title: Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils.
abstract: BACKGROUND
  Gastrointestinal (GI) inflammation in mice and men are frequently accompanied by distinct changes of the GI microbiota composition at sites of inflammation. Helicobacter (H.) pylori infection results in gastric immunopathology accompanied by colonization of stomachs with bacterial species, which are usually restricted to the lower intestine. Potential microbiota shifts distal to the inflammatory process following long-term H. pylori infection, however, have not been studied so far.
  
  
  RESULTS
  For the first time, we investigated microbiota changes along the entire GI tract of Mongolian gerbils after 14 months of infection with H. pylori B8 wildtype (WT) or its isogenic ΔcagY mutant (MUT) strain which is defective in the type IV secretion system and thus unable to modulate specific host pathways. Comprehensive cultural analyses revealed that severe gastric diseases such as atrophic pangastritis and precancerous transformations were accompanied by elevated luminal loads of E. coli and enterococci in the caecum and together with Bacteroides/Prevotella spp. in the colon of H. pylori WT, but not MUT infected gerbils as compared to naïve animals. Strikingly, molecular analyses revealed that Akkermansia, an uncultivable species involved in mucus degradation, was exclusively abundant in large intestines of H. pylori WT, but not MUT infected nor naïve gerbils.
  
  
  CONCLUSIONS
  Taken together, long-term infection of Mongolian gerbils with a H. pylori WT strain displaying an intact type IV secretion system leads to distinct shifts of the microbiota composition in the distal uninflamed, but not proximal inflamed GI tract. Hence, H. pylori induced immunopathogenesis of the stomach, including hypochlorhydria and hypergastrinemia, might trigger large intestinal microbiota changes whereas the exact underlying mechanisms need to be further unraveled.
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Plickert
authors.affiliation: German Research Center for Environmental Health, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Wiedemann
authors.affiliation: Department of Pathology/Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Ulf B
authors.initials: UB
authors.lastname: Göbel
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Division of Molecular Biology, Department of Microbiology, University of Salzburg, Salzburg, Austria.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Rieder
mesh_terms: D000126:Achlorhydria / Q000150:complications / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D000818:Animals; D058947:Bacterial Secretion Systems / Q000276:immunology; D001439:Bacteroides / Q000276:immunology / Q000472:pathogenicity; D002693:Chlamydiaceae / Q000276:immunology / Q000472:pathogenicity; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D005260:Female; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity*; D007113:Immunity, Innate; D007420:Intestine, Large / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D064307:Microbiota / Q000276:immunology*; D018720:Prevotella / Q000276:immunology / Q000472:pathogenicity; D013270:Stomach / Q000276:immunology / Q000382:microbiology* / Q000473:pathology
chemical_list: D058947:Bacterial Secretion Systems