Progression Of Chronic Gastritis Research Articles

The mutual interactions among Helicobacter pylori, chronic gastritis, and the gut microbiota: a population-based study in Jinjiang, Fujian.

Helicobacter pylori (H. pylori) is a type of bacteria that infects the stomach lining, and it is a major cause of chronic gastritis (CG). H. pylori infection can influence the composition of the gastric microbiota. Additionally, alterations in the gut microbiome have been associated with various health conditions, including gastrointestinal disorders. The dysbiosis in gut microbiota of human is associated with the decreased secretion of gastric acid. Chronic atrophic gastritis (CAG) and H. pylori infection are also causes of reduced gastric acid secretion. However, the specific details of how H. pylori infection and CG, especially for CAG, influence the gut microbiome can vary and are still an area of ongoing investigation. The incidence of CAG and infection rate of H. pylori has obvious regional characteristics, and Fujian Province in China is a high incidence area of CAG as well as H. pylori infection. We aimed to characterize the microbial changes and find potential diagnostic markers associated with infection of H. pylori as well as CG of subjects in Jinjiang City, Fujian Province, China. Enrollment involved sequencing the 16S rRNA gene in fecal samples from 176 cases, adhering to stringent inclusion and exclusion criteria. For our study, we included healthy volunteers (Normal), individuals with chronic non-atrophic gastritis (CNAG), and those with CAG from Fujian, China. The aim was to assess gut microbiome dysbiosis based on various histopathological features. QIIME and LEfSe analyses were performed. There were 176 cases, comprising 126 individuals who tested negative for H. pylori and 50 who tested positive defined by C14 urea breath tests and histopathological findings in biopsies obtained through endoscopy. CAG was also staged by applying OLGIM system. When merging the outcomes from 16S rRNA gene sequencing results, there were no notable variations in alpha diversity among the following groups: Normal, CNAG, and CAG; OLGIM I and OLGIM II; and H. pylori positive [Hp (+)] and H. pylori negative [Hp (-)] groups. Beta diversity among different groups show significant separation through the NMDS diagrams. LEfSe analyses confirmed 2, 3, and 6 bacterial species were in abundance in the Normal, CNAG, and CAG groups; 26 and 2 species in the OLGIM I and OLGIM II group; 22 significant phylotypes were identified in Hp (+) and Hp (-) group, 21 and 1, respectively; 9 bacterial species exhibited significant differences between individuals with CG who were Hp (+) and those who were Hp (-). The study uncovered notable distinctions in the characteristics of gut microbiota among the following groups: Normal, CNAG, and CAG; OLGIM I and OLGIM II; and Hp (+) and Hp (-) groups. Through the analysis of H. pylori infection in CNAG and CAG groups, we found the gut microbiota characteristics of different group show significant difference because of H. pylori infection. Several bacterial genera could potentially serve as diagnostic markers for H. pylori infection and the progression of CG.

Coptis, Pinellia, and Scutellaria as a promising new drug combination for treatment of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer. To identify efficient therapeutic agents or strategies that can treat H. pylori infection. We performed literature analysis, experimental validation, and network pharmacology. First, traditional Chinese medicine (TCM) prescriptions for the treatment of H. pylori infection were obtained from the China National Knowledge Infrastructure, China Biology Medicine, China Science and Technology Journal Database, and WanFang databases. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). Next, we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions. Then, an H. pylori-associated chronic mouse model of gastritis was established. The antibacterial properties and anti-inflammatory potential of the core drug combination were evaluated by the rapid urease test, modified Warthin-Starry silver staining, histopathological analysis, and enzyme linked immunosorbent assay. Finally, the active compounds, hub targets, and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology. The TCM treatment of H. pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing, bitter descending, cold and warm drugs. The combination of Coptis, Pinellia, and Scutellaria (CPS) was identified as the core drug combination from 207 prescriptions and 168 herbs. This drug combination eradicated H. pylori, alleviated the gastric pathology induced by H. pylori infection, and reduced the expression levels of tumor necrosis factor-α (P = 0.024) and interleukin-1β (P = 0.001). Moreover, a total of 35 compounds and 2807 targets of CPS were identified using online databases. Nine key compounds (tenaxin I, neobaicalein, norwogonin, skullcapflavone II, baicalein, 5,8,2'-trihydroxy-7-methoxyflavone, acacetin, panicolin, and wogonin) and nine hub target proteins (EGFR, PTGS2, STAT3, MAPK3, MAPK8, HSP90AA1, MAPK1, MMP9, and MTOR) were further explored. Seventy-seven signaling pathways were correlated with H. pylori-induced inflammation and carcinogenesis. In summary, we showed that CPS is the core drug combination for treating H. pylori infection. Animal experiments demonstrated that CPS has bacteriostatic properties and can reduce the release of inflammatory cytokines in the gastric mucosa. Network pharmacology predictions further revealed that CPS showed complex chemical compositions with multi-target and multi-pathway regulatory mechanisms. Although the results derived from network pharmacology are not necessarily comprehensive, they still expand our understanding of CPS for treating H. pylori infection.

