Disruption of Intestinal Homeostasis and Intestinal Microbiota During Experimental Autoimmune Uveitis

Cathleen Janowitz, Yukiko K. Nakamura, Christina Metea, Abigail Gligor, William Yu, Lisa Karstens, James (Jim) Rosenbaum, Mark Asquith, Phoebe Lin

Research output: Contribution to journalArticle

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Abstract

Purpose: We determine the changes in intestinal microbiota and/or disruptions in intestinal homeostasis during uveitis. Methods: Experimental autoimmune uveitis (EAU) was induced in B10.RIII mice with coadministration of interphotoreceptor retinoid-binding protein peptide (IRBP) and killed mycobacterial antigen (MTB) as an adjuvant. Using 16S rRNA gene sequencing, we looked at intestinal microbial differences during the course of uveitis, as well as intestinal morphologic changes, changes in intestinal permeability by FITC-dextran leakage, antimicrobial peptide expression in the gastrointstinal tract, and T lymphocyte prevalence before and at peak intraocular inflammation. Results: We demonstrate that increased intestinal permeability and antimicrobial peptide expression in the intestinal tract coincide in timing with increased effector T cells in the mesenteric lymph nodes, during the early stages of uveitis, before peak inflammation. Morphologic changes in the intestine were most prominent during this phase, but also occurred with adjuvant MTB alone, whereas increased intestinal permeability was found only in IRBP-immunized mice that develop uveitis. We also demonstrate that the intestinal microbiota were altered during the course of uveitis, and that some of these changes are specific to uveitic animals, whereas others are influenced by adjuvant MTB alone. Intestinal permeability peaked at 2 weeks, coincident with an increase in intestinal bacterial strain differences, peak lipocalin production, and peak uveitis. Conclusions: An intestinal dysbiosis accompanies a disruption in intestinal homeostasis in autoimmune uveitis, although adjuvant MTB alone promotes intestinal disruption as well. This may indicate a novel axis for future therapeutic targeting experimentally or clinically.

Original languageEnglish (US)
Pages (from-to)420-429
Number of pages10
JournalInvestigative ophthalmology & visual science
Volume60
Issue number1
DOIs
StatePublished - Jan 2 2019

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Uveitis
Homeostasis
Permeability
Peptides
Dysbiosis
Inflammation
Lipocalins
T-Lymphocytes
Gastrointestinal Microbiome
rRNA Genes
Intestines
Lymph Nodes
Antigens

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Disruption of Intestinal Homeostasis and Intestinal Microbiota During Experimental Autoimmune Uveitis. / Janowitz, Cathleen; Nakamura, Yukiko K.; Metea, Christina; Gligor, Abigail; Yu, William; Karstens, Lisa; Rosenbaum, James (Jim); Asquith, Mark; Lin, Phoebe.

In: Investigative ophthalmology & visual science, Vol. 60, No. 1, 02.01.2019, p. 420-429.

Research output: Contribution to journalArticle

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