Digestive Diseases and Sciences

, Volume 56, Issue 10, pp 2838–2848 | Cite as

Helicobacter bilis Colonization Enhances Susceptibility to Typhlocolitis Following an Inflammatory Trigger

  • Zhiping Liu
  • Amanda E. Ramer-Tait
  • Abigail L. Henderson
  • Cumhur Yusuf Demirkale
  • Dan Nettleton
  • Chong Wang
  • Jesse M. Hostetter
  • Albert E. Jergens
  • Michael J. Wannemuehler
Original Article



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.


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.


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.


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.


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.


Helicobacter bilis Colitis Immune cells Chemotaxis Activation 



We thank Charlie Johnson, Elise Huffman, Jack Gallup, Andrea Dorn and the Iowa State University GeneChip Facility for providing technical assistance relative to the completion of these studies. This study was supported by NIH Grant K01 RR 018618 (NCRR), Crohn’s and Colitis Foundation of America, and Iowa State University Bailey Research Career Development Award.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Zhiping Liu
    • 1
  • Amanda E. Ramer-Tait
    • 1
  • Abigail L. Henderson
    • 1
  • Cumhur Yusuf Demirkale
    • 5
  • Dan Nettleton
    • 5
  • Chong Wang
    • 2
    • 5
  • Jesse M. Hostetter
    • 3
  • Albert E. Jergens
    • 4
  • Michael J. Wannemuehler
    • 1
  1. 1.Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary MedicineIowa State UniversityAmesUSA
  2. 2.Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary MedicineIowa State UniversityAmesUSA
  3. 3.Department of Veterinary Pathology, College of Veterinary MedicineIowa State UniversityAmesUSA
  4. 4.Department of Veterinary Clinical Sciences, College of Veterinary MedicineIowa State UniversityAmesUSA
  5. 5.Department of Statistics, College of Liberal Arts and SciencesIowa State UniversityAmesUSA

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