Back to Search
Start Over
Disruption of Intestinal Homeostasis and Intestinal Microbiota During Experimental Autoimmune Uveitis.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2019 Jan 02; Vol. 60 (1), pp. 420-429. - Publication Year :
- 2019
-
Abstract
- Purpose: We determine the changes in intestinal microbiota and/or disruptions in intestinal homeostasis during uveitis.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Antigens, Bacterial immunology
Autoimmune Diseases immunology
Enzyme-Linked Immunosorbent Assay
Eye Proteins
Flow Cytometry
Lipocalins metabolism
Mice
Mice, Mutant Strains
Models, Animal
Mycobacterium tuberculosis genetics
Mycobacterium tuberculosis immunology
RNA, Ribosomal, 16S genetics
Retinol-Binding Proteins
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocyte Subsets immunology
Uveitis immunology
Zonula Occludens-1 Protein metabolism
Autoimmune Diseases microbiology
Dysbiosis microbiology
Gastrointestinal Microbiome immunology
Homeostasis physiology
Intestines physiology
Uveitis microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 60
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 30695094
- Full Text :
- https://doi.org/10.1167/iovs.18-24813