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Helicobacter pylori (H. pylori) infection and autoimmune inflammation of the gastric mucosa are recognized as the leading etiological factors of chronic atrophic gastritis. The mechanisms of atrophy formation and progression with the risk of gastric cancer development are heterogeneous, which requires a deeper study of the molecular mechanisms of relationship, peculiarities of the course of autoimmune gastritis both in combination with H. pylori and after eradication, as well as without H. pylori infection (naïve AIG). This article presents the specific molecular and cellular patterns in the formation of these related conditions.

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.

Fundamental treatments for autoimmune gastritis (AIG) have not yet been established; thus, analyzing AIG pathogenesis in detail to obtain useful information for prognosis prediction and treatment is crucial. This study explored bacteria involved in AIG pathogenesis by focusing on the gastric microbiota composition. Gastric biopsy tissues were collected endoscopically from the gastric corpus and antrum of patients with AIG and chronic gastritis. Total DNA was extracted from gastric biopsy specimens and used for 16S rRNA gene amplicon sequencing analysis. Principal coordinate analysis of diversity using the weighted UniFrac distance revealed that following Helicobacter pylori eradication, the gastric bacterial composition of patients with AIG differed significantly from that of patients with chronic gastritis, exhibiting decreased Shannon index, Pielou’s evenness, and Simpson index of alpha diversity. The gastric microbiota of patients with AIG was characterized by an increased abundance of the genus Streptococcus and a reduced abundance of the genus Prevotella compared with that of patients with chronic gastritis.

H. pylori drug-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. For some bacterial species it has been demonstrated that fatty acids have a growth inhibitory effect. Our main aim was to assess the ability of docosahexaenoic acid (DHA) to inhibit H. pylori growth both in vitro and in a mouse model. The effectiveness of standard therapy (ST) in combination with DHA on H. pylori eradication and recurrence prevention success was also investigated. The effects of DHA on H. pylori growth were analyzed in an in vitro dose-response study and n in vivo model. We analized the ability of H. pylori to colonize mice gastric mucosa following DHA, ST or a combination of both treatments. Our data demonstrate that DHA decreases H. pylori growth in vitro in a dose-dependent manner. Furthermore, DHA inhibits H. pylori gastric colonization in vivo as well as decreases mouse gastric mucosa inflammation. Addition of DHA to ST was also associated with lower H. pylori infection recurrence in the mouse model. In conclusion, DHA is an inhibitor of H. pylori growth and its ability to colonize mouse stomach. DHA treatment is also associated with a lower recurrence of H. pylori infection in combination with ST. These observations pave the way to consider DHA as an adjunct agent in H. pylori eradication treatment.

Background and aims: A number of Helicobacter pylori outer membrane proteins (OMPs) undergo phase variations. This study examined the relation between OMP phase variations and clinical outcome. Methods: Expression of H pylori BabA, BabB, SabA, and OipA proteins was determined by immunoblot. Multiple regression analysis was performed to determine the relation among OMP expression, clinical outcome, and mucosal histology. Results:H pylori were cultured from 200 patients (80 with gastritis, 80 with duodenal ulcer (DU), and 40 with gastric cancer). The most reliable results were obtained using cultures from single colonies of low passage number. Stability of expression with passage varied with OipA > BabA > BabB > SabA. OipA positive status was significantly associated with the presence of DU and gastric cancer, high H pylori density, and severe neutrophil infiltration. SabA positive status was associated with gastric cancer, intestinal metaplasia, and corpus atrophy, and negatively associated with DU and neutrophil infiltration. The Sydney system underestimated the prevalence of intestinal metaplasia/atrophy compared with systems using proximal and distal corpus biopsies. SabA expression dramatically decreased following exposure of H pylori to pH 5.0 for two hours. Conclusions: SabA expression frequently switched on or off, suggesting that SabA expression can rapidly respond to changing conditions in the stomach or in different regions of the stomach. SabA positive status was inversely related to the ability of the stomach to secrete acid, suggesting that its expression may be regulated by changes in acid secretion and/or in antigens expressed by the atrophic mucosa.

Despite being one of the most studied cancer-related infections, the relationship between Helicobacter pylori infection and gastric adenocarcinoma (GC) remains, in some points, obscure. Based on a critical analysis of the available literature regarding stomach microbiota, we aimed to shed light to a possible new interpretation of the current understanding about the Helicobacter pylori-related GC carcinogenesis. We analyzed data from the literature on Helicobacter pylori and other potential carcinogenic pathogens, in both benignant conditions and gastric adenocarcinoma. Helicobacter pylori is the dominant microorganism in benignant conditions as non-complicated gastritis. In atrophic gastritis, metaplasia and, mainly, in gastric adenocarcinoma, a strong reduction in Helicobacter pylori abundance, and increased occurrence of other microorganisms is strongly demonstrated by metagenomic experiments. While causing peptic disease and keeping the stomach’s high acidity, Helicobacter pylori infection avoids gastric infection by carcinogenic intestinal microbiota. Nevertheless, Helicobacter pylori persistence may also provoke an atrophic gastritis, a condition that causes its own decline, due to a microenvironment modification, including reduced acidity, resulting in Helicobacter pylori substitution by a cancer-prone microbiota. This new interpretation might result in a dramatic modification on clinical management of Helicobacter pylori-related gastric disease.

Background Helicobacter pylori ( H. pylori ) infection was identified as a substantial risk factor for gastric cancer development, but the eradication of H. pylori did not necessarily lead to a reduction in the incidence of gastric cancer. N on-Helicobacter pylori (non-H. pylori) bacteria in the stomach are involved in the transformation of gastritis carcinoma. The aim of this study was to characterize the microbiome composition of the gastric mucosa and its functions in non-H. pylori (H. pylori -negative) patients with chronic atrophic gastritis (CAG) and chronic non-atrophic gastritis (CNAG). Methods Fourteen CNAG samples and twenty-three CAG samples were collected. The composition of the gastric microbiome was analyzed using 16 S rDNA gene sequencing. The bioinformatic analysis was performed using alpha and beta diversity analyses, PICRUSt2, and linear discriminant analysis effect size (LEfSe). Results The two groups shared the same most abundant bacterial phyla (Pseudomonadota, Bacillota, Actinomycetota, and Bacteroidota). The top 5 most abundant bacterial genera in the CAG group were Sphingomonas , Ralstonia , Brevundimonas , Methyloversatilis , and Pseudomonas. In the CNAG group, the top genera were Brevundimonas , Ralstonia , Sphingomonas , Methyloversatilis , and Acinetobacter . Differential analysis revealed distinct genera between groups: the CAG group showed enrichment in Sphingomonas , Ralstonia , Bradyrhizobium , Roseateles , and Acidithiobacillus , while the CNAG group was enriched in Brevundimonas , Rhodococcus , Hydrogenophaga , Bacteroides , and Leifsonia ( p  < 0.05). Sphingomonas exhibited a positive correlation with Acidithiobacillus but negative correlations with B revundimonas , Hydrogenophaga , and Leifsonia. Pathways related to xenobiotic biodegradation, metabolism, signal transduction, cofactor/vitamin metabolism, cancer, infectious diseases, and digestive system were enriched in the CAG group. In contrast, the CNAG group showed enrichment in amino acid metabolism, translation, replication/repair, and terpenoid/polyketide metabolism. Conclusion Gastric mucosal microbiota dysbiosis and functional shifts are significantly associated with chronic atrophic gastritis. Taxa such as Sphingomonas and Ralstonia , enriched in CAG patients, may indicate microbial signatures associated with early atrophic transition and provide candidates for further mechanistic validation.

