title: The degree of Helicobacter pylori-triggered inflammation is manipulated by preinfection host microbiota.
abstract: Helicobacter pylori infects over 3 billion people worldwide and is the primary risk factor for gastric cancer. Most individuals infected with H. pylori develop only asymptomatic gastritis; however, some develop ulcers or gastric adenocarcinoma. We demonstrate that one previously unappreciated parameter influencing H. pylori disease outcome is variation in the preinfection host microbiota. Utilizing a mouse model, we altered the microbiota by antibiotic treatment and found that these alterations resulted in significantly lowered H. pylori-triggered inflammation. Specifically, antibiotic pretreatment reduced CD4(+) T-helper cells and Ifnγ transcript levels in gastric tissue after H. pylori infection. The bacterial communities in mice with a reduced response to H. pylori displayed many differences from those in untreated mice, including significantly more cluster IV and XIVa Clostridium spp., bacteria known to influence inflammation via regulatory T cell populations. Our findings suggest that microbiota composition, perhaps Clostridium spp., contributes to the variable disease outcome of H. pylori infection by altering the recruitment of CD4(+) T cells to the gastric compartment. Our results suggest that gastric microbiota could be used as a diagnostic tool to determine which patients are at risk for developing severe disease.
authors: Departments of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California, USA.
authors: Annah S
authors: AS
authors: Rolig
authors: Cynthia
authors: C
authors: Cech
authors: Ethan
authors: E
authors: Ahler
authors: J Elliot
authors: JE
authors: Carter
authors: Karen M
authors: KM
authors: Ottemann
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004269:DNA, Bacterial / Q000032:analysis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005756:Gastritis / Q000276:immunology / Q000382:microbiology*; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D007371:Interferon-gamma; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D013270:Stomach / Q000276:immunology / Q000382:microbiology*; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; D007371:Interferon-gamma