Too much of a good thing: Extended duration of gut microbiota depletion reverses protection from experimental autoimmune uveitis

Microbial sequencing revealed progressive reduction of gut microbiota that showed some differences in the two ABX groups compared to untreated controls. Interestingly, duration of ABX was associated with a gradual disappearance of the CD4+ and CD4+CD