Gut microbiota translocation promotes autoimmune cholangitis

Hong Di Ma, Zhi Bin Zhao, Wen Tao Ma, Qing Zhi Liu, Cai Yue Gao, Liang Li, Jinjun Wang, Koichi Tsuneyama, Bin Liu, Weici Zhang, Yongjian Zhou, M. Eric Gershwin, Zhe Xiong Lian

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Gut microbiota and bacterial translocation have been implicated as significant contributors to mucosal immune responses and tolerance; alteration of microbial molecules, termed pathogen-associated molecular patterns (PAMP) and bacterial translocation are associated with immune pathology. However, the mechanisms by which dysregulated gut microbiota promotes autoimmunity is unclear. We have taken advantage of a well-characterized murine model of primary biliary cholangitis, dnTGFβRII mice, and an additional unique construct, toll-like receptor 2 (TLR2)-deficient dnTGFβRII mice coined dnTGFβRIITLR2−/− mice to investigate the influences of gut microbiota on autoimmune cholangitis. Firstly, we report that dnTGFβRII mice manifest altered composition of gut microbiota and that alteration of this gut microbiota by administration of antibiotics significantly alleviates T-cell-mediated infiltration and bile duct damage. Second, toll-like receptor 2 (TLR2)-deficient dnTGFβRII mice demonstrate significant exacerbation of autoimmune cholangitis when their epithelial barrier integrity was disrupted. Further, TLR2-deficiency mediates downregulated expression of tight junction-associated protein ZO-1 leading to increased gut permeability and bacterial translocation from gut to liver; use of antibiotics reduces microbiota translocation to liver and also decreases biliary pathology. In conclusion, our data demonstrates the important role of gut microbiota and bacterial translocation in the pathogenesis of murine autoimmune cholangitis.

Original languageEnglish (US)
Pages (from-to)47-57
Number of pages11
JournalJournal of Autoimmunity
Volume95
DOIs
StatePublished - Dec 1 2018

Keywords

  • Bacterial translocation
  • Fecal bacterial analysis
  • Gut microbiota
  • Gut–liver axis
  • Primary biliary cholangitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Ma, H. D., Zhao, Z. B., Ma, W. T., Liu, Q. Z., Gao, C. Y., Li, L., Wang, J., Tsuneyama, K., Liu, B., Zhang, W., Zhou, Y., Gershwin, M. E., & Lian, Z. X. (2018). Gut microbiota translocation promotes autoimmune cholangitis. Journal of Autoimmunity, 95, 47-57. https://doi.org/10.1016/j.jaut.2018.09.010