{
  "abstract": "Stomach colonization by Helicobacter pylori (H. pylori) has been reported in over 50% of the global human population. Although H. pylori is the main etiological factor influencing the development of gastric cancer (GC), the mechanisms through which H. pylori impairs host autophagy and facilitates malignant transformation of host cells are unknown. This review advances the central hypothesis of a stage-dependent, dual role of autophagy during the natural H. pylori infection course. In acute H. pylori infection, autophagy acts as a crucial tumor-suppressive mechanism: it degrades internalized bacteria and the translocated oncoprotein CagA, removes damaged mitochondria, mitigates reactive oxygen species generation, and restricts inflammatory signaling, thus preserving epithelial homeostasis and genomic integrity. However, during chronic H. pylori infection, the pathogen disrupts this balance by impairing autophagic flux, transforming the pathway into a pro-tumorigenic phenotype that promotes SQSTM1/p62 accumulation, sustained NF-κB and STAT3 activation, genomic instability, and epithelial-mesenchymal transition. Here, we dissect the mechanistic crosstalk through which the key virulence factors—VacA, CagA, HP0175, and HpGGT—differentially modulate autophagosome biogenesis and lysosomal degradation. Moreover, we integrate the role of host genetic determinants (ATG16L1, NOD2, and IRGM) that impact the outcome of H. pylori infection. We further synthesize the networks of H. pylori-responsive microRNAs that fine-tune autophagy and elucidate their emerging significance as diagnostic and prognostic biomarkers. Furthermore, as potential GC interventions, we critically evaluate treatments that modulate autophagy, including inducers and inhibitors of autophagy. We also assess a persistent and often neglected source of evidence with conflicting perspectives: the inability to differentiate between actual autophagy induction and blocked autophagic flux; moreover, we describe the methodological rigor required to effectively address this issue. In this review, we reconcile these controversies within a single stage-dependent framework to provide a mechanistic and translational roadmap to target the autophagy-H. pylori axis for preventing and treating GC.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Review",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Fuping Li"
    },
    {
      "name": "Bixian Luo"
    },
    {
      "name": "Jun He"
    },
    {
      "name": "Chengyu Hu"
    },
    {
      "name": "Weixun Xie"
    },
    {
      "name": "Hongming Liu"
    },
    {
      "name": "Zelai Wu"
    },
    {
      "name": "Weihua Gong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/971qgvknft4xv.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.2000318",
  "fulltext_url": null,
  "id": "971qgvknft4xv",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.2000318",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/971qgvknft4xv.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:15Z",
      "native_id": "10.3389/fphar.2026.2000318",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.2000318"
    },
    {
      "first_seen": "2026-11-05T12:21:25Z",
      "native_id": "10.3389/fphar.2026.2000318",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.2000318/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Beyond the “double-edged sword”: a stage-resolved framework for autophagy in Helicobacter pylori-associated gastric cancer",
  "title_text": "Beyond the “double-edged sword”: a stage-resolved framework for autophagy in Helicobacter pylori-associated gastric cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T00:21:24Z",
  "url": "https://research.draconitic.com/paper/971qgvknft4xv",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}