Loss of Corpus-Specific Lipids in Helicobacter pylori-Induced Atrophic Gastritis.

Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101674533 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2379-5042 (Electronic) Linking ISSN: 23795042 NLM ISO Abbreviation: mSphere Subsets: MEDLINE

Original Publication: Washington, DC : American Society for Microbiology, [2015]-

Helicobacter pylori*; Gastritis, Atrophic/*microbiology ; Helicobacter Infections/*pathology ; Stomach Neoplasms/*etiology; Animals ; Disease Models, Animal ; Gastritis, Atrophic/pathology ; Gerbillinae ; Lipid Metabolism ; Male ; Stomach/pathology

Helicobacter pylori colonization of the stomach is a strong risk factor for the development of stomach cancer and peptic ulcer disease. In this study, we tested the hypothesis that H. pylori infection triggers alterations in gastric lipid composition. Mongolian gerbils were experimentally infected with H. pylori for 3 months. Conventional histologic staining revealed mucosal inflammation in stomachs from the H. pylori-infected animals but not in stomachs from uninfected control animals. Atrophic gastritis (a premalignant condition characterized by loss of corpus-specific parietal and chief cells), gastric mucosal hyperplasia, dysplasia, and/or gastric cancer were detected in stomachs from several infected animals. We then used imaging mass spectrometry to analyze the relative abundance and spatial distribution of gastric lipids. We detected ions corresponding to 36 distinct lipids that were differentially abundant when comparing gastric tissues from H. pylori-infected animals with tissues from uninfected animals. Liquid chromatography-tandem mass spectrometry analysis of lipid extracts from homogenized gastric tissues provided additional supportive evidence for the identification of several differentially abundant lipids. Sixteen of the differentially abundant lipids were localized mainly to the gastric corpus in stomachs from uninfected animals and were markedly reduced in abundance in stomachs from H. pylori-infected animals with severe disease (atrophic gastritis and dysplasia or gastric cancer). These findings indicate that H. pylori infection can lead to alterations in gastric lipid composition and constitute a new approach for identifying biomarkers of gastric atrophy and premalignant changes. IMPORTANCE H. pylori colonization of the stomach triggers a cascade of gastric alterations that can potentially culminate in stomach cancer. The molecular alterations that occur in gastric tissue prior to development of stomach cancer are not well understood. We demonstrate here that H. pylori-induced premalignant changes in the stomach are accompanied by extensive alterations in gastric lipid composition. These alterations are predicted to have important functional consequences relevant to H. pylori-host interactions and the pathogenesis of gastric cancer.

T32 AI007474 United States AI NIAID NIH HHS; P41 GM103391 United States GM NIGMS NIH HHS; P30 DK058404 United States DK NIDDK NIH HHS; S10 OD023514 United States OD NIH HHS; T32 AI007281 United States AI NIAID NIH HHS; P01 CA116087 United States CA NCI NIH HHS; R01 AI118932 United States AI NIAID NIH HHS; P30 CA068485 United States CA NCI NIH HHS; R01 AI039657 United States AI NIAID NIH HHS; I01 BX004447 United States BX BLRD VA

Keywords: atrophic gastritis; chief cells; gastric cancer; imaging mass spectrometry; parietal cells

Date Created: 20211124 Date Completed: 20220211 Latest Revision: 20220429

20240829

PMC8612251

10.1128/mSphere.00826-21

34817238