The interaction between autophagy, Helicobacter pylori, and gut microbiota in gastric carcinogenesis

Autophagy orchestrates cell homeostasis and cellular stress signaling, and implements a dichotomous function in different stages of cancer development. The stress signals in the tumor microenvironment differentially regulate the autophagy pathway, subsequently modulating tumor immunity, progression, and metastasis. Autophagy manipulation represents a prominent strategy for intracellular Helicobacter pylori replication and timely release of oncoproteins. Autophagy signaling network widely contributes to gut homeostasis persistence, gut ecology architecture, and antimicrobial protection. H. pylori-induced dysbiosis of gut microbiota and metabolic profiles can provide an infrastructure for gastric cancer development and progression. Although not confirmed, evidence suggests the potential for H. pylori to modify the gut microbiota through autophagy modulation. Chronic infection with Helicobacter pylori is the primary risk factor for the development of gastric cancer. Hindering our ability to comprehend the precise role of autophagy during H. pylori infection is the complexity of context-dependent autophagy signaling pathways. Recent and ongoing progress in understanding H. pylori virulence allows new frontiers of research for the crosstalk between autophagy and H. pylori. Novel approaches toward discovering autophagy signaling networks have further revealed their critical influence on the structure of gut microbiota and the metabolome. Here we intend to present a holistic view of the perplexing role of autophagy in H. pylori pathogenesis and carcinogenesis. We also discuss the intermediate role of autophagy in H. pylori-mediated modification of gut inflammatory responses and microbiota structure. Chronic infection with Helicobacter pylori is the primary risk factor for the development of gastric cancer. Hindering our ability to comprehend the precise role of autophagy during H. pylori infection is the complexity of context-dependent autophagy signaling pathways. Recent and ongoing progress in understanding H. pylori virulence allows new frontiers of research for the crosstalk between autophagy and H. pylori. Novel approaches toward discovering autophagy signaling networks have further revealed their critical influence on the structure of gut microbiota and the metabolome. Here we intend to present a holistic view of the perplexing role of autophagy in H. pylori pathogenesis and carcinogenesis. We also discuss the intermediate role of autophagy in H. pylori-mediated modification of gut inflammatory responses and microbiota structure. a type of regulated cell death that involves the action of caspases. autophagy-mediated induction of apoptosis or the activation of a distinct autophagy-dependent mechanism that leads to cell death. processes involved in the lysosomal degradation and recycling of cytoplasmic components. these genes encode the components of the macroautophagy machinery. The acronym ‘ATG’ indicates 'autophagy related', but some components such as BECN1 are also considered to be part of this group. a component of the class III PtdIns3K that generates phosphatidylinositol-3-phosphate; this lipid is required for autophagy. a 40-kb genomic DNA segment that encodes the T4SS; these genes are the most well-recognized virulence determinants of H. pylori. a small protein secreted by different types of cells including immune and endothelial cells that interact with cell surface receptors to trigger various responses within the target cells. aberrant compositional and functional modification of the microbiota that disturbs the indigenous microbial ecosystem. a cytoplasmic multiprotein complex that detects pathogenic microorganisms and danger signals in the host cells. a type of selective autophagy that degrades dysfunctional or damaged mitochondria. MTOR regulates cell growth and is the primary negative regulator of macroautophagy. the initial sequestering compartment of macroautophagy; the phagophore surrounds cargo and matures into a double-membrane autophagosome. a lytic type of cell death triggered by inflammasome stimulation and consequent inflammatory caspase activation. chemical byproducts derived from oxygen including peroxides, superoxide, and hydroxy radical; these highly reactive species can damage cellular components. the dynamic surrounding microenvironment of tumor cells that is spatially and temporally modified in response to environmental factors and antitumor therapeutics. a bacterial protein complex located in the plasma membrane that transports protein and DNA into the extracellular space. a selective form of macroautophagy involving the elimination of intracellular microbes.