Helicobacter pylori-derived extracellular vesicles increased in the gastric juices of gastric adenocarcinoma patients and induced inflammation mainly via specific targeting of gastric epithelial cells

Evidence indicates that Helicobacter pylori is the causative agent of chronic gastritis and perhaps gastric malignancy. Extracellular vesicles (EVs) play an important role in the evolutional process of malignancy due to their genetic material cargo. We aimed to evaluate the clinical significance and biological mechanism of H. pylori EVs on the pathogenesis of gastric malignancy. We performed 16S rDNA-based metagenomic analysis of gastric juices either from endoscopic or surgical patients. From each sample of gastric juices, the bacteria and EVs were isolated. We evaluated the role of H. pylori EVs on the development of gastric inflammation in vitro and in vivo. IVIS spectrum and confocal microscopy were used to examine the distribution of EVs. The metagenomic analyses of the bacteria and EVs showed that Helicobacter and Streptococcus are the two major bacterial genera, and they were significantly increased in abundance in gastric cancer (GC) patients. H. pylori EVs are spherical and contain CagA and VacA. They can induce the production of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β by macrophages, and IL-8 by gastric epithelial cells. Also, EVs induce the expression of interferon gamma, IL-17 and EV-specific immunoglobulin Gs in vivo in mice. EVs were shown to infiltrate and remain in the mouse stomach for an extended time. H. pylori EVs, which are abundant in the gastric juices of GC patients, can induce inflammation and possibly cancer in the stomach, mainly via the production of inflammatory mediators from gastric epithelial cells after selective uptake by the cells. Bacteria-derived vesicles induce inflammation in the stomach, which could explain the link between Helicobacter pylori and stomach cancer. A team from South Korea led by Jae Gyu Kim of Chung-Ang University College of Medicine and Mina Rho of Hanyang University isolated bacteria and the tiny membrane-encapsulated vesicles they produce from the gastric juices of healthy patients and people with stomach diseases, including cancer. They exposed epithelial cells and immune cells from the stomach lining to vesicles derived from H. pylori, a bacterium linked to stomach ulcers and tumors, and observed an increase in the production of inflammatory mediators. The researchers also fed the vesicles to mice and saw that they infiltrated and remained in the animals' stomachs for up to 24 hours, where they triggered a similar inflammatory immune response.