Evodiamine Inhibits Helicobacter pylori Growth and Helicobacter pylori-Induced Inflammation.

Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of Evodia rutaecarpa, evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against H. pylori is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on H. pylori growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on H. pylori-induced inflammation were investigated in vitr. Results of this study showed the growth of the H. pylori reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expressions of replication and transcription machineries of H. pylori. Treatment of evodiamine also induced downregulation of urease and diminished translocation of cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) proteins into gastric adenocarcinoma (AGS) cells. This may be resulted from the reduction of CagA and VacA expressions as well as the type IV secretion system (T4SS) components and secretion system subunit protein A (SecA) protein which are involved in translocation of CagA and VacA into host cells, respectively. In particular, evodiamine inhibited the activation of signaling proteins such as the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway induced by H. pylori infection. It consequently might contribute to reduction of interleukin (IL)-8 production in AGS cells. Collectively, these results suggest anti-bacterial and anti-inflammatory effects of evodiamine against H. pylori.

The role of the CagA gene in the occurrence of the inflammatory response of the gastric mucosa in patients with chronic Helicobacter pylori-associated gastritis

Currently, Helicobacter pylori infection (H. pylori) is recognized as one of the most important risk factors for gastrocarcinogenesis. It is known that this infection does not directly cause neoplastic changes in the gastric mucosa, and this is due to a number of consecutive events due to the long persistence of the pathogen in the human body. The initial stage of this cascade, of course, is the inflammatory response, due to the body’s ability to adapt to extraneous infection, which is the inevitable result of the interaction of H. pylori with cells of the gastric epithelium. This direct damaging effect is enhanced by the production of vacuolating cytotoxin and the release of products of the cytotoxin-associated CagA gene, which, at a pathomorphological level, is manifested by inflammatory infiltration of the gastric mucosa (GM) to some extent. On the relationship between the degree of contamination and the activity of the inflammation of the GM in people infected with the CagA strain, today there are different, often conflicting opinions, which is why in this work we set the goal of establishing the relationship between the nature of the inflammatory response and the presence of the CagA gene in H. pylori- infected patients. The purpose of the study is to determinate the relationship between the nature of the inflammatory response and the genetic features of the H. pylori strain (CagA genotype).We examined 365 patients, among whom 40 people were included in the control group (18 women and 22 men, whose average age was 45,33±15,46 and 42,82±12,31, respectively) without any gastroenterological pathology in the anamnesis , patients with chronic non-atrophic gastritis (188 people) and chronic atrophic gastritis (137 people). A close relationship was established between the presence of the CagA gene, activity and the degree of contamination for chronic non-atrophic gastritis: for a low degree of contamination, Fisher’s exact test was = 0.002, p<0.05, for a moderate degree - 0.012, p<0.05, for a high degree - 0,012, p<0.05. Accordingly, in chronic atrophic gastritis: for a low degree of contamination Fisher’s exact test = 0.011, p<0.05, for a moderate degree - 0.003, p<0.05, for a high degree - 0.001, p<0.05. There is also a close relationship between the degree of contamination and the activity of chronic gastritis: in patients with a high degree of contamination, CG activity was determined, as a rule, for stage 2-3. In our study, the inflammatory response depended on the presence or absence of the H. pylori strain in the patient, which contains the CagA genotype, which, in our opinion, plays a key role in triggering a cascade of inflammatory changes in the GM and progression of chronic gastritis.

Immunization with Heat Shock Protein A and γ-Glutamyl Transpeptidase Induces Reduction on the Helicobacter pylori Colonization in Mice.

The human gastric pathogen Helicobacter pylori (H. pylori) is a successful colonizer of the stomach. H. pylori infection strongly correlates with the development and progression of chronic gastritis, peptic ulcer disease, and gastric malignances. Vaccination is a promising strategy for preventing H. pylori infection. In this study, we evaluated the candidate antigens heat shock protein A (HspA) and H. pylori γ-glutamyl transpeptidase (GGT) for their effectiveness in development of subunit vaccines against H. pylori infection. rHspA, rGGT, and rHspA-GGT, a fusion protein based on HspA and GGT, were constructed and separately expressed in Escherichia coli and purified. Mice were then immunized intranasally with these proteins, with or without adjuvant. Immunized mice exhibited reduced bacterial colonization in stomach. The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response, as well as a balanced Th1/Th2 cytokine response. In addition, immunofluorescence microscopy confirmed that rHspA-GGT specific rabbit antibodies were able to directly bind H. pylori in vitro. These results suggest antibodies are essential to the protective immunity associated with rHspA-GGT immunization. In summary, our results suggest HspA and GGT are promising vaccine candidates for protection against H. pylori infection.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

