Although millions of people have been infected by Helicobacter pylori (H. pylori), only a small proportion of infected individuals will develop adverse outcomes, ranging from chronic gastritis to gastric cancer. Advanced development of the disease has been well-linked with chronic inflammation, which is significantly impacted by the adaptive and humoral immunity response. From the perspective of cellular immunity, this review aims to clarify the intricate axis between IL-17, IL-21, and IL-23 in H. pylori-related diseases and the pathogenesis of inflammatory gastrointestinal diseases. CD4⁺ helper T (Th)-17 cells, with the hallmark pleiotropic cytokine IL-17, can affect antimicrobial activity and the pathogenic immune response in the gut environment. These circumstances cannot be separated, as the existence of affiliated cytokines, including IL-21 and IL-23, help maintain Th17 and accommodate humoral immune cells. Comprehensive understanding of the dynamic interaction between molecular host responses in H. pylori-related diseases and the inflammation process may facilitate further development of immune-based therapy.

Helicobacter pylori disturbs the stomach lining during long-term colonization of its human host, with sequelae including ulcers and gastric cancer^1,2. Numerous H. pylori virulence factors have been identified, showing extensive geographic variation¹. Here we identify a ‘Hardy’ ecospecies of H. pylori that shares the ancestry of ‘Ubiquitous’ H. pylori from the same region in most of the genome but has nearly fixed single-nucleotide polymorphism differences in 100 genes, many of which encode outer membrane proteins and host interaction factors. Most Hardy strains have a second urease, which uses iron as a cofactor rather than nickel³, and two additional copies of the vacuolating cytotoxin VacA. Hardy strains currently have a limited distribution, including in Indigenous populations in Siberia and the Americas and in lineages that have jumped from humans to other mammals. Analysis of polymorphism data implies that Hardy and Ubiquitous coexisted in the stomachs of modern humans since before we left Africa and that both were dispersed around the world by our migrations. Our results also show that highly distinct adaptive strategies can arise and be maintained stably within bacterial populations, even in the presence of continuous genetic exchange between strains.

Background: We evaluated the microbiota in the stomach of Gastroesophageal Reflux Disease (GERD) patients. We compared Erosive Reflux Disease (ERD) to gastritis and Non-erosive Reflux Disease (NERD) subjects by 16S rRNA approach on gastric biopsy specimens. A total of 197 subjects were included consisting of gastritis (68; 34.52%), ERD (55; 27.92%), and NERD (74; 37.56%). After quality filtering, 187 samples were included for OTU analysis using Qiime2. Results: We observed a significant difference in alpha diversity (Shannon and Simpson indexes were P = 0.0016 and P = 0.017, respectively). A significant decrease in alpha diversity index was observed in NERD with Helicobacter pylori (H. pylori)-positive subjects than in gastritis (Simpson index P = 0.022; Shannon index P = 0.029), indicating a significant influence of H. pylori on the diversity in the stomach despite the diseases. In H. pylori-negative samples, alpha diversity measurement by the abundance coverage estimates (ACE) and Fisher Test revealed that ERD had significantly lower richness than gastritis and NERD groups (P = 0.00012 and P = 0.00043, respectively). Anaerobacillus sp. could only be found in ERD patients by LEFse analysis. Conclusions: The presence of ERD could alter microbiome diversity. A negative correlation between H. pylori and ERD is shown in this microbiome study but not in NERD.

Dyspepsia still becomes a major challenge in upper gastrointestinal disease in Indonesia. This disease often correlated with Helicobacter pylori infection. However, the prevalence of this bacterium is generally low in Indonesia. Therefore, several considerations should be taken into consideration during the management of dyspepsia and H. pylori infection. “Management of dyspepsia and H. pylori infection in Indonesia: The Indonesian consensus report” comprises information gathered from 22 gastroenterology centers across Indonesia. The experts gathered to evolve a consensus, that consists of the statements, grades of recommendations, evidence levels, and rationales for the dyspepsia and H. pylori infection management for daily clinical practice. The report explains several aspects from the updated epidemiology information to comprehensive management therapy. After the experts worked together on all statements in the recommendations, the results are presented with the final agreement as a consensus to help clinicians in understanding, diagnosing, and treating dyspepsia and H. pylori infection patients in daily clinical practice in Indonesia.

Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as pbp1a, rdxA, ribF, fur, gyrA, gyrB, 23S rRNA, and infB) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher’s exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance (p = 0.000018) but not in locus A2146G (p = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) (p = 0.002) and N87K (p = 0.002) of gyrA was associated with levofloxacin resistance. Mutations in locus A343V (p = 0.041) of gyrB also showed a significant association. Meanwhile, in the pbp1a gene, several mutations might explain the resistance; they were G594fs (p = 0.036), K306R (p = 0.036), N562Y (p = 0.0006), and V45I (p = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in rdxA genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in H. pylori.

Background: Biofilm formation in Helicobacter pylori (H. pylori) helps bacteria survive antibiotic exposure and supports bacterial colonization and persistence in the stomach. Most of the published articles have focused on one aspect of the biofilm. Therefore, we conducted the current study to better understand the mechanism of biofilm formation, how the biofilm contributes to antibiotic resistance, and how the biofilm modifies the medication delivery mechanism. Methods: We conducted a literature review analysis of the published articles on the Helicobacter pylori biofilm between 1998 and 2024 from the PubMed database to retrieve eligible articles. After applying the inclusion and exclusion criteria, two hundred and seventy-three articles were eligible for our study. Results: The results showed that biofilm formation starts as adhesion and progresses through micro-colonies, maturation, and dispersion in a planktonic form. Moreover, specific genes modulate each phase of biofilm formation. Few studies have shown that mechanisms, such as quorum sensing and diffusible signal factors, enhance coordination among bacteria when switching from biofilm to planktonic states. Different protein expressions were also observed between planktonic and biofilm strains, and the biofilm architecture was supported by exopolysaccharides, extracellular DNA, and outer membrane vesicles. Conclusions: This infrastructure is responsible for the increased survival of bacteria, especially in harsh environments or in the presence of antibiotics. Therefore, understanding the biofilm formation for H. pylori is crucial. This study illustrates biofilm formation in H. pylori to help improve the treatment of H. pylori infection.