Journal Article

Crosstalk between Helicobacter pylori and Gastric Epithelial Cells Is Impaired by Docosahexaenoic Acid

Matos, António A., Correia, Marta, El Ghachi, Meriem, Lenormand, Pascal, Seruca, Raquel, De Reuse, Hilde, Machado, Jose Carlos, Touati, Eliette, Bonis, Mathilde, Michel, Valérie, Figueiredo, Ceu, Osório, Hugo, Boneca, Ivo G.

2013

Overview

H. pylori colonizes half of the world's population leading to gastritis, ulcers and gastric cancer. H. pylori strains resistant to antibiotics are increasing which raises the need for alternative therapeutic approaches. Docosahexaenoic acid (DHA) has been shown to decrease H. pylori growth and its associated-inflammation through mechanisms poorly characterized. We aimed to explore DHA action on H. pylori-mediated inflammation and adhesion to gastric epithelial cells (AGS) and also to identify bacterial structures affected by DHA. H. pylori growth and metabolism was assessed in liquid cultures. Bacterial adhesion to AGS cells was visualized by transmission electron microscopy and quantified by an Enzyme Linked Immunosorbent Assay. Inflammatory proteins were assessed by immunoblotting in infected AGS cells, previously treated with DHA. Bacterial total and outer membrane protein composition was analyzed by 2-dimensional gel electrophoresis. Concentrations of 100 µM of DHA decreased H. pylori growth, whereas concentrations higher than 250 µM irreversibly inhibited bacteria survival. DHA reduced ATP production and adhesion to AGS cells. AGS cells infected with DHA pre-treated H. pylori showed a 3-fold reduction in Interleukin-8 (IL-8) production and a decrease of COX2 and iNOS. 2D electrophoresis analysis revealed that DHA changed the expression of H. pylori outer membrane proteins associated with stress response and metabolism and modified bacterial lipopolysaccharide phenotype. As conclusions our results show that DHA anti-H. pylori effects are associated with changes of bacteria morphology and metabolism, and with alteration of outer membrane proteins composition, that ultimately reduce the adhesion of bacteria and the burden of H. pylori-related inflammation.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Adhesion / Adhesion tests / Analysis / Angiogenesis / Anti-Inflammatory Agents / Anti-Inflammatory Agents - pharmacology / Anti-Inflammatory Agents - therapeutic use / Antibiotics / Antiulcer agents / Apoptosis / Bacteria / Bacterial Adhesion / Bacterial Adhesion - drug effects / Bacterial Outer Membrane Proteins / Bacterial Outer Membrane Proteins - metabolism / Biology / Cancer / Cell adhesion & migration / Cell cycle / Cell survival / Cell Wall / Cell Wall - drug effects / Cell Wall - metabolism / Cellular Biology / Crosstalk / Cyclooxygenase-2 / Docosahexaenoic acid / Docosahexaenoic Acids / Docosahexaenoic Acids - pharmacology / Docosahexaenoic Acids - therapeutic use / Electron microscopy / Electrophoresis / Enzyme-linked immunosorbent assay / Epithelial Cells / Epithelial Cells - drug effects / Epithelial Cells - microbiology / Fatty acids / Gastric cancer / Gastritis / Gel electrophoresis / Gene expression / Health aspects / Helicobacter pylori / Helicobacter pylori - cytology / Helicobacter pylori - drug effects / Helicobacter pylori - growth & development / Helicobacter pylori - physiology / Immunoblotting / Immunology / Infections / Inflammation / Inflammation - drug therapy / Inflammation - microbiology / Interleukin / Interleukin 8 / Life Sciences / Lipopolysaccharides / Medicine / Membrane proteins / Metabolism / Microbiology and Parasitology / Nitric-oxide synthase / Omega 3 fatty acids / Outer membrane proteins / Pathology / Phase transitions / Physiological aspects / Protein composition / Proteins / Stomach / Stomach - cytology / Stomach cancer / Transmission electron microscopy / Two dimensional analysis / Ulcers / Unsaturated fatty acids