Su1844 The *910t>C Polymorphism of Mafk Gene is Closely Associated With the Progression of Chronic Gastritis

Su1844 The *910t>C Polymorphism of Mafk Gene is Closely Associated With the Progression of Chronic Gastritis

Su1846 A Polymorphism Rs7521584 in Pre-Mir429 and Pre-Mir200s Genes is Closely Associated With the Progression of Chronic Gastritis

[Background] A polymorphism rs7521584 is located between MIR200B and MIR 429. Recently, it has been reported that both miR200 and miR429 target c-myb gene and affect the breast cancer cell growth (Cesi V, et al.: Cell cycle 2011). One of both the miR200s and miR429 targeting genes is RIPK2, coding RICK. RICK is an important molecule for inflammation by transmitting NOD signal. Then, we attempted to clarify the association between chronic gastritis and genomic variation rs7521584G>T in Japanese population. [Materials and Methods] Gastric mucosa samples were obtained from 429 subjects with no malignancies. The rs7521584 genotype was determined by PCR-SSCP method using DNA extracted from obtained gastric mucosa. The degree of gastritis was assessed in 393 cases according to the updated Sydney system, serum pepsinogen (PG) I/II levels were measured in 117 cases. [Results] The mean age of the subjects was 59.7 years old, male/female ratio was 253/176, and H. pylori (HP) positive ratio was 63.6%. The distribution of rs7521584G>T genotype in all subjects was 153GG, 215GT and 61TT (HWE, p=0.31). The atrophic gastritis group (GA group) was defined as atrophy score >0 and metaplasia score >0. Then, the distribution of rs7521584G>T genotype in GA group (n=142) was 51GG, 66GT and 22TT. The rs7521584 minor allele frequencies in GA and non-GA groups were 39.6% and 38.2%, respectively. By logistic regression analysis after adjustment for gender, age and H. pylori (HP) infection status, rs7521584 TT homozygote has a significantly high risk for gastric mucosal atrophy (OR: 2.41, 95%CI: 1.10-5.25, p=0.027). In HP positive subjects, TT homozygote was a more significant risk factor for gastric mucosal atrophy (OR: 3.31, 95%CI: 1.35-8.12, p=0.0089). In addition, in the subjects younger than 60 years old, TT homozygote has also significant risk for gastric mucosal atrophy (OR: 3.15, 95%CI: 1.03-9.61, p=0.044). The serum PG I/II ratio was reversely correlated to the age in TT homozygote (p=0.0084 by ANOVA), whereas there was no correlation between age and PG I/II ratio in G carrier (p=0.092). [Conclusions] Our results suggest that rs7521584, in pre-miR429 and premiR200s gene, TT homozygote is a risk factor for the progression of gastric mucosal atrophy under the influence of HP infection.

Mapping Analysis of Ghrelin Producing Cells in the Human Stomach Associated with Chronic Gastritis and Early Cancers

The majority of ghrelin producing cells (GPC) are present in the fundic gland of the stomach and recognized as X/A like cells. The detailed distribution of GPC in the stomach is still unknown in healthy and pathological subjects. We investigated the detailed distribution of GPC in the stomach, especially in relation with chronic gastritis, using surgical specimens from 12 patients with early gastric cancer. Either the anterior or posterior half of the whole stomach, which was a counterpart of the tumor bearing side, was subjected for immunohistochemistry of ghrelin, and the number of total GPC were semi quantitatively evaluated as GPC score. GPC score was compared with the degree of chronic gastritis, serum ghrelin concentration and body weight. GPC was not observed in the pyloric gland, but heterogeneously distributed in the fundic gland mainly in upper body and the greater curvature. The GPC score showed about nine-fold difference, which correlated well with the degree of chronic gastritis by Sydney score (r=-0.84, P<0.001). The serum ghrelin concentration was basically determined by the GPC score (r=0.75, P=0.0047); however, the obese patients showed low serum ghrelin concentration in spite of the presence of abundant GPCs. In the low GPC score patients, serum ghrelin was constantly low regardless of their body weight. GPC was inversely correlated with progression of chronic gastritis. Its quantification using immunohistochemistry of the whole stomach was useful to comprehensively evaluate ghrelin profile.

