RT Journal Article SR Electronic T1 Sustained Helicobacter pylori infection accelerates gastric dysplasia in a mouse model JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202000967 DO 10.26508/lsa.202000967 VO 4 IS 2 A1 Valerie P O’Brien A1 Amanda L Koehne A1 Julien Dubrulle A1 Armando E Rodriguez A1 Christina K Leverich A1 V Paul Kong A1 Jean S Campbell A1 Robert H Pierce A1 James R Goldenring A1 Eunyoung Choi A1 Nina R Salama YR 2021 UL https://www.life-science-alliance.org/content/4/2/e202000967.abstract AB More than 80% of gastric cancer is attributable to stomach infection with Helicobacter pylori (Hp). Gastric preneoplastic progression involves sequential tissue changes, including loss of parietal cells, metaplasia and dysplasia. In transgenic mice, active KRAS expression recapitulates these tissue changes in the absence of Hp infection. This model provides an experimental system to investigate additional roles of Hp in preneoplastic progression, beyond its known role in initiating inflammation. Tissue histology, gene expression, the immune cell repertoire, and metaplasia and dysplasia marker expression were assessed in KRAS+ mice +/−Hp infection. Hp+/KRAS+ mice had severe T-cell infiltration and altered macrophage polarization; a different trajectory of metaplasia; more dysplastic glands; and greater proliferation of metaplastic and dysplastic glands. Eradication of Hp with antibiotics, even after onset of metaplasia, prevented or reversed these tissue phenotypes. These results suggest that gastric preneoplastic progression differs between Hp+ and Hp− cases, and that sustained Hp infection can promote the later stages of gastric preneoplastic progression.