title: Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis.
abstract: To investigate the contribution of the gut microbiota to the pathogenesis of uveitis.
  
  
  
  Experimental autoimmune uveitis (EAU) in B10.RIII mice was induced using interphotoreceptor binding protein peptide. Mice were treated with oral or intraperitoneal (IP) antibiotics. Effector (Teff) and regulatory (Treg) T lymphocytes were identified using flow cytometry; 16S rRNA gene sequencing and qPCR were performed on gastrointestinal (GI) contents.
  
  
  
  Broad-spectrum (four antibiotics given simultaneously) oral, but not IP, antibiotics reduced mean uveitis clinical scores significantly compared with water-treated animals (0.5 vs. 3.0, P < 0.0001 for oral; 3.4 vs. 3.4, P > 0.99 for IP). Both oral metronidazole (P = 0.02) and vancomycin (P < 0.0001) alone decreased inflammation, whereas neomycin (P = 0.7) and ampicillin (P = 0.4) did not change mean uveitis scores. Oral broad-spectrum antibiotics increased Tregs in the GI lamina propria of EAU animals at 1 week, and in extraintestinal lymphoid tissues later, whereas Teff and inflammatory cytokines were reduced. 16S sequencing of GI contents revealed altered microbiota in immunized mice compared with nonimmunized mice, and microbial diversity clustering in EAU mice treated with uveitis-protective antibiotics. Experimental autoimmune uveitis mice also demonstrated gut microbial diversity clustering associated with clinical score severity.
  
  
  
  Oral antibiotics modulate the severity of inducible EAU by increasing Tregs in the gut and extraintestinal tissues, as well as decreasing effector T cells and cytokines. 16S sequencing suggests that there may be protective and, conversely, potentially uveitogenic, gut microbiota. These findings may lead to a better understanding of how uveitis can be treated or prevented by modulating the gut microbiome.
authors.affiliation: Casey Eye Institute Oregon Health and Science University, Portland, Oregon, United States.
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Nakamura
authors.affiliation: Casey Eye Institute Oregon Health and Science University, Portland, Oregon, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Metea
authors.affiliation: Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Karstens
authors.affiliation: Division of Rheumatology, Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Asquith
authors.affiliation: Casey Eye Institute Oregon Health and Science University, Portland, Oregon, United States.
authors.forename: Henry
authors.initials: H
authors.lastname: Gruner
authors.affiliation: Casey Eye Institute Oregon Health and Science University, Portland, Oregon, United States.
authors.forename: Cathleen
authors.initials: C
authors.lastname: Moscibrocki
authors.affiliation: Casey Eye Institute Oregon Health and Science University, Portland, Oregon, United States.
authors.forename: Iris
authors.initials: I
authors.lastname: Lee
authors.affiliation: Pacific Northwest National Laboratory, Richland, Washington, United States.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Brislawn
authors.affiliation: Pacific Northwest National Laboratory, Richland, Washington, United States.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Jansson
authors.affiliation: Casey Eye Institute Oregon Health and Science University, Portland, Oregon, United States 3Division of Rheumatology, Department of Medicine, Oregon Health and Science University, Portland, Oregon, United States 5Devers Eye Institute, Portland, Oregon, Uni.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.affiliation: Casey Eye Institute Oregon Health and Science University, Portland, Oregon, United States.
authors.forename: Phoebe
authors.initials: P
authors.lastname: Lin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000382:microbiology* / Q000517:prevention & control; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004338:Drug Combinations; D005136:Eye Proteins / Q000633:toxicity; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000276:immunology*; D007274:Injections, Intraperitoneal; D008815:Mice, Inbred Strains; D012160:Retina / Q000276:immunology / Q000382:microbiology; D012177:Retinol-Binding Proteins / Q000633:toxicity; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014605:Uveitis / Q000382:microbiology* / Q000517:prevention & control; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D016207:Cytokines; D004338:Drug Combinations; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial