Helicobacter pylori infection is a major driver of gastric cancer, with the CagA oncoprotein promoting chronic inflammation and epithelial injury. However, the overall picture of the cytokine–receptor pathways involved in this process remains unclear. To investigate how CagA modulates epithelial signaling, we generated cagA-deletion and cagA-complemented mutants of the gerbil-adapted TN2 strain and infected AGS gastric epithelial cells for 6–48 h. We also analyzed 85 gastric biopsy specimens from a nationwide Indonesian survey. In vitro, wild-type and cagA-complemented H. pylori robustly induced IL-8, IL-1β, and TNF-α, as expected. In the CagA-positive strain, the newly identified anti-inflammatory cytokine, IL-13, was also induced. IL-13-related Fn14, a TNF receptor superfamily member, was strongly upregulated in a CagA-positive strain, whereas TNFR1 remained stable, and TNFR2 was consistently downregulated. In clinical specimens, Fn14 expression was elevated in atrophic gastritis and closely associated with cagA positivity. IL-13 expression showed a distinct pattern, increased in atrophic gastritis but unrelated to H. pylori or cagA status, instead correlating positively with TWEAK, the ligand for Fn14. Together, these findings suggest that cagA-positive H. pylori infection is associated with Fn14 upregulation, whereas H. pylori infection in general is linked to TNFR2 downregulation. IL-13-related signaling may instead reflect mucosal injury and repair responses, indicating context-dependent regulation of TNF receptor family pathways in gastric mucosal inflammation.

Accurate detection and monitoring of antimicrobial resistance (AMR) in Helicobacter pylori mainly rely on phenotypic methods and culture, which can sometimes fail when bacterial load is low or after recent treatment. We investigated whether gastric biopsies classified as H. pylori-negative by standard diagnostic techniques still contain detectable bacterial DNA, including regions linked to AMR, and assessed whether selected DNA fragments can mediate allelic exchange in vitro. Gastric biopsies from 46 dyspeptic patients in the Democratic Republic of the Congo (including 23 phenotypically positive and 23 phenotypically negative individuals) were analyzed using long-read amplicon sequencing of seven resistance-associated loci, selective whole-genome amplification (sWGA) followed by long-read sequencing of H. pylori-enriched reads, and a proof-of-concept natural transformation assay. Phenotypically negative biopsies exhibited significantly lower sequencing depth across multiple loci (including 23S rRNA, gyrA, gyrB, and pbp1A; p = 0.003-0.014), indicating a reduced H. pylori DNA burden. However, AMR-associated mutations linked to various antibiotic classes were found in both groups. sWGA enabled recovery of fragmentary H. pylori sequence data from phenotypically negative samples, including reads that map to resistance- and virulence-associated genes. In vitro, 23S rRNA A2143G amplicons from both phenotypically positive and negative biopsies produced clarithromycin-resistant transformants in strain 26695. These findings indicate that phenotypically negative gastric biopsies might contain low-abundance and fragmentary H. pylori DNA. Although certain DNA fragments can mediate allelic exchange under controlled in vitro conditions, these results do not confirm bacterial viability, active infection, or clinically relevant in vivo resistance transfer. Therefore, they should be interpreted with caution in molecular AMR surveillance and detection contexts.

Background/Objectives: Despite increasing GERD prevalence worldwide, the role of gastroduodenal microbiota in GERD phenotypes and symptom severity remains poorly understood. This study profiled mucosa-associated microbiota from the gastric antrum and duodenum across phenotypes and examined site-specific associations with symptom severity. Methods: In this cross-sectional study, forty individuals, including 26 with erosive reflux disease (ERD), 10 with non-erosive reflux disease (NERD), and 4 participants in the endoscopically normal comparator group, underwent 16S rRNA gene sequencing. Community differences were assessed using Bray-Curtis dissimilarity, differential taxa were explored by linear discriminant analysis effect size (LEfSe), and correlations with validated symptom questionnaires were evaluated. Results: Microbial community structure differed significantly between the antrum and duodenum, with Proteobacteria and Firmicutes predominating at both sites. LEfSe suggested enrichment of Streptococcus, Haemophilus, and Enterobacter in the duodenum, whereas Sphingobium, Acinetobacter, and Aquabacterium were more abundant in the antrum. The genus Helicobacter was relatively enriched in the antrum of ERD samples, whereas Streptococcus-dominant signatures were more prominent in the duodenum. Symptom severity showed stronger associations with duodenal taxa, including Fusobacterium with odynophagia, early satiety, and globus; Aquabacterium with postnatal drip and dyspnea, whereas gastric associations were fewer. Conclusions: In this small exploratory cross-sectional cohort, gastroduodenal microbiota exhibited both site-specific and phenotype-associated differences, with phenotype-related microbial variation being more evident in the duodenum than in the antrum. These hypothesis-generating findings highlight the importance of considering both anatomical context and GERD phenotype in upper gastrointestinal host-microbe interactions, and require confirmation in larger, phenotypically well-characterized cohorts.

Background:Helicobacter pylori (H. pylori) is a major gastric pathogen and class I carcinogen that causes chronic gastritis, peptic ulcer, and gastric cancer if left untreated. However, evidence on H. pylori prevalence and antimicrobial resistance in Kazakhstan, a country with a high gastric cancer burden, remains scarce. This study presents the first culture-based epidemiological investigation of H. pylori at a single center in Almaty. Materials and methods:We conducted a cross-sectional study (2024-2025) of 150 dyspeptic patients in Almaty, Kazakhstan. A subset (n = 148) underwent rapid stool antigen (RAS) testing before gastric biopsy collection. Biopsy samples were cultured, and 86 (57.3%) yielded viable H. pylori isolates. Antimicrobial susceptibility testing by the agar dilution method was performed on these 86 isolates. Demographic and clinical data were analyzed, and a regional meta-analysis was conducted using data from recent studies across Central Asia and Russia to estimate pooled prevalence and clarithromycin resistance. Results:Among 148 patients tested by RAS, 137 were positive. Resistance rates among 86 isolates were 87.2% to metronidazole, 33.7% to clarithromycin, and 3.5% to amoxicillin; no resistance was detected to minocycline or sitafloxacin. Multidrug resistance (defined as resistance to two or more antibiotics) was observed in 34.8% of isolates. The pooled H. pylori prevalence across Central Asian studies was 70% (95% CI: 59-80%), and pooled clarithromycin resistance was 29% (95% CI: 10-53%). Conclusion:This study provides the first culture-based evidence of H. pylori infection and antimicrobial resistance in Kazakhstan. The high resistance to metronidazole and clarithromycin suggests a likely lower success of standard triple therapy in Almaty. Absence of resistance to minocycline and sitafloxacin supports their use in rescue regimens. These findings highlight the urgent need for national surveillance, updated treatment guidelines, and integration of molecular resistance monitoring to improve evidence-based management of H. pylori in Central Asia.

Regional differences in the gut microbiota and CRC incidence and mortality rates are well-documented. However, studies on the microbiota associated with CRC in Indonesia remain scarce. This study aimed to chracterize the gut microbiota profile of CRC in Indonesia. We collected stool samples from 14 patients with CRC (CRC), 19 patients with non-CRC bowel diseases (non-CRC), and 16 healthy controls (HC). The gut microbiota profiles across the three groups were analyzed using 16 S rRNA gene amplicon sequencing. Data analysis was performed using several software packages: QIIME2, ANCOM-BC2, and PICRUSt2. In comparison to the non-CRC and HC groups, patients with CRC demonstrated significant differences in both alpha and beta diversity. The CRC group had lower evenness and richness than the HC group. Firmicutes and Bacteroidota were identified as the predominant phyla across all groups. The differential abundance analysis identified four beneficial genera that were substantially reduced in Indonesian CRC patients: Roseburia, Dialister, Agathobacter, and Muribaculaceae. No genera were found to be significantly enriched in CRC. Functional prediction analysis revealed multiple pathways such as mTOR, mRNA surveillance, basal transcription factors, phagosome, and proteasome, were reduced in CRC. Conversely, CRC demonstrated a significant upregulation of pathways related to lipid metabolism and the biosynthesis of flavonoids, stilbenoids, diarylheptanoids, and gingerols. Our study revealed distinct gut microbiota profiles in Indonesian CRC patients, highlighting the significance of decreased abundance of certain beneficial taxa.

Diarrheal disease remains a significant public health concern in Bhutan; however, the genomic epidemiology of the circulating diarrhoeagenic Escherichia coli (DEC) strain remains poorly understood. This study characterized the genomic diversity, antimicrobial resistance (AMR), and virulence determinants of DEC isolates using whole-genome sequencing (WGS). DEC isolates recovered from stool samples and collected through Bhutan's National Diarrheal Disease Surveillance sentinel hospitals during 2023 were identified by a multiplex polymerase chain reaction, tested for antimicrobial susceptibility using the Kirby-Bauer disc diffusion method, and sequenced on the Illumina MiSeq platform. Genomes were analyzed using the Bohra pipeline to determine pathotypes, phylogeny, multilocus sequence types, serotypes, virulence factors, and AMR genes. Of the 29 DEC isolates, 27 were confirmed by WGS and enteropathogenic E. coli (37.0%) and enteroaggregative E. coli (33.3%) were the predominant pathotypes. Isolates exhibited extensive genetic diversity, representing phylogroups A and B1 and 22 serotypes. Phenotypic resistance to β-lactams was common, with 25.9% of isolates carrying blaCTX-M-15. Virulence profiling identified diverse adhesins, toxins, iron acquisition systems, and type III secretion system components. DEC isolates in Bhutan comprise a genetically diverse population with a concerning convergence of virulence determinants and multidrug resistance. The findings underscore the strengthening of sustained genomic surveillance to monitor AMR and genomic epidemiology of bacterial pathogens.

Species-level resolution is essential to understand gastric microbiome recovery after Helicobacter pylori eradication, yet short-read 16 S rRNA approaches often obscure clinically relevant changes. Gastric biopsies from 121 adults in Bayan-Ölgii, Mongolia (71 H. pylori–positive, 50 H. pylori–negative) were analyzed, including nine paired pre- and post-eradication gastric biopsy samples collected six months apart, enabling exploratory longitudinal analysis. Full-length 16 S rRNA (V1–V9) sequencing was performed using the Oxford Nanopore platform with EMU taxonomic assignment (SILVA v138.1/NCBI RefSeq). Ecological changes were evaluated using diversity indices, principal coordinates analysis (PCoA) with PERMANOVA, and differential abundance testing (DESeq2, FDR < 0.05). Eradication therapy (esomeprazole–bismuth–doxycycline–levofloxacin) achieved success in 54 of 57 H. pylori–positive patients (94.7

BACKGROUND:Autoimmune gastritis (AIG) is a chronic inflammatory condition characterized by the destruction of gastric parietal cells. The invasive nature of diagnostic procedures and risk of confounding factors hinder the development of reliable diagnostic tools for AIG. METHODS:We conducted a systematic search of four databases. After assessing the study quality using the ROBINS-E tool, a meta-analysis was performed using a random-effects model. Meta-regression and sensitivity analyses were conducted to explore the sources of heterogeneity and impact of study bias. RESULTS:The pooled mean difference in total serum ghrelin (pmol/L) between patients with AIG and healthy controls was -65.28 (95% CI: -178.54, 47.97). Subgroup analysis showed that the mean differences in serum ghrelin for mild, moderate, and severe atrophy were -78.85 (95% CI: -165.17, to 7.48), -91.97 (95% CI: -183.11, to -0.84), and -110.67 (95% CI: -204.77, to -16.56), respectively. The sensitivity analysis confirmed that the exclusion of studies with high-risk bias did not significantly alter the results. Meta-regression indicated that BMI contributed substantially to heterogeneity. CONCLUSIONS:Although total serum ghrelin levels were not significantly different between patients with AIG and healthy controls, significantly lower levels were observed in patients with moderate-to-severe gastric atrophy. Given the high heterogeneity and limitations of existing studies, the diagnostic utility of serum ghrelin in AIG warrants further investigation.

