Altering the gut microbiota ameliorates experimental autoimmune uveitis

Abstract

 

Purpose

 

The gut microbiota appear to be important in the regulation of a number of immune-mediated diseases including multiple sclerosis, diabetes mellitus, and inflammatory bowel disease, but the relationship between the gut microbiome and autoimmune uveitis has not yet been determined. The objective of this study was to investigate whether altering the gut microbiota with broad-spectrum antibiotics affects the severity of experimental autoimmune uveitis (EAU).

 

Methods

 

Interphotoreceptor binding protein (IRBP) peptide 161-180 was used to induce uveitis in B10.RIII mice. Mice were treated with oral or intraperitoneal (ip) antibiotics (1 mg/mL each of ampicillin, neomycin sulfate, and metronidazole, 0.5 mg/mL of vancomycin) starting 1 week prior to antigen challenge. Eyes, spleen, cervical and mesenteric lymph nodes (CLN, MLN), and lamina propia lymphocytes (LPL) were collected on day 20-21. We performed clinical and histological grading of eyes, as well as flow cytometry analysis for quantifying regulatory T-cell (Treg) populations.

 

Results

 

A smaller proportion of antibiotic-fed animals had clinical EAU scores ≥ 2.5 compared with water-fed animals (7.7% vs 46.1%, p=0.048, OR=9.0) (Fig. 1a). The histopathological EAU scores followed a similar trend with 22.2% eyes in the antibiotic-fed group compared to 76.9% eyes in the water-fed group developing a score ≥ 2.5 (p=0.011, OR=11.67, Fig. 1b). No significant difference in scores was found between ip antibiotic compared to ip control groups (clinical: 33% vs. 44.4%, p=0.625, OR=0.629; histopathological: 50% vs 75%, p=0.302, OR=0.33). There were higher proportions of Treg (CD4+, FoxP3+) cells in the CLN, MLN, spleen, and LPL of oral antibiotic-fed mice compared to water-fed mice.

 

Conclusions

 

Our results suggest that alteration of the gut microbiota by oral antibiotic administration modulates the development of EAU. Further investigation of the Treg populations associated with the gut microbial change will be warranted to determine the underlying mechanism.

 

 

Fig. 1. Altering the gut microbiota ameliorates EAU in B10.RIII mice.(A) Clinical scores at peak inflammation (day 13-14) in 3 experiments (n=4-5, each experiment)(B) Histological scores at the end of the experiment (day 20-21) in 2 experiments (n=4-5, each experiment).

 

Keywords: 746 uveitis-clinical/animal model • 432 autoimmune disease