Association of gastric microbiota with gastric cancer in patients infected with helicobacter pylori

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dc.authorid0000-0003-1072-3846
dc.authorid0000-0003-3093-9070
dc.authorid0000-0001-9670-2426
dc.authorid0000-0001-8056-4428
dc.authorid0000-0002-0812-1128
dc.authorid0000-0002-0050-9099
dc.authorid0000-0002-0596-1551
dc.authorid0000-0002-6993-0383
dc.authorid0000-0002-2205-5120
dc.contributor.authorKocazeybek, Bekir
dc.contributor.authorBal, Kadir
dc.contributor.authorAkkuş, Seher
dc.contributor.authorDemirci, Mehmet
dc.contributor.authorKurt, Enes Ali
dc.contributor.authorGareayaghi, Nesrin
dc.contributor.authorDemiryas, Süleyman
dc.contributor.authorÖzbey, Doğukan
dc.contributor.authorAkçin, Rüveyda
dc.contributor.authorBahar Tokman, Hrisi
dc.date.accessioned2026-10-09T09:01:49Z
dc.date.available2026-10-09T09:01:49Z
dc.date.issued2026
dc.departmentFakülteler, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Mikrobiyoloji Ana Bilim Dalı
dc.description.abstractBackground: The association between Helicobacter pylori and the resident gastric microbiota plays a critical role in gastric carcinogenesis; however, the specific microbial alterations accompanying the transition from chronic inflammation to malignancy remain to be fully elucidated. This study aimed to characterize the distinct bacterial signatures associated with gastric cancer (GC) and non-ulcer dyspepsia (NUD) within a Turkish cohort, evaluating these structural shifts in the context of the “hit-and-run” hypothesis. Methods: Genomic DNA was isolated from 158 gastric biopsy specimens obtained from 96 individuals stratified into four homogeneous groups based on clinical H. pylori status and histopathological presentation: H. pylori-positive GC (Hp+GC, n = 37), H. pylori-negative GC (Hp-GC, n = 25), H. pylori-positive NUD (Hp+NUD, n = 17), and H. pylori-negative NUD (Hp-NUD, n = 17). Next-generation amplicon sequencing targeting the V3–V4 hypervariable regions of the 16S rRNA gene was executed, followed by strict quality filtering via the DADA2 pipeline and taxonomic classification against the SILVA database. Results: Alpha diversity analysis demonstrated a significant reduction in microbial richness and evenness within the Hp+GC group compared with all other cohorts (FDR-adjusted q < 0.001). Beta diversity metrics revealed distinct ecological trajectories, with the overall microbial community structure of the Hp+GC group diverging sharply from non-malignant controls. Taxonomic profiling unveiled a profound dysbiotic shift in the Hp+GC microenvironment, characterized by a massive depletion of the Firmicutes phylum and a concomitant overrepresentation of Proteobacteria (66.56%). While the Helicobacter genus predominated in the non-malignant Hp+NUD group, its relative abundance declined to negligible levels (<0.01%) in biopsy samples of gastric cancer patients, despite clinical positivity. This malignant niche was instead robustly invaded by potentially pathogenic bacteria belonging to the Enterobacteriaceae family, showing highly significant enrichment of Morganella (11.14% mean relative abundance; FDR-adjusted q < 0.001), Providencia (3.43%; FDR-adjusted q < 0.001), and Klebsiella (2.03%; FDR-adjusted q < 0.001). Conclusions: These findings support the “hit-and-run” model, indicating that H. pylori acts as an initiator of carcinogenesis but is progressively outcompeted by an aggressive, nitrate-reducing, and pro-inflammatory Enterobacteriaceae-dominated dysbiotic bacterial community as mucosal atrophy and hypochlorhydria neutralize the typical acidic gastric barrier.
dc.description.sponsorshipThe current study was supported by the Turkish Gastroenterology Society, [No. 17.11.2019/19–1]. Bu çalışma, Türk Gastroenteroloji Derneği tarafından desteklenmiştir [No. 17.11.2019/19–1].
dc.identifier.citationKocazeybek, B., Bal, K., Akkuş, S., Demirci, M., Kurt, E. A., Gareayaghi, N., Demiryas, S., Özbey, D., Akçin, R., & Bahar Tokman, H. (2026). Association of gastric microbiota with gastric cancer in patients infected with helicobacter pylori. Pathogens, 15(10), pp. 1-18. https://doi.org/10.3390/pathogens15101051
dc.identifier.doi10.3390/pathogens15101051
dc.identifier.endpage18
dc.identifier.issn2076-0817
dc.identifier.issue10
dc.identifier.scopusqualityQ1
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.3390/pathogens15101051
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1663
dc.identifier.volume15
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorAkçin, Rüveyda
dc.institutionauthorid0000-0002-6993-0383
dc.language.isoen
dc.publisherMDPI Publishing
dc.relation.ispartofPathogens
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHelicobacter Pylori
dc.subjectGastric Microbiota
dc.subjectEnterobacteriaceae
dc.subjectGastric Cancer
dc.subject16S rRNA Sequencing
dc.titleAssociation of gastric microbiota with gastric cancer in patients infected with helicobacter pylori
dc.typeArticle
dspace.entity.typePublication

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