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Title: Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis

Abstract

The bacteria that live normally in our intestinal tract, or the gut microbiota contribute to the pathogenesis of extra intestinal autoimmune disease via their ability to dynamically educate the immune system. For example, in a mouse model of relapsing, remitting multiple sclerosis (MS), experimental autoimmune encephalomyelitis or EAE, several studies demonstrated that commensal microorganisms are essential in causing clinical disease activity. Interestingly, MS patients have a distinct gut microbiota to healthy controls. Several studies have also illustrated the importance of the gut microbiome in the development of other diseases, including Type 1 diabetes, metabolic syndrome, rheumatoid arthritis, and ankylosing spondylitis. Furthermore, HLA=B27 transgenic rats, which develop spontaneous spondyloarthropathy analogous to patients who have ankylosing spondylitis, associated with uveitis in humans, do not develop intestinal or peripheral join inflammation when raised in a germ-free environment. Our group has shown that HLA-B27 transgenic rats have an altered intestinal microbiota compared to healthy control rats. Given the similarities between the central nervous system (CNS) and the retina, as well as co-expression of potentially immunogenic self-antigens from the CNS and joint in the eye, we hypothesized that modulating the gut microbiome can result in amelioration of autoimmune uveitis. Although uveitis is a heterogeneous collectionmore » of diseases, in general immune-mediated, non-infectious, uveitis is thought to be due to a combination of genetic and environmental factors. It arises from an imbalance between the regulatory and effector arms of the immune system, result in an inappropriate immune reaction at an otherwise immune-privileged tissue site, the eye. Th1 and Th17 T lymphocytes are examples of effector immune cell subsets that my contribute to inflammatory disease of the eye, whereas regulatory T cells (Tregs) are an example of a regulatory immune cell subset that is typically required to downregulate an immune response to prevent uncontrolled disease. Experimental autoimmune uveitis (EAU) is a very robust, widely use model of T lymphoocyte mediated uveitis that can be induced in a certain strains of mice (e.g. B10.RIII) by immunizing these animals with a specific retinal antigen, interphotoreceptor binding protein (IRBP), but requires co-administration of an adjuvant containing killed Mycobacterium antigen. Lastly, this model of inducible uveitis is analogous to the EAE model of demyelinating disease mentioned above. EAU is a thought to be predominantly Th1 and Th17 mediated.« less

Authors:
 [1];  [1];  [2];  [3];  [1];  [1];  [1];  [4];  [4];  [5];  [1]
+ Show Author Affiliations
  1. Oregon Health and Science Univ., Portland, OR (United States). Casey Eye Inst.
  2. Oregon Health and Science Univ., Portland, OR (United States). Dept. of Medical Informatics and Clinical Epidemiology
  3. Oregon Health and Science Univ., Portland, OR (United States). Division of Rheumatology, Dept. of Medicine
  4. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  5. Oregon Health and Science Univ., Portland, OR (United States). Casey Eye Inst.; Oregon Health and Science Univ., Portland, OR (United States). Division of Rheumatology, Dept. of Medicine; Devers Eye Inst., Portland, OR (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1353349
Report Number(s):
PNNL-SA-117611
Journal ID: ISSN 1552-5783
Grant/Contract Number:  
AC05-76RL01830; K08 EY022948; K12HD043488; P30 EY010572
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Investigative Opthalmology & Visual Science
Additional Journal Information:
Journal Volume: 57; Journal Issue: 8; Journal ID: ISSN 1552-5783
Publisher:
Association for Research in Vision and Ophthalmology
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; microbial; autoimmune uveitis; microbiome; uveitis; antibiotics; regulatory T cells