Objective To assess the efficacy, safety and compliance with dual, triple and quadruple therapy first-line regimens for Helicobacter pylori eradication.Design A systematic review and network meta-analysis (NMA) reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses NMA guidance.Data sources PubMed, Cochrane Library, ProQuest and Scopus were searched until 12 October 2025.Eligibility criteria Randomised controlled trials (RCTs) published in English that measured the eradication rate, adverse events and compliance rates of dual therapy compared with triple or quadruple therapy for H. pylori first-line treatment.Data extraction and synthesis Data extraction and risk-of-bias assessment were performed by two independent reviewers. The data were analysed and represented as pooled ORs. Heterogeneity was assessed using meta-regression and trim-and-fill analyses.Results Pairwise meta-analysis of 56 RCTs showed that dual therapy had no different eradication rates than triple therapy (intention-to-treat (ITT): OR 0.88, 95% CI 0.60 to 1.29; per-protocol (PP): OR 0.76, 95% CI 0.46 to 1.25). Dual therapy outperformed quadruple therapy (OR 1.20, 95% CI 1.04 to 1.39) with fewer adverse events (OR 0.32, 95% CI 0.28 to 0.38) and higher compliance rates (OR: 1.49, 95% CI 1.26 to 1.76). Based on the NMA, RAC-7 has the highest probability of effective treatment for both ITT (P-score=0.9436) and PP (P-score=0.9545).Conclusion Dual therapy represents a promising first-line option, demonstrating comparable efficacy and adverse event rates with higher compliance, although triple therapy showed the highest probability of being the most effective first-line regimen in the NMA, followed by quadruple therapy. Further studies in non-Asian populations, along with resistance-guided treatment approaches, are needed to refine global eradication strategies.

Background/Objectives: The incidence of gastroesophageal reflux disease (GERD) is increasing worldwide; however, the contribution of gastroduodenal microbiota to GERD phenotypes and symptom severity remains incompletely understood. This study profiled mucosa-associated microbiota from the gastric antrum and duodenum across GERD phenotypes and examined site-specific associations with symptom severity. Methods: Forty individuals with erosive reflux disease (ERD), non-erosive reflux disease (NERD), or an endoscopically normal comparator group underwent 16S rRNA gene sequencing of the V3–V4 region. Community differences were assessed using Bray–Curtis dissimilarity, differential taxa were explored by linear discriminant analysis effect size (LEfSe), and correlations with validated symptom questionnaires (GERD-Q and FSSG) were evaluated. Results: Microbial community structure differed significantly between the antrum and duodenum, with Proteobacteria and Firmicutes predominating at both sites. LEfSe suggested enrichment of Streptococcus, Haemophilus, and Enterobacter in the duodenum, whereas Sphingobium, Acinetobacter, and Aquabacterium were more abundant in the antrum. The genus Helicobacter was relatively enriched in the antrum of ERD samples, whereas Streptococcus-dominant signatures were more prominent in the duodenum. Symptom severity showed stronger associations with duodenal taxa, including Prevotella with epigastric pain, throat clearing, and postnasal drip; Veillonella with early satiety; Neisseria with dyspnea; and Helicobacter with hoarseness, whereas gastric associations were fewer. Conclusions: Overall, gastroduodenal microbiota exhibited site-specific differences across GERD phenotypes. These findings highlight the importance of anatomical context in host–microbe interactions and identify site-specific microbial patterns that warrant validation in larger, phenotypically well-characterized cohorts.

INTRODUCTION:Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders; however, treatment response varies significantly due to Cytochrome P450 2C19 (CYP2C19) genetic polymorphisms that alter individual drug metabolism. Such variation can lead to insufficient acid suppression, resulting in treatment failure or adverse events. Genotype-guided PPI therapy represents an important step toward personalized gastroenterology by optimizing drug efficacy and safety. AREAS COVERED:This review summarizes evidence from clinical trials and meta-analyses examining CYP2C19-mediated differences in the pharmacokinetics and pharmacodynamics of PPIs in both adults and children. Relevant literature was identified primarily through PubMed and clinical guidelines, covering publications from 1989 to 2025. The review focuses on outcomes related to gastroesophageal reflux disease (GERD), Helicobacter pylori eradication, and eosinophilic esophagitis. Current trials indicate that genotype-guided, tailored PPI therapy - through dose adjustment, drug selection, or regimen modification - can improve treatment efficacy and control abdominal symptoms without increasing safety risks or costs. EXPERT OPINION:CYP2C19 genotype-guided therapy constitutes a practical approach to personalized medicine for acid-related disorders. Barriers to widespread implementation include limited test availability, uncertain cost-effectiveness, and insufficient clinician awareness. Future directions include integrating multi-gene pharmacogenomic testing, model-informed dosing, and artificial intelligence-based decision support to advance individualized acid suppression and personalized gastroenterology.

Helicobacter pylori is a gram-negative gastric pathogen associated with several gastric diseases, including cancer. Although prophage sequences are frequently detected in H. pylori genomes, only a limited number of active bacteriophages infecting this species have been analyzed, leaving phage–host interactions poorly understood. Here, we isolated and characterized a novel temperate bacteriophage, 418T1, from the H. pylori strain VN0418. Transmission electron microscopy revealed that 418T1 has a spherical head with a short tail. The phage exhibited a relatively broad host range, forming plaques on 67.6% of the tested strains. Notably, 418T1 remained stable across a wide pH range (pH 3–11), consistent with gastric adaptation. Genomic analysis revealed a 30,690 bp linear double-stranded DNA genome with direct terminal repeats, consistent with a T7-like fixed-end DNA packaging mechanism. Intergenomic similarity analysis classified 418T1 as a novel species within the genus Schmidvirus . Comparative genomics identified two tail protein genes unique to 418T1. Functional characterization revealed that one of these proteins, VN33, specifically binds to H. pylori cells only after cell-surface lipopolysaccharide (LPS) depletion, suggesting that its target is masked by LPS. Our findings expand the current knowledge of H. pylori bacteriophages and provide new insights into phage–host interactions.

The aim of this study was to identify genetic factors responsible for antibiotic resistance in Helicobacter pylori, a bacterium that can cause long-term gastroduodenal disease. The primary resistance of H. pylori to commonly used antibiotics was studied, and high-throughput next-generation sequencing (NGS) was employed to discover genetic determinants of resistance using a reference-based approach. A total of 123 H. pylori strains were cultured and tested for antibiotic susceptibility using an E test. Genotypic analysis was performed using NGS data with ARIBA v2.14.7 and PlasmidSeeker v1.3 for plasmid detection. Statistical correlations between resistant genotypes and phenotypes were evaluated. In addition, a genome-wide association study (GWAS) and linear mixed model were used to identify genetic variants associated with antimicrobial resistance phenotypes while adjusting for covariates such as population structure. Our results showed that 78.2% of the strains were resistant to metronidazole (MTZ), 22.5% to levofloxacin (LVX), 43.5% to clarithromycin (CLR) and 13.7% to amoxicillin (AMX). Resistance to tetracycline was not detected. Multi-drug resistance was detected in 48.8% of the strains. While plasmids were not detected, chromosomal genetic determinants of resistance to CLR, LVX, and AMX were identified, including mutations in 23S rRNA (A2142G and A2143G), gyrA (N87K/Y and D91Y/N/G), and pbp1 A (F366L, S414R, F473V, G595_V596insE, as well as the mutations T558S and T593A/G/P/S). Additionally, missense, frameshift, and nonsense mutations in rdxA were identified as genetic determinants of resistance to MTZ. No genetic determinants associated with tetracycline resistance were detected. A strong correlation was observed between resistance genotypes and phenotypes for CLR, LVX, AMX, and MTZ. In addition, we found that missense, frameshift and nonsense mutations in rdxA were genetic determinants of resistance to MTZ. We did not detect any genetic determinants associated with tetracycline resistance. There was a strong correlation between resistance genotypes and phenotypes for CLR, LVX, AMX, and MTZ. Furthermore, unitig-based GWAS revealed that AMX, LVX, and CLR resistance in H. pylori was mainly caused by chromosomal mutations that affected the targets of these antibiotics (pbp1 A, gyrA, and 23S rRNA, respectively). Our results highlight the need for regular evaluation and alternative therapies in Vietnam, given the high rates of H. pylori resistance to CLR, MTZ, and LVX. Our study also demonstrated the high capacity of NGS to detect genetic resistance determinants and its potential for implementation in local treatment policies.

Background/Aims: Timely detection with highly accurate biomarkers would be helpful in effectively managing colorectal cancer (CRC). We aim to investigate the accuracy of 3 emerging biomarkers—miR-21, miR-24, and miR-145—in detecting synchronous metastases in CRC.Methods: We recruited newly diagnosed CRC patients with extensive investigations to determine cancer staging and metastatic status. The expression levels of miR-21, miR-24, and miR-145 in tumor biopsy were measured using reverse transcription quantitative polymerase chain reaction. Multivariate and receiver operating characteristic analyses were conducted to evaluate the association and performance of these miRNAs in identifying various metastases.Results: Out of the 63 Indonesian patients involved, 37 (58.7%) were diagnosed with localized CRC, whereas the remaining 26 (41.3%) were identified as having metastases: 31.7% liver, 14.3% lung, 3.2% bone, and 4.8% other metastases. There was a significant downregulation of miR-24 expression in metastatic CRC patients compared to those without metastases (0.024 [4.680] vs. 12.900 [42.376], P< 0.01). Overexpression of miR-21 was identified as an independent risk factor of synchronous metastasis (odds ratio [OR], 1.016; 95% confidence interval [CI], 1.003–1.030; P< 0.05), particularly lung (OR, 1.011; 95% CI, 1.002–1.020; P< 0.05) and bone (OR, 1.022; 95% CI, 1.001–1.043; P< 0.05) metastases. No association was found between miR-145 expression and metastatic status. The miR-21/24 ratio accurately identified synchronous metastases irrespective of organ site, with an area under the curve (95% CI) of 0.833 (0.722–0.944) and positive predictive value of 94.4%.Conclusions: Alteration of miR-21 and miR-24 expression levels was associated with a high incidence of synchronous metastases in Indonesian CRC. The miR-21/24 ratio demonstrated significant potential as a biomarker for detecting synchronous metastases in CRC.

Colorectal cancer (CRC) is among the most common cancers worldwide. Due to continued innovations in diagnosis and treatment methods, CRC continues to contribute significantly to cancer-related deaths. Invasive methods, such as endoscopy, are still the most commonly used in CRC diagnostics. However, it is not suitable for countries with limited endoscopy facilities and expertise a major problem in developing countries. Biomarkers nowadays are playing an important role in the identification and therapy of CRC patients. Despite many important technological and methodological advances, some low-invasive biomarkers, including carcinoembryonic antigen, carbohydrate antigen 19-9, tissue polypeptide specific antigen (TPS) and tumor-associated glycoprotein-72, circulating tumor DNA, Insulin-like growth-factor binding protein 2, hematopoietic growth factor and circulating tumor cell. Although various biomarkers have been known, their application has not been widely used in developing countries. Each biomarker has its own characteristics in its use in the management of CRC patients. A combined set of TPS and hematopoietic growth factor has the potential as a diagnostic method for the detection method in early stages in developing countries.

Integrating conjugative elements (ICEs) are mobile genetic elements conferring a wide range of beneficial functions upon their bacterial hosts. Generally, they can be activated from their integrated states to undergo horizontal gene transfer via conjugation. In the case of the human gastric pathogen Helicobacter pylori, a paradigm for extensive genetic diversity, highly efficient natural transformation and recombination processes may superimpose canonical transfer of its two ICEs termed ICEHptfs3 and ICEHptfs4, and thus shape their composition substantially. Here, as a part of the Helicobacter pylori Genome Project (HpGP) initiative, we have analyzed high-quality genome sequences from 1011 clinical strains with respect to their ICE content and variability. We show that both elements are highly prevalent in all H. pylori populations, but have a strong tendency for gene erosion. ICE sequence variations reflect the population structure and show a clear signature of increased horizontal transfer. A detailed map of ICE integration sites revealed local preferences, but also how recombination processes result in hybrid elements or genome rearrangements. Population-specific differences in ICE cargo genes might reflect distinct requirements in the biological functions provided by these mobile elements.

