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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. [ABSTRACT FROM AUTHOR]

Helicobacter pylori as a class I carcinogen is correlated with a variety of severe gastroduodenal diseases; therefore, H. pylori eradication has become a priority to prevent gastric carcinogenesis. However, due to the emergence and spread of multidrug and single drug resistance mechanisms in H. pylori, as well as serious side effects of currently used antibiotic interventions, achieving successful H. pylori eradication has become exceedingly difficult. Recent studies expressed the intention of seeking novel strategies to improve H. pylori management and reduce the risk of H. pylori-associated intestinal and extragastrointestinal disorders. For which, vitamin supplementation has been demonstrated in many studies to have a tight interaction with H. pylori infection, either directly through the regulation of the host inflammatory pathways or indirectly by promoting the host immune response. On the other hand, H. pylori infection is reported to result in micronutrient malabsorption or deficiency. Furthermore, serum levels of particular micronutrients, especially vitamin D, are inversely correlated to the risk of H. pylori infection and eradication failure. Accordingly, vitamin supplementation might increase the efficiency of H. pylori eradication and reduce the risk of drug-related adverse effects. Therefore, this review aims at highlighting the regulatory role of micronutrients in H. pylori-induced host immune response and their potential capacity, as intrinsic antioxidants, for reducing oxidative stress and inflammation. We also discuss the uncovered mechanisms underlying the molecular and serological interactions between micronutrients and H. pylori infection to present a perspective for innovative in vitro investigations, as well as novel clinical implications. [ABSTRACT FROM AUTHOR]

Helicobacter pylori outer membrane vesicles (OMVs) are nano-sized structures, which have been recently suggested to play a crucial role in H. pylori pathogenesis. There are growing evidence indicating the relationship of H. pylori infection with extra-gastroduodenal diseases, especially liver-related disorders. This study was aimed to investigate the effects of H. pylori -derived OMVs on autophagy in hepatic stellate cells (HSCs). A selection of five clinical strains of H. pylori with different virulence genotypes were included. The OMVs were isolated by ultracentrifugation and characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The protein concentration of OMVs was measured by BCA assay. MTT assay was used to determine the viability of LX-2 cells (human HSCs) treated with OMVs. The expression level of MTOR, AKT, PI3K, BECN1, ATG16 and LC3B genes was assessed in OMVs-treated LX-2 cells using quantitative real-time PCR. Moreover, immunocytochemistry was performed to evaluate the protein expression of MTOR and LC3B autophagy markers. H. pylori strains produced round shape nano-vesicles ranging from 50 to 500 nm. Treatment of HSCs with H. pylori -derived OMVs at concentration of 10 μg/mL for 24 h significantly elevated the expression of autophagy inhibitory markers (PI3K, AKT, and MTOR) and suppressed the mRNA expression level of autophagy core proteins (BECN1, ATG16 and LC3B). Immunocytochemistry also presented a substantial reduction in the concentration of LC3B autophagy core protein, and a marked elevation in the amount of MTOR autophagy inhibitory protein. This study revealed that H. pylori -derived OMVs could potentially suppress autophagy flux in HSCs as a novel mechanism for H. pylori- mediated liver autophagy impairment and liver disease development. Further studies are required to elucidate the exact role of OMV-carried contents in liver autophagy, and liver-associated disorders. • H. pylori -derived OMVs suppressed the autophagy process in human HSCs. • H. pylori -mediated impairment of liver autophagy could lead to hepatic disorders. • OMV-carried H. pylori virulence factors might contribute to liver autophagy suppression. [ABSTRACT FROM AUTHOR]