Background and aims: The incidence of gastric cancer in Japan is four times higher than in the UK. It usually arises in a stomach with corpus predominant or pangastritis that has undergone extensive atrophy and intestinal metaplasia. We hypothesised that a Japanese population would have a more severe gastritis with a corpus predominant or pangastritis pattern and a greater degree of atrophy and intestinal metaplasia than that found in the UK. To test this we designed a comparative trial. Methods: A total of 252 age matched consecutive patients were recruited from the endoscopy services in Leeds and Tokyo. In each centre, 21 patients were prospectively selected from each decennial, between the ages of 20–80 years. All had epigastric discomfort as their predominant symptom. Patients with peptic ulcer, cancer, and oesophagitis were excluded. Five gastric biopsies were examined by two histopathologists using the updated Sydney system. Helicobacter pylori infection was assessed by histology and culture of biopsies and enzyme linked immunosorbent assay and immunoblot of plasma. Results: Gastritis was found by both pathologists in 59 (47%) UK and 76 (60%) Japanese patients (χ2 test, p = 0.04). In those patients with gastritis, corpus predominant or pangastritis was commoner in the Japanese (63% Japan v 36% in the UK (χ2 test, p = 0.003) Atrophy and intestinal metaplasia were more extensive and severe (Mann-Whitney U test, p<0.001) and chronic inflammation and polymorph activity were also greater, especially in the corpus (Mann-Whitney U test, p<0.001). Fifty three of 59 UK gastritis patients (90%) and 67/76 (88%) (χ2 test, p = 1) Japanese gastritis patients were positive for H pylori. Using a previously described “gastric cancer risk index” among H pylori positive patients, there were significantly more Japanese than UK subjects with a “high risk” score. Conclusion: In Japanese as opposed to English patients, gastritis is more prevalent and severe with more corpus predominant atrophy and intestinal metaplasia. These differences may partially explain the higher incidence of gastric cancer in Japan.

To establish optimal cutoff values for serologic diagnosis of fundic atrophy in a high-risk area for oesophageal squamous cell carcinoma and gastric cancer with high prevalence of Helicobacter pylori (H. pylori) in Northern Iran, we performed an endoscopy-room-based validation study. We measured serum pepsinogens I (PGI) and II (PGII), gastrin 17 (G-17), and antibodies against whole H. pylori, or cytotoxin-associated gene A (CagA) antigen among 309 consecutive patients in two major endoscopy clinics in northeastern Iran. Updated Sydney System was used as histology gold standard. Areas under curves (AUCs), optimal cutoff and predictive values were calculated for serum biomarkers against the histology. 309 persons were recruited (mean age: 63.5 years old, 59.5% female). 84.5% were H. pylori positive and 77.5% were CagA positive. 21 fundic atrophy and 101 nonatrophic pangastritis were diagnosed. The best cutoff values in fundic atrophy assessment were calculated at PGI<56 µg/l (sensitivity: 61.9%, specificity: 94.8%) and PGI/PGII ratio<5 (sensitivity: 75.0%, specificity: 91.0%). A serum G-17<2.6 pmol/l or G-17>40 pmol/l was 81% sensitive and 73.3% specific for diagnosing fundic atrophy. At cutoff concentration of 11.8 µg/l, PGII showed 84.2% sensitivity and 45.4% specificity to distinguish nonatrophic pangastritis. Exclusion of nonatrophic pangastritis enhanced diagnostic ability of PGI/PGII ratio (from AUC = 0.66 to 0.90) but did not affect AUC of PGI. After restricting study samples to those with PGII<11.8, the sensitivity of using PGI<56 to define fundic atrophy increased to 83.3% (95%CI 51.6-97.9) and its specificity decreased to 88.8% (95%CI 80.8-94.3). Among endoscopy clinic patients, PGII is a sensitive marker for extension of nonatrophic gastritis toward the corpus. PGI is a stable biomarker in assessment of fundic atrophy and has similar accuracy to PGI/PGII ratio among populations with prevalent nonatrophic pangastritis.

ObjectiveGastric carcinoma development is triggered by Helicobacter pylori. Chronic H. pylori infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy. Our aim was to evaluate the composition of the gastric microbiota in chronic gastritis and in gastric carcinoma.DesignThe gastric microbiota was retrospectively investigated in 54 patients with gastric carcinoma and 81 patients with chronic gastritis by 16S rRNA gene profiling, using next-generation sequencing. Differences in microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Associations between the most relevant taxa and clinical diagnosis were validated by real-time quantitative PCR. Predictive functional profiling of microbial communities was obtained with PICRUSt.ResultsThe gastric carcinoma microbiota was characterised by reduced microbial diversity, by decreased abundance of Helicobacter and by the enrichment of other bacterial genera, mostly represented by intestinal commensals. The combination of these taxa into a microbial dysbiosis index revealed that dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Analysis of the functional features of the microbiota was compatible with the presence of a nitrosating microbial community in carcinoma. The major observations were confirmed in validation cohorts from different geographic origins.ConclusionsDetailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis.