Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis

Area of Science:

• Immunology
• Microbiology
• Ophthalmology

Background:

• Uveitis is an inflammatory eye disease with complex pathogenesis.
• The gut microbiota's role in autoimmune diseases, including uveitis, is increasingly recognized.
• Understanding microbial contributions can reveal novel therapeutic targets.

Purpose of the Study:

• To investigate the gut microbiota's contribution to the pathogenesis of experimental autoimmune uveitis (EAU).
• To determine the impact of antibiotic treatment on uveitis severity and immune cell populations.

Main Methods:

• EAU was induced in B10.RIII mice using interphotoreceptor binding protein peptide.
• Mice received oral or intraperitoneal antibiotics; immune cells were analyzed via flow cytometry.
• Gut microbiota composition was assessed using 16S rRNA gene sequencing and qPCR.

Main Results:

• Oral broad-spectrum antibiotics significantly reduced uveitis clinical scores compared to controls.
• Specific antibiotics (metronidazole, vancomycin) decreased inflammation, while others did not.
• Oral antibiotics increased regulatory T cells (Tregs) and decreased effector T cells (Teffs) and inflammatory cytokines.
• 16S sequencing revealed altered gut microbiota in EAU mice, with diversity clustering associated with disease severity and antibiotic treatment.

Conclusions:

• Oral antibiotics modulate EAU severity by enhancing gut Tregs and reducing Teffs.
• Gut microbiota composition may include both protective and uveitogenic microbial communities.
• Modulating the gut microbiome offers a potential strategy for uveitis treatment and prevention.