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    IDDF2023-ABS-0237 Characteristics of helicobacter pylori from mongolia where burdening high incidence of gastric cancer
    (2023-06-01) ; ;
    Khasag Oyuntsetseg
    ;
    Yoshio Yamaoka
    ;
    Vo Phuoc Tuan
    Background Globally Mongolia is the top country in the incidence of gastric cancer followed by Japan and Korea which are East Asian countries. Helicobacter pylori (H. pylori) infection possessing East-Asian-type CagA is more associated with gastric carcinogenesis than Western-type CagA. The prevalence of H. pylori is around 70% in Mongolia; however, the previous study reported Mongolians infected with H. pylori possessing Western-type CagA. Therefore, we aimed to characterize Mongolian H. pylori infection based on a whole genome sequencing method. Methods Totally 130 strains are sequenced from Mongolian H. pylori isolates (20 gastric cancer and 110 non-cancer cases) and 401 data from 38 countries H. pylori whole genome data were extracted for the FineStructure analysis. The complete CagA gene and 7 housekeeping genes were extracted for constructing a phylogenetic tree. Results Based on whole genomic FineStructure analysis we found new H. pylori population named as HpMongolia among Mongolian gastric cancer and non-gastric cancer cases which are separately clustered among published global H. pylori populations (IDDF2023-ABS-0237-Figure 1. FineStructure analysis for H.pylori population). Complete CagA gene sequencing data showed that HpMongolia possessed with J-Western type cagA and it was the highest distribution of J-Western cagA positive H. pylori strains identified in Mongolia (67.7%) followed by Canada, North America (10%), and Okinawa, Japan (5.9%) among the published population (IDDF2023-ABS-0237-Figure 2. Global H.pylori phylogenetic tree based on 7-housekeeping genes). The phylogenetic tree constructed based on 7 housekeeping genes result showed the closest H. pylori population with HpMongolia is the HpAmerind which is isolated from native American people (IDDF2023-ABS-0237-Figure 3. H.pylori CagA genotyping map). Conclusions Mongolians provide new H. pylori population is named as HpMongolia which contains most of the cases Japanese-Western type cagA both for cancer and non-cancer cases. Therefore Japanese-Western type cagA might have advantageous for human migration study markers and further clinical implications.
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    IDDF2022-ABS-0128 A novel pathogen enterococcus hirae induced dysbiosis in the stomach and the genomic instability to promote gastric cancer
    (2022-09-01) ; ;
    Junko K. Akada
    ;
    Takashi Matsumoto
    ;
    Ricky Indra Alfaray
    Background Previous our microbiome analysis indicates that Enterococcus sp. predominance of microbial composition has been determined in patients with gastric cancer (GC) by 16S rRNA metagenomic analysis. We aimed to determine whether this bacterium could promote the emergence and progression of GC. Methods The effects of E. hirae and Helicobacter pylori (clinical strain Mon-Ke2 as control) were assessed in a gastric epithelial cell line (AGS cells). The cell toxicity of AGS cells is identified by lactate dehydrogenase levels. The DNA double-strand breaks (DSBs) were assessed by gamma-H2AX expressions using immunoblotting; and single-cell gel electrophoresis (SCGE). AGS cells were analyzed for the rapid oxygen species (ROS) expressions response after E. hirae and H. pylori infections. Results E. hirae was successfully isolated from the gastric mucosal specimen of a GC patient for the first time. The whole-genome sequence of E. hirae was confirmed by next-generation sequencing. E. hirae-infected AGS cells showed abnormal morphological changes. Infections of E. hirae and H. pylori significantly induced cell death and expression of gH2AX in AGS cells. Besides, the expression of gH2AX and DSBs was confirmed by SCGE comet formation. Interestingly, co-infection of H. pylori and E. hirae had a synergistic effect on the severity of DSBs. E. hirae could induce intranucleus and mitochondrial ROS in AGS cells same as H. pylori. We investigated whether only live E. hirae, or its released factor(s) can cause DNA damage. Supernatant from AGS cells infected with E. hirae could induce the gH2AX, whereas H. pylori required cell adhesion to induce gH2AX. The complete genome of E. hirae totally contained 2570 genes and 10 known virulence factor genes (e.g., Enterococcus pore-forming toxin). Conclusions E. hirae-related dysbiosis in the stomach might increase the risk for GC, resulting in gained the genomic instability of gastric cells, as well as H. pylori infection. Further research investigating the impacts of this pathogen on the human host using the gastric organoid model is needed since several studies have shown that other species of Enterococcus induce cancer-promoting events resulting in DNA damage in gastric/colonic mucosa, and hepatic cells.
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    1257 ENTEROCCUS HIRAE ATTENUATES CHEMOKINE AND INDUCES DNA DAMAGE IN GASTRIC EPITHELIAL CELLS
    (Elsevier BV, 2023-05-01) ;
    Boldbaatar Gantuya
    ;
    Ricky Indra Alfaray
    ;
    Junko K. Akada
    ;
    Takashi Matsumoto