Background/Aims:A genome-wide study identified tumor suppressor P53 (TP53), BRAF, KRAS, COL-3A1, and SOCS-2 as key drivers of tumorigenesis in human colorectal cancers (CRC). We investigated the association between these molecules' expression levels and the progression of clinical stage as well as the occurrence of distant metastasis in CRC. Methods:We recruited adult patients who underwent colonoscopy and had a histologically confirmed diagnosis of CRC. Clinical staging was determined following extensive workups. Immunohistochemistry (IHC) was used to evaluate the expression level of TP53, KRAS, BRAF, COL-3A1 and SOCS-2 in tumor biopsies. Results:The study involved 63 CRC patients, with a distribution across different stages: 1 (1.6%) in stage I, 6 (9.5%) in stage II, 30 (47.6%) in stage III, and 26 (41.3%) in stage IV. The expression level of TP53 gene were inversely correlated with clinical stages (ρ -0.260, p<0.05). Patients with distant metastases had a significantly lower expression of TP53 compared to those without (0.00 [1.00] vs. 1.00 [23.00], p<0.05). Subanalysis of patients with left-sided tumors demonstrates a significantly reduced expression level of TP53 in both lung (0.00 [0.00] vs. 1.00 [5.25], p<0.05) and overall (0.00 [1.00] vs. 1.00 [21.50], p<0.05) metastases. The expression of TP53 was also positively correlated with BRAF, KRAS, COL-3A1, and SOCS-2 (ρ -0.617, p<0.05; ρ -0.272, p<0.05; ρ 0.348, p<0.05; ρ 0.571, p<0.05). Conclusions:TP53 is downregulated in advanced clinical stages and distant metastases, demonstrating its role in aggressive nature of CRC.

BACKGROUND:Variations in Helicobacter pylori infection rates and pathogenicity do not explain the global gastric cancer incidence, indicating that other bacteria may play a role. We investigated the pathogenic factors of H. pylori and their interactions with the gastric microbiome in a population with low gastric cancer but high gastritis rates in Indonesia. METHODS:The study included 66 H. pylori-positive gastric biopsies. DNA was extracted from the bacterial cultures to examine the pathogenic factors of H. pylori. The 16S rRNA V3-V4 region was sequenced using next-generation sequencing. The microbiome analysis concentrated on α-diversity and β-diversity, along with absolute and relative abundances. Correlation analysis and predicted functional inference were conducted using SECOM and PICRUSt2. RESULTS:Helicobacter predominates in H. pylori-infected stomachs, limiting other bacteria. Although α-diversity was non-significant, virulent H. pylori genotypes showed greater microbial diversity, suggesting co-colonization by other taxa. Some taxa were notably abundant across pathogenic subtypes (p < 0.05), such as Veillonella sp. in East Asian-type CagA H. pylori and Klebsiella without babB. The β-diversity results indicated that microbial diversity and abundance varied according to polymorphisms in patients with different H. pylori CagA types, sabA status, homA/B, and iceA subtypes (PERMANOVA test; p < 0.05). H. pylori dominance remains unchanged when atrophy worsens, alongside decreased microbial diversity (p < 0.05 for atrophy stage 0 vs. stages 1 and 2). Microbial correlation analysis revealed that Helicobacter only had a positive linear relationship with Veillonella (SECOM(Pearson2) = 0.51, SECOM(Distance) = 0.60), whereas Streptococcus sp. correlated with several gastric taxa. Predicted functional inference showed several pathways to be depleted when atrophy progresses. CONCLUSION:Various pathogenic factors impact microbial diversity, and bacteria cohabiting in the gastric environment might shape disease outcomes. Additionally, our study uncovers relationships among genera present in the stomach. More research is needed to explore how non-Helicobacter species induce or possibly safeguard against gastric pathologies.