Contribution Of Epidemiological Studies To Gastritis Immunology

Chronic gastritis, or chronic inflammation in gastric antral and/or corpus mucosa, is a common pathological condition affecting over half the general population. Progression of chronic gastritis from Helicobacter pylori infection to severe gastric mucosal atrophy usually takes decades and varies considerably from person to person. Therefore, studies of clinically selected material cannot provide a complete picture of natural evolution of the disease or its wide variability. An overview of immunological and morphological aspects of chronic gastritis in an epidemiological context, based on data from the literature and the author's studies, reveal dynamic interaction between H. pylori infection and host response to the organism's antigens, and to gastric autoantigens including gastric H+K+ ATPase. Further population and followup studies of antral and corpus gastritis at different stages of evolution are needed, in combination with new methods, to elucidate further the roles of infection, and gastric-antrum- and corpus-mucosa-related autoimmune responses, in the pathogenesis of chronic gastritis.

Progression of chronic gastritis and Helicobacter pylori. A pathological study with 20-years follow-up

Progression of chronic gastritis and Helicobacter pylori. A pathological study with 20-years follow-up

Review article: Pathogenesis of the transformation from gastritis to malignancy.

Helicobacter pylori acquisition is the main cause of chronic gastritis in humans. In up to half of the infected subjects, chronic gastritis progresses to atrophic gastritis and intestinal metaplasia. During this course, various mechanisms are triggered that may contribute to the pathogenesis of gastric cancer. Such mechanisms include the inflammation-related cascades of cytokine and free radical reactions, up- and downregulation of growth factors and their receptors, and the atrophy-related impairment of acid output and intraluminal acidity. An array of other factors may also have become significant including overgrowth of bacteria other than H. pylori in the hypochlorhydric or achlorhydric stomach, a high dietary consumption of salt, nitrate, or nitrite, smoking, deficiency of vitamins or micronutrients, influence of sex hormones, or an inherited liability of the dividing epithelial cells to gene errors. These factors may vary in effect between populations and individuals but, if active, may affect the cell genome which may further influence the course and progression of chronic gastritis, and can finally result in overt gastric neoplasia. The molecular biology of gastric cancer has revealed a spectrum of gene errors which vary in type and extent between different histological types of cancer, and between individual cases. There now is evidence that the intestinal metaplasia or the gastric epithelium in atrophic gastritis reveal signs of abnormal expression of various regulatory genes well before the appearance of gastric neoplasia. It is possible that the mechanisms leading to mutation of the genes in epithelial cells are triggered very early in the H. pylori gastritis cascade, and that atrophic gastritis and intestinal metaplasia result from these processes.

Helicobacter (Campylobacter) pylori Infestation and the Development and Progression of Chronic Gastritis: Results of Long-term Follow-up Examinations of a Random Sample

One hundred and thirty-nine subjects representing a randomly selected sample of an Estonian urban population examined endoscopically, bioptically and bacteriologically in 1979 was re-examined in 1985. In the antrum the development of superficial gastritis was clearly associated with the appearance or persistence of Helicobacter pylori (HP) infestation. The further progression of superficial gastritis could less clearly be related to HP infestation, although regression and progression of antral superficial gastritis was significantly associated with the disappearance or presence of the bacteria. The progression of atrophic antral gastritis as well as the development and progression of all body gastritis seemed unrelated to the HP infestation. It is concluded, that HP infestation is in some way involved in the appearance of the first stages of chronic gastritis, but is less related or unrelated to its further progression, which is probably determined mainly by factors other than HP.

Reduced thickness of gastric mucosa and retarded progression of chronic gastritis in patients with renal failure.

Conflicting results are reported in the literature on the structure and function of gastric mucosa in patients with chronic renal failure (CRF). In the present endoscopic study of 68 CRF patients on conservative treatment (regular dialyses or transplantations had not yet been undertaken), we sought to clarify whether CRF leads to hypertrophic or hypotrophic phenomena in gastric mucosa, as interpreted by the presence and grade of gastritis and by the thickness of the gastric mucosa. We found that the mean progression of gastritis in both antrum and body was significantly slower than expected in CFR patients, and that the thickness of both antral and body mucosa was significantly lower in CFR patients than in non-CRF controls. Furthermore, although the thickness of the oxyntic body mucosa in CRF showed a positive correlation to serum gastrin (SeGa) levels and even though 12 of the patients showed high SeGa levels corresponding to those seen in the Zollinger-Ellison synbdrome (300-1500 ng/l), the thickness of the oxyntic body mucosa in CRF patients did not exceed that seen in control subjects with normal SeGa. We conclude that CRF exerts inhibitory effects on the gastric mucosa resulting in retardation in the progression of chronic gastritis and hypotrophy of the gastric mucous membrane.