests or considering the presence of gastric atrophy. HpNGC may share a high-risk profile contributing to the occurrence of cancer in the absence of infection. We estimated the proportion of HpNGC, using different criteria to define infection status, and compared HpNGC and positive cases regarding gastric cancer risk factors. METHODS: Cases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data on H. pylori infection status determined by serologic test were included. HpNGC was reclassified as positive (eight studies) when cases presented CagA markers (four studies), gastric atrophy (six studies), or advanced stage at diagnosis (three studies), and were compared with positive cases. A two-stage approach (random-effects models) was used to pool study-specific prevalence and adjusted odds ratios (OR). RESULTS: Among non-cardia cases, the pooled prevalence of HpNGC was 22.4% (n = 166/853) and decreased to 7.0% (n = 55) when considering CagA status; estimates for all criteria were 21.8% (n = 276/1,325) and 6.6% (n = 97), respectively. HpNGC had a family history of gastric cancer more often [OR = 2.18; 95% confidence interval (CI), 1.03-4.61] and were current smokers (OR = 2.16; 95% CI, 0.52-9.02). CONCLUSION: This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives. IMPACT: Our results support that H. pylori infection is present in most non-cardia gastric cancers, and suggest that HpNGC may have distinct patterns of exposure to other risk factors.

Real-time EndoFaster improves Helicobacter pylori detection in chronic active gastritis.

Helicobacter pylori is the most frequent cause of chronic active gastritis (CAG), namely the first step for gastric cancer development. When infection is not detected at histology, another test is advised. EndoFaster is novel device that reveal the presence of H. pylori by determining ammonium concentration in the gastric juice during endoscopy. We evaluated whether this test may improve etiological diagnosis in CAG patients. In 595 consecutive patients who underwent upper endoscopy gastric juice was analysed with EndoFaster and standard biopsies were taken. CAG with typical bacteria was detected in 102 (17.1%) patients, and CAG without H. pylori was found in 36 (6.3%) cases. EndoFaster detected the infection in 22 (61.1%) of these patients. Neither ongoing proton pump inhibitor therapy nor previous eradication therapy affect the test accuracy. By using EndoFaster, another test to search for the infection in H. pylori-negative CAG patients may be avoided in more than 60% of cases, impacting on both patients discomfort and health resources use.

Association of Helicobacter pylori and gastric atrophy with adenocarcinoma of the esophagogastric junction in Taixing, China.

Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population-based case-control study in Taixing, China (2010-2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47-2.63). Neither CagA-positive nor VacA-positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72-3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P-trend <.001). H. pylori showed nonsignificant effect modification (P-interaction = .385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy-related cancers and guide the prevention and control of AEGJ.

Loss of Corpus-Specific Lipids in Helicobacter pylori-Induced Atrophic Gastritis.

Helicobacter pylori colonization of the stomach is a strong risk factor for the development of stomach cancer and peptic ulcer disease. In this study, we tested the hypothesis that H. pylori infection triggers alterations in gastric lipid composition. Mongolian gerbils were experimentally infected with H. pylori for 3 months. Conventional histologic staining revealed mucosal inflammation in stomachs from the H. pylori-infected animals but not in stomachs from uninfected control animals. Atrophic gastritis (a premalignant condition characterized by loss of corpus-specific parietal and chief cells), gastric mucosal hyperplasia, dysplasia, and/or gastric cancer were detected in stomachs from several infected animals. We then used imaging mass spectrometry to analyze the relative abundance and spatial distribution of gastric lipids. We detected ions corresponding to 36 distinct lipids that were differentially abundant when comparing gastric tissues from H. pylori-infected animals with tissues from uninfected animals. Liquid chromatography-tandem mass spectrometry analysis of lipid extracts from homogenized gastric tissues provided additional supportive evidence for the identification of several differentially abundant lipids. Sixteen of the differentially abundant lipids were localized mainly to the gastric corpus in stomachs from uninfected animals and were markedly reduced in abundance in stomachs from H. pylori-infected animals with severe disease (atrophic gastritis and dysplasia or gastric cancer). These findings indicate that H. pylori infection can lead to alterations in gastric lipid composition and constitute a new approach for identifying biomarkers of gastric atrophy and premalignant changes. IMPORTANCE H. pylori colonization of the stomach triggers a cascade of gastric alterations that can potentially culminate in stomach cancer. The molecular alterations that occur in gastric tissue prior to development of stomach cancer are not well understood. We demonstrate here that H. pylori-induced premalignant changes in the stomach are accompanied by extensive alterations in gastric lipid composition. These alterations are predicted to have important functional consequences relevant to H. pylori-host interactions and the pathogenesis of gastric cancer.

