Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510182, P. R. China.
Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea.
J Microbiol. 2022 Aug;60(8):849-858. doi: 10.1007/s12275-022-2130-z. Epub 2022 Jun 22.
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. pylori-mediated 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 short-term 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.
幽门螺杆菌感染会导致胃部慢性炎症，进而增加胃癌的发病风险。2-脱氧葡萄糖（2DG）作为一种糖酵解抑制剂和抗糖尿病药物二甲双胍（Met）具有抗炎和抗癌作用，引起了人们的关注。本研究使用蒙古沙土鼠动物模型，探究了幽门螺杆菌介导的胃部发病机制，以及 2DG 和 Met 对该发病机制的影响。5 周龄雄性沙土鼠感染幽门螺杆菌菌株 7.13。感染 2 周后，沙土鼠喂食含 2DG 的食物（0.03%w/w）、含 Met 的水（0.5%w/v）或两者的混合物（Combi）2 周（短期）或 10 周（长期）。通过对沙土鼠胃部的大体和组织病理学分析，研究了幽门螺杆菌感染导致的胃部发病机制及宿主对感染的反应。结果显示，短期给予 2DG、Met 或 Combi 可减轻幽门螺杆菌感染导致的多种胃部发病机制的指标，包括多形核中性粒细胞和淋巴细胞浸润、肠上皮化生、萎缩和胃上皮细胞增殖。当感染持续时间较长时，药物治疗组沙土鼠的胃部发病机制与未治疗组沙土鼠相当，只是 2DG 治疗组中性粒细胞浸润减少。短期和长期治疗均不影响幽门螺杆菌在胃内的定植。综上，我们的研究结果表明，2DG 和 Met 的短期单独或联合治疗可减轻幽门螺杆菌感染引起的胃部发病机制进展，这意味着 2DG 或 Met 可作为感染早期胃部疾病的治疗选择。