Citation Formats

Nakamura, Yukiko K., Metea, Christina, Karstens, Lisa, Asquith, Mark, Gruner, Henry, Moscibrocki, Cathleen, Lee, Iris, Brislawn, Colin J., Jansson, Janet K., Rosenbaum, James T., and Lin, Phoebe. Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis. United States: N. p., 2016. Web. doi:10.1167/iovs.16-19733.
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Nakamura, Yukiko K., Metea, Christina, Karstens, Lisa, Asquith, Mark, Gruner, Henry, Moscibrocki, Cathleen, Lee, Iris, Brislawn, Colin J., Jansson, Janet K., Rosenbaum, James T., & Lin, Phoebe. Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis. United States. https://doi.org/10.1167/iovs.16-19733
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Nakamura, Yukiko K., Metea, Christina, Karstens, Lisa, Asquith, Mark, Gruner, Henry, Moscibrocki, Cathleen, Lee, Iris, Brislawn, Colin J., Jansson, Janet K., Rosenbaum, James T., and Lin, Phoebe. Fri . "Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis". United States. https://doi.org/10.1167/iovs.16-19733. https://www.osti.gov/servlets/purl/1353349.
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@article{osti_1353349,
title = {Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis},
author = {Nakamura, Yukiko K. and Metea, Christina and Karstens, Lisa and Asquith, Mark and Gruner, Henry and Moscibrocki, Cathleen and Lee, Iris and Brislawn, Colin J. and Jansson, Janet K. and Rosenbaum, James T. and Lin, Phoebe},
abstractNote = {The bacteria that live normally in our intestinal tract, or the gut microbiota contribute to the pathogenesis of extra intestinal autoimmune disease via their ability to dynamically educate the immune system. For example, in a mouse model of relapsing, remitting multiple sclerosis (MS), experimental autoimmune encephalomyelitis or EAE, several studies demonstrated that commensal microorganisms are essential in causing clinical disease activity. Interestingly, MS patients have a distinct gut microbiota to healthy controls. Several studies have also illustrated the importance of the gut microbiome in the development of other diseases, including Type 1 diabetes, metabolic syndrome, rheumatoid arthritis, and ankylosing spondylitis. Furthermore, HLA=B27 transgenic rats, which develop spontaneous spondyloarthropathy analogous to patients who have ankylosing spondylitis, associated with uveitis in humans, do not develop intestinal or peripheral join inflammation when raised in a germ-free environment. Our group has shown that HLA-B27 transgenic rats have an altered intestinal microbiota compared to healthy control rats. Given the similarities between the central nervous system (CNS) and the retina, as well as co-expression of potentially immunogenic self-antigens from the CNS and joint in the eye, we hypothesized that modulating the gut microbiome can result in amelioration of autoimmune uveitis. Although uveitis is a heterogeneous collection of diseases, in general immune-mediated, non-infectious, uveitis is thought to be due to a combination of genetic and environmental factors. It arises from an imbalance between the regulatory and effector arms of the immune system, result in an inappropriate immune reaction at an otherwise immune-privileged tissue site, the eye. Th1 and Th17 T lymphocytes are examples of effector immune cell subsets that my contribute to inflammatory disease of the eye, whereas regulatory T cells (Tregs) are an example of a regulatory immune cell subset that is typically required to downregulate an immune response to prevent uncontrolled disease. Experimental autoimmune uveitis (EAU) is a very robust, widely use model of T lymphoocyte mediated uveitis that can be induced in a certain strains of mice (e.g. B10.RIII) by immunizing these animals with a specific retinal antigen, interphotoreceptor binding protein (IRBP), but requires co-administration of an adjuvant containing killed Mycobacterium antigen. Lastly, this model of inducible uveitis is analogous to the EAE model of demyelinating disease mentioned above. EAU is a thought to be predominantly Th1 and Th17 mediated.},
doi = {10.1167/iovs.16-19733},
url = {https://www.osti.gov/biblio/1353349}, journal = {Investigative Opthalmology & Visual Science},
issn = {1552-5783},
number = 8,
volume = 57,
place = {United States},
year = {2016},
month = {7}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1167/iovs.16-19733
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Works referencing / citing this record:

The microbiome and ophthalmic disease
journal, November 2018

The microbiome and ophthalmic disease
journal, November 2018

Antibiotic-Induced Disruption of Gut Microbiota Alters Local Metabolomes and Immune Responses
journal, April 2019

The Gut–Eye Axis: Lessons Learned from Murine Models
journal, July 2020

Visions of Eye Commensals: The Known and the Unknown About How the Microbiome Affects Eye Disease
journal, October 2018

Alterations in gut bacterial and fungal microbiomes are associated with bacterial Keratitis, an inflammatory disease of the human eye
journal, October 2018

The microbiome and HLA-B27-associated acute anterior uveitis
journal, October 2018

Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine
journal, September 2017

Commensal microbiota as a potential trigger of autoimmune uveitis
journal, February 2017

Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site
journal, November 2016

Importance of the intestinal microbiota in ocular inflammatory diseases: A review
journal, March 2019

Microbiome and Autoimmune Uveitis
journal, February 2019

Systemic Antibiotic Therapy Reduces Circulating Inflammatory Dendritic Cells and Treg–Th17 Plasticity in Periodontitis
journal, April 2019

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