Serological Biomarker Panel in Diagnosis of Atrophic Gastritis and Helicobacter pylori Infection in Gastroscopy Referral Patients: Clinical Validation of the New-Generation GastroPanel® Test.

BACKGROUND/AIM: Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel® test (GP: biomarker panel of PGI, PGII, G-17, Hp IgG ELISA) that was developed in the early 2000's, was recently updated to a new-generation (unified GP) test version. This clinical validation study evaluated the diagnostic accuracy of the new-generation GP test in detection of AG and Hp among gastroscopy referral patients in a University Clinic. PATIENTS AND METHODS: Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing. RESULTS: Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κw) of 0.861 (95%CI=0.834-0.883). In ROC analysis using moderate/severe AG of the corpus (AGC2+) as the endpoint, AUC=0.952 (95%CI=0.891-1.000) and AUC=0.998 (95%CI=0.996-1.000) for PGI and PGI/PGII, respectively. Hp IgG antibody ELISA detected biopsy-confirmed Hp-infection with AUC=0.993 (95%CI=0.987-0.999). CONCLUSION: The new generation GastroPanel® is a precise test for non-invasive diagnosis of atrophic gastritis and Hp-infection in dyspeptic patients referred for diagnostic gastroscopy.

Risk factors for the development of esophageal candidiasis among patients in community hospital.

The aim of this study was to clarify risk factors for esophageal candidiasis (EC) in immunocompetent patients in a community hospital. 7736 patients who underwent esophagogastroduodenoscopy at our hospital from April 2012 to July 2018 were enrolled. The relationships between EC and the following factors: age, gender, body mass index, lifestyle, lifestyle-related diseases, medication, and endoscopic findings were analyzed. EC was observed in 184 of 7736 cases (2.4% morbidity rate). Multivariate analysis revealed that significant risk factors for the development of EC were: diabetes mellitus {odds ratio (OR): 1.52}, proton pump inhibitor (PPI) use (OR: 1.69), atrophic gastritis (AG) (OR: 1.60), advanced gastric cancer (OR: 4.66), and gastrectomy (OR: 2.32). When severe EC (Kodsi grade ≥ II) was compared to mild EC (grade I), the most significant risk factors were advanced gastric cancer (OR: 17.6) and gastrectomy (OR: 23.4). When considering the risk of AG and PPI use with EC development, the risk increased as follows: AG (OR: 1.59), PPI use (OR: 2.25), and both (OR: 3.13). PPI use, AG, advanced gastric cancer and post-gastrectomy are critical risk factors for the development of EC. We suggest close monitoring for EC development when PPIs are administered to patients with these factors.

Predictors for regression and progression of intestinal metaplasia (IM): A large population-based study from low prevalence area of gastric cancer (IM-predictor trial).

