- Helicobacter pylori-mediated gastric pathogenesis is attenuated by treatment of 2-deoxyglucose and metformin
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Hanfu Su , Eun-Jung Bak , Aeryun Kim , Kavinda Tissera , Jeong-Heon Cha , Sungil Jang
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J. Microbiol. 2022;60(8):849-858. Published online June 22, 2022
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DOI: https://doi.org/10.1007/s12275-022-2130-z
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Helicobacter pylori infection causes chronic inflammation
in the stomach, which is linked to the development of gastric
cancer. The anti-inflammatory and anticancer effects of a
glycolysis inhibitor 2-deoxyglucose (2DG) and an antidiabetic
medication metformin (Met) have gotten attention. Using a
Mongolian gerbil animal model, we investigated H. pylorimediated
gastric pathogenesis and how this pathogenesis is
influenced by 2DG and Met. Five-week-old male gerbils were
infected with H. pylori strain 7.13. After 2 weeks of infection,
gerbils were fed 2DG-containing food (0.03% w/w), Met-containing
water (0.5% w/v), or both (Combi) for 2 (short-term)
or 10 weeks (long-term). Gastric pathogenesis and host response
to H. pylori infection were examined by macroscopic
and histopathologic analysis of gerbils’ stomach. As a result,
indicators of gastric pathogenesis by H. pylori infection including
infiltration of polymorphonuclear neutrophils and
lymphocytes, intestinal metaplasia, atrophy, and proliferation
of gastric epithelial cells were attenuated by short-term administration
of 2DG, Met, or Combi. When the infection was
sustained for long-term, gastric pathogenesis in drug-treated
gerbils was equivalent to that in untreated gerbils, with the
exception that the infiltration of neutrophil was reduced by
2DG. Colonization of H. pylori in stomach was unaffected
by both short- and long-term treatments. Our findings demonstrate
that the progression of gastric pathogenesis induced
by H. pylori infection can be attenuated by the shortterm
individual or combinational treatment of 2DG and
Met, implying that 2DG or Met could be considered as a
treatment option for gastric diseases in the early stages of
infection.
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Citations
Citations to this article as recorded by  - Metabolic reprogramming as a key regulator in Helicobacter pylori-infected gastric cancer
Ruofan Cao, Feifei Zhou, Cuiyu Zhu, Hongwei Xu
Gastric Cancer.2026; 29(1): 1. CrossRef - Chemoprevention strategies for precancerous gastric lesions beyond Helicobacter pylori eradication
Tai Zhang, Xudong Tang
QJM: An International Journal of Medicine.2025; 118(6): 385. CrossRef - Antibacterial and Immunoregulatory Effects of Metformin against Helicobacter pylori Infection in Rat Model
Hassan Valadbeigi, Saeed Khoshnood, Babak Negahdari, Mohd Azmuddin Abdullah, Mohammad Hossein Haddadi, Abhimanyu Abhimanyu
BioMed Research International.2023;[Epub] CrossRef - Effect of Metformin on the Prognosis of Gastric Cancer Patients with Type 2 Diabetes Mellitus: A Meta-Analysis Based on Retrospective Cohort Studies
Lingna Li, Jianing Huang, Tongmin Huang, Jie Yao, Yeyuan Zhang, Meiling Chen, Haojie Shentu, Haiying Lou, Flavia Prodam
International Journal of Endocrinology.2023; 2023: 1. CrossRef
- Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA
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Kavinda Tissera , Myeong-A Kim , Jing Lai , Sacheera Angulmaduwa , Aeryun Kim , D. Scott Merrell , Ji-Hye Kim , Hanfu Su , Jeong-Heon Cha
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J. Microbiol. 2022;60(2):207-214. Published online November 10, 2021
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DOI: https://doi.org/10.1007/s12275-022-1483-7
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1,076
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The polymorphic bacterial oncoprotein, CagA shows geography-
dependent variation in the C-terminal Glu-Pro-Ile-
Tyr-Ala (EPIYA) motifs; East-Asian H. pylori isolates carry
the ABD type while Western isolates carry the ABC type. In
Western isolates, the EPIYA-C motif is sometimes found in
multi-copy and this genotype is associated with disease severity.
Interestingly, a small number of East-Asian H. pylori
isolates have been found to carry Western ABC-type CagA.
To gain a better understanding of these unusual isolates, the
genomes of four Korean H. pylori clinical isolates carrying
ABC-type CagA were sequenced via third generation (Pac-
Bio SMRT) sequencing technology. The obtained data were
utilized for phylogenetic analysis as well as comparison of
additional virulence factors that are known to show geographic-
dependent polymorphisms. Three of four isolates indeed
belonged to the hpEastAsia group and showed typical East-
Asian polymorphism in virulence factors such as homA/B/C,
babA/B/C, and oipA. One isolate grouped to HpAfrica and
showed typical Western polymorphism of virulence factors
such as cagA, homA/B/C, and oipA. To understand the occurrence
of the multi-copy EPIYA-C motif genotype in an East-
Asian H. pylori background, the Korean clinical isolate, K154
was analyzed; this strain belonged to hpEastAsia but encoded
CagA EPIYA-ABCCCC. Based on DNA sequence homology
within the CagA multimerization (CM) sequence that flanked
the EPIYA-C motifs, we predicted that the number of C motifs
might change via homologous recombination. To test this
hypothesis, K154 was cultured for one generation and 287
single colonies were analyzed for the number of EPIYA-C
motifs using PCR-based screening and DNA sequencing verification.
Three out of 284 (1%) single colony isolates showed
changes in the number of EPIYA-C motifs in vitro; one isolate
increased to five EPIYA-C motifs, one decreased to three
EPIYA-C motifs, and one completely deleted the EPIYA-C
motifs. The capacity for dynamic changes in the number of
EPIYA-C repeats of CagA may play a role in generating important
intraspecies diversity in East-Asian H. pylori.
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Citations
Citations to this article as recorded by - Helicobacter pylori’s Seven-housekeeping Gene and CagA EPIYA Motif Patterns Linking to Gastrointestinal Diseases
Nattamon Narkwichearn, Phataraporn Khumphai, Sasiporn Tongman, K.-S. Cheng
BIO Web of Conferences.2025; 163: 01002. CrossRef - Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer
Zhijing Xue, Weijia Li, Hailing Ding, Fengyan Pei, Jianzhong Zhang, Yanan Gong, Ruyue Fan, Fang Wang, Youjun Wang, Qing Chen, Yanran Li, Xinyu Yang, Yan Zheng, Guohai Su, Saeid Ghavami
PLOS ONE.2024; 19(9): e0309844. CrossRef - Amino acid deletions at positions 893 and 894 of cytotoxin-associated gene A protein affect Helicobacter pylori gastric epithelial cell interactions
Zhi-Jing Xue, Ya-Nan Gong, Li-Hua He, Lu Sun, Yuan-Hai You, Dong-Jie Fan, Mao-Jun Zhang, Xiao-Mei Yan, Jian-Zhong Zhang
World Journal of Gastroenterology.2024; 30(41): 4449. CrossRef - Characteristics of different types of Helicobacter pylori: New evidence from non-amplified white light endoscopy
Weidong Liu, Wenjie Kong, Wenjia Hui, Chun Wang, Qi Jiang, Hong Shi, Feng Gao
Frontiers in Microbiology.2023;[Epub] CrossRef
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