July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Duration of antibiotic treatment affects gut microbiota and intestinal immunity, and determines susceptibility to ocular autoimmunity
Author Affiliations & Notes
  • Ryan Salvador
    National Eye Institute, National Institutes of Health, North Bethesda, Maryland, United States
  • Reiko Horai
    National Eye Institute, National Institutes of Health, North Bethesda, Maryland, United States
  • Yingyos Jittayasothorn
    National Eye Institute, National Institutes of Health, North Bethesda, Maryland, United States
  • Rachel R Caspi
    National Eye Institute, National Institutes of Health, North Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Ryan Salvador, None; Reiko Horai, None; Yingyos Jittayasothorn, None; Rachel Caspi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2547. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ryan Salvador, Reiko Horai, Yingyos Jittayasothorn, Rachel R Caspi; Duration of antibiotic treatment affects gut microbiota and intestinal immunity, and determines susceptibility to ocular autoimmunity. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2547.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Autoimmune uveitis, thought to be driven by retina-specific T cells, is a major cause of blindness. Using a model of experimental autoimmune uveitis (EAU) induced by immunization with the retinal proteins IRBP, we have shown that long-term elimination of commensals by oral antibiotic treatment (ABX) did not affect susceptibility to EAU, but others (PMID 27415793) reported that short-term ABX was protective. To reconcile these contradictory findings, we studied how long vs. short ABX affected development of EAU, composition of gut microbiota and host-immune responses.

Methods : B10.RIII mice were treated orally with a broad spectrum antibiotic cocktail starting 12-weeks (long-term) or 1-week (short-term) prior to IRBP161-180 challenge for induction of EAU, and ABX was continued until termination of the experiment. EAU scores were evaluated by fundus examination. Fecal pellets were collected for 16S rRNA sequencing. Host-immune cell subsets from various tissues were analyzed for Th1, Th17, and Treg phenotypes as well as activation and regulatory markers.

Results : Short-term ABX delayed the onset of EAU, whereas long-term ABX did not affect the kinetics or severity of disease and showed a similar pattern to untreated SPF controls. Metagenomic analyses revealed alteration and reduction of the gut microbiota (dysbiosis) in both groups of ABX mice compared to SPF controls. Interestingly, antibiotic treatment resulted in progressive depletion of CD4+ and CD4+CD8+ T cells from the gut intraepithelial lymphocyte (IEL) compartment, such that long-term ABX mice had markedly reduced IELs compared to short-term ABX mice. Notably, IELs are thought to preserve gut mucosal barrier integrity.

Conclusions : We propose that microbiota are needed to maintain the IEL population of the gut and play a dual role in the development of uveitis. On one hand, they maintain the “protective” IEL population, but on the other hand they provide a stimulus for effector cells involved in uveitis. In this scenario, the loss of “protective” IELs after long-term ABX cancels out the benefit of reduction in bacterial mass, resulting in net zero effect on disease. A better understanding of how microbiota interacts with gut immune cells to regulate development of uveitis may lead to novel treatments for autoimmunity by manipulation of the commensal microbiome.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×