BACKGROUND: Gastric intestinal metaplasia (IM) can lead to gastric cancer. Until now, there have been limited studies of predictors for regression and progression of IM. This study aimed to determine risk factors associated with regression or progression of IM for guiding proper management and prevention of gastric cancer. METHODS: 2,025 patients undergoing gastroscopy in Thammasat University Hospital, Thailand were enrolled during September 2017-August 2019. Patients' data including baseline characteristics, laboratory results, and histopathology of gastric biopsies from University medical database were extensively reviewed. RESULTS: 2,025 patients had mean age of 61.3 years and 44.2% were males. Overall H. pylori prevalence was 47.5%. There were 1,551(76.6%) patients with chronic gastritis and 361(17.8%) with IM. Of 400 patients with chronic gastritis having follow-up endoscopy and repeated gastric biopsies, 104(26%) had persistent H. pylori infection and 27(26%) developed IM during mean follow-up time of 24 months. Persistent H. pylori infection was significantly associated with development of IM (OR 3.16, 95%CI 1.56-6.39, p = 0.001). Regression, persistence, and progression of IM were demonstrated in 57.3%, 39.2%, and 3.5% of patients, respectively. Age >65 years, persistent H. pylori infection, and diabetes mellitus were significantly associated with persistent IM or progression to dysplasia with OR 2.47(95%CI 1.33-4.61, p = 0.004), OR 2.64(95%CI 1.13-6.18, p = 0.025), and OR 2.54(95%CI 1.16-5.54, p = 0.019), respectively. Patients without H. pylori infection had more IM regression than patients with persistent infection (60.4%vs.39.4%, p = 0.035). Patients with persistent H. pylori infection significantly had higher IM progression to dysplasia (15.2%vs.2.1%; OR 11.15, 95%CI 1.18-105.24, p = 0.035) than noninfected. During 24 months of study, 30 patients (1.5%) were diagnosed with gastric cancer. CONCLUSION: Regression of IM could be achieved by successful H. pylori eradication. Persistent H. pylori infection was significantly associated with development and progression of IM to dysplasia. Age >65 years and diabetes mellitus were also significant predictors for IM progression.

Cytokine TGF-ß1, TNF-α, IFN-γ and IL-6 Gene Polymorphisms and Localization of Premalignant Gastric Lesions in Immunohistochemically H. pylori-negative Patients.

Background: Cytokines and their gene variants are proven to play a role in pathogenic gastritis and carcinogenesis. The study assesses associations of the cytokine gene polymorphisms with extension of atrophic gastritis/intestinal metaplasia (AGIM) in patients without Helicobacter pylori infection on immunohistochemistry study. Methods: 224 adult consecutive patients undergoing an upper digestive endoscopy were included and grouped according to localization of AGIM: 37 patients with antrum-limited AGIM, 21 corpus-limited AGIM, 15 extended-AGIM (antrum and corpus) and 151 patients had no AGIM. Medical records of the patients were checked and a structured direct interview was applied in order to collect clinical data, including digestive symptoms. In all cases, IFN-γ +874T>A, TGF-ß1 +869T>C, TNF-α-308G>A and -238G>A, and IL-6 -174C>G polymorphisms were genotyped. Results: The mean age was significantly higher in the AGIM group, while the comorbidies were similar among patients with different localization of lesions or in patients without AGIM. There were no significant differences in digestive symptoms, nor in the consumption of non-steroidal anti-inflammatory drugs or proton pump inhibitor with the different extensions of AGIM. There was a significant association between oral anticoagulant consumption and localization of AGIM (P = 0.042), frequency being higher among patients with corpus-limited AGIM than those with no AGIM (P = 0.007, adjusted P = 0.041). TGF-ß1 +869T>C was less frequent among patients with corpus-limited AGIM (n=7, 33.3%) and extended AGIM (n=5, 33.3%) than in antrum-limited AGIM (n=25, 67.6%). There were no other significant differences regarding variant and wild genotype frequencies of IFN-γ +874T>A (86.5%, 81.0%, 86.7%, p=0.814), TNF-α-308G>A (35.1%, 28.6%, 53.3%, p=0.48) and IL-6 -174C>G (70.3%. 61.9%, 73.3% p=0.656) among patients with antrum-limited, corpus-limited or extended AGIM. TGF-ß1 +869T>C was associated with a decreased risk for corpus-affected AGIM (adjusted odds ratio: 0.42, 95% confidence interval: 0.19-0.93, P = 0.032). The dominant inheritance models no revealed significant association for IFN-γ +874T>A, TNF-α-308G>A and IL-6 -174C>G gene polymorphism and the risk of localization of AGIM. Conclusion: TGF-ß1 +869T>C gene polymorphism is associated with a decreased risk for corporeal localization of premalignant lesions, while IFN-γ +874T>A, TNF-α-308G>A and IL-6 -174C>G are not associated with the risk for AGIM in immunohistochemically H. pylori negative patients.

