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Helicobacter bilis Colonization Enhances Susceptibility to Typhlocolitis Following an Inflammatory Trigger

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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.

Aim

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Room 2182, Ames, IA, 50011-1250, USA

    Zhiping Liu, Amanda E. Ramer-Tait, Abigail L. Henderson & Michael J. Wannemuehler

  2. Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA

    Chong Wang

  3. Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, USA

    Jesse M. Hostetter

  4. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA

    Albert E. Jergens

  5. Department of Statistics, College of Liberal Arts and Sciences, Iowa State University, Ames, IA, USA

    Cumhur Yusuf Demirkale, Dan Nettleton & Chong Wang

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  1. Zhiping Liu
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  2. Amanda E. Ramer-Tait
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Correspondence to Michael J. Wannemuehler.

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Liu, Z., Ramer-Tait, A.E., Henderson, A.L. et al. Helicobacter bilis Colonization Enhances Susceptibility to Typhlocolitis Following an Inflammatory Trigger. Dig Dis Sci 56, 2838–2848 (2011). https://doi.org/10.1007/s10620-011-1701-3

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  • DOI: https://doi.org/10.1007/s10620-011-1701-3

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