title: Helicobacter bilis colonization enhances susceptibility to Typhlocolitis following an inflammatory trigger.
abstract: BACKGROUND
  Aberrant mucosal immune responses to antigens of the resident microbiota are a significant cause of inflammatory bowel diseases (IBD), as are genetic and environmental factors. Previous work from our laboratory demonstrated that Helicobacter bilis colonization of immunocompetent, defined microbiota mice induced antigen-specific immune responses to the resident microbiota, yet these mice failed to develop colitis, suggesting that the immunological provocation induced by H. bilis alone was insufficient to induce disease.
  
  
  OBJECTIVE
  The purpose of this study was to test the hypothesis that the introduction of a bacterial provocateur such as H. bilis enhances the host's susceptibility to IBD following an inflammatory event.
  
  
  METHODS
  Defined microbiota (DM) mice colonized with H. bilis were administered low dose (1.5%) dextran sodium sulfate (DSS) in drinking water for 5 days followed by a 4-day restitution period. Severity of lesions was assessed grossly and microscopically. Differential expression of select mucosal genes and histopathologic lesions was characterized.
  
  
  RESULTS
  Helicobacter bilis colonization increased the severity of intestinal inflammation induced by an inflammatory trigger in the form of low-dose DSS. An analysis of the molecular and cellular mechanisms associated with H. bilis colonization revealed significant increases in expression of mucosal genes associated with lymphocyte activation and inflammatory cell chemotaxis as well as increased infiltration of mucosal macrophages and T cells in mice colonized with H. bilis prior to DSS treatment versus DSS treatment alone.
  
  
  CONCLUSIONS
  These results indicate that prior colonization with H. bilis heightens the host's sensitivity to enteric inflammation by altering mucosal homeostasis and initiating immune cell activation and migration.
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Liu
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Ramer-Tait
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Henderson
authors.forename: Cumhur Yusuf
authors.initials: CY
authors.lastname: Demirkale
authors.forename: Dan
authors.initials: D
authors.lastname: Nettleton
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Hostetter
authors.forename: Albert E
authors.initials: AE
authors.lastname: Jergens
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000473:pathology / Q000503:physiopathology; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016998:Helicobacter / Q000472:pathogenicity / Q000502:physiology*; D016481:Helicobacter Infections / Q000150:complications* / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000473:pathology; D053706:Typhlitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D016264:Dextran Sulfate