Gastric microbiota composition in patients with corpus atrophic gastritis.

BACKGROUND: In corpus atrophic gastritis (CAG), hypochlorhydria makes plausible the overgrowth of intragastric bacteria, whose role in gastric carcinogenesis is under debate. AIMS: To characterize the antrum/corpus composition of the gastric bacterial microbiota in CAG patients compared to controls without CAG. METHODS: A cross-sectional monocentric study on consecutive patients with known histological diagnosis of CAG undergoing gastroscopy for gastric cancer surveillance and patients without CAG undergoing gastroscopy for dyspepsia or anemia (108 biopsies from 55 patients, median age 61.5). Genomic DNA from one antral and one corpus biopsy from each case (n = 23) and control (n = 32) was extracted. Gastric microbiota was assessed by sequencing hypervariable regions of the 16SrRNA gene. RESULTS: Bacterial abundance and diversity were significantly lower in CAG cases than in controls (p < 0.001). Firmicutes were more frequent in cases, Bacteroidetes and Fusobacteria in controls (p < 0.0001). Streptococcaceae were more abundant in cases (p < 0.0001), Prevotellaceae in controls (p < 0.0001). The genus Streptococcus was positively correlated with severe OLGA/OLGIM stages linked to a higher risk of gastric cancer. CONCLUSION: Gastric bacterial microbiota in CAG showed a reduced abundance and complexity but was characterized by higher colonization of Firmicutes, in particular Streptococcus, increased in subjects with severe atrophy/metaplasia stages at higher risk of gastric cancer.

Gastritis: The clinico-pathological spectrum.

The inflammatory spectrum of gastric diseases includes different clinico-pathological entities, the etiology of which was recently established in the international Kyoto classification. A diagnosis of gastritis combines the information resulting form the gross examination (endoscopy) and histology (microscopy). It is important to consider the anatomical/functional heterogeneity of the gastric mucosa when obtaining representative mucosal biopsy samples. Gastritis includes self-limiting and non-self-limiting (long-standing) inflammatory diseases, and the latter are epidemiologically, biologically and clinically linked to the onset of gastric cancer (i.e. "inflammation-associated cancer"). Different biological models of inflammation-associated gastric oncogenesis have been proposed. Helicobacter pylori (H. pylori) gastritis is the most prevalent worldwide, and H. pylori is classified as a first-class carcinogen. On these bases, eradicating H. pylori is mandatory for the primary prevention of gastric cancer. Non-self-limiting gastritis may also be triggered by the immune-mediated destruction of gastric parietal cells, resulting in autoimmune gastritis. In both H. pylori-related and autoimmune gastritis, the non-self-limiting inflammation results in atrophy of the gastric mucosa, which is the main factor promoting gastric cancer. Long-term follow-up studies consistently demonstrate the prognostic impact of the histological staging of gastritis in gastric cancer secondary prevention strategies.

Modulation of gastrointestinal bacterial in chronic atrophic gastritis model rats by Chinese and west medicine intervention.

Chronic atrophic gastritis (CAG) is well-known related with multiple pathogenic factors and normally therapies comprised by western or Chinese medicines. The present study was designed to identify the bacterial community characterized by 16S rRNA amplicon sequencing and determine the modulate affection of bacterial composition response western and Chinese medicine Qinghuayin (QHY) as well as antibiotic on model rats. The result shown the overall structure alteration of bacterial appeared under medicine intervened, antibiotic caused a marked depletion in bacterial diversity and richness. The enrichments of Firmicutes (85.1-90.7%) in antibiotic-free converts into Bacteroidetes (30.7-34.6%) in antibiotic-added model rat were demonstrated. Firmicutes as the most dominant phylum in antibiotic-free treatments and significantly decreased till 21.9-68.5% in antibiotic-added treatments. Especially QHY-treated rats showed highest RA of Firmicutes (90.7%) and the amelioration of CAG using QHY attributed by beneficial bacterial enrichment, especially Ruminococcus, Lactobacillus and Bifidobacterium. In addition, alpha and beta diversity analysis also demonstrated the clear dispersion and aggregation that revealed the alteration and steady of bacterial community structures. In summary, QHY has potential application value in the treatment of CAG, which attributed to close relation with the modulatory of internal bacterial communities.

A retrospective study assessing the acceleration effect of type I Helicobacter pylori infection on the progress of atrophic gastritis.

Based on the antibody typing classification, Helicobacter pylori infection can be divided into type I H. pylori infection and type II H. pylori infection. To observe the effects of different H. pylori infection types on the distribution of histopathological characteristics and the levels of three items of serum gastric function (PG I, PG II, G-17). 1175 cases from October 2018 to February 2020 were collected with ratio 1:2. All patients were performed with 14C-Urea breath test (14C-UBT), H. pylori antibody typing classification, three items of serum gastric function detection, painless gastroscopy, pathological examination, etc. According to H. pylori antibody typing classification, patients were divided into three groups: type I H. pylori infection group, type II H. pylori infection group and control group. Significant difference existed among type I H. pylori infection group, type II H. pylori infection group and control group in inflammation and activity (χ2 = 165.43, 354.88, P all < 0.01). The proportion of three groups in OLGA staging had statistic difference (χ2 = 67.99, P all < 0.01); Compared with type II H. pylori infection group and control group, the level of pepsinogen I, pepsinogen II, gastrin17 in type I H. pylori infection group increased, and PG I/PG II ratio (PG I/PG II ratio, PGR) decreased, which was statistically significant (χ2 = 35.08, 166.24, 134.21, 141.19; P all < 0.01). Type I H. pylori infection worsened the severity of gastric mucosal inflammation and activity. H. pylori infection was prone to induce atrophy of gastric mucosa, while type I H. pylori infection played a key role in promoting the progress of atrophic gastritis and affected the level of serum gastric function. The study indicated that the eradication of H. pylori should be treated individually.

Inflammation-Associated Senescence Promotes Helicobacter pylori-Induced Atrophic Gastritis.

BACKGROUND & AIMS: The association between cellular senescence and Helicobacter pylori-induced atrophic gastritis is not clear. Here, we explore the role of cellular senescence in H pylori-induced atrophic gastritis and the underlying mechanism. METHODS: C57BL/6J mice were infected with H pylori for biological and mechanistic studies in vivo. Gastric precancerous lesions from patients and mouse models were collected and analyzed using senescence-associated beta-galactosidase, Sudan Black B, and immunohistochemical staining to analyze senescent cells, signaling pathways, and H pylori infection. Chromatin immunoprecipitation, luciferase reporter assays, and other techniques were used to explore the underlying mechanism in vitro. RESULTS: Gastric mucosa atrophy was highly associated with cellular senescence. H pylori promoted gastric epithelial cell senescence in vitro and in vivo in a manner that depended on C-X-C motif chemokine receptor 2 (CXCR2) signaling. Interestingly, H pylori infection not only up-regulated the expression of CXCR2 ligands, C-X-C motif chemokine ligands 1 and 8, but also transcriptionally up-regulated the expression of CXCR2 via the nuclear factor-κB subunit 1 directly. In addition, CXCR2 formed a positive feedback loop with p53 to continually enhance senescence. Pharmaceutical inhibition of CXCR2 in an H pylori-infected mouse model attenuated mucosal senescence and atrophy, and delayed further precancerous lesion progression. CONCLUSIONS: Our study showed a new mechanism of H pylori-induced atrophic gastritis through CXCR2-mediated cellular senescence. Inhibition of CXCR2 signaling is suggested as a potential preventive therapy for targeting H pylori-induced atrophic gastritis. GEO data set accession numbers: GSE47797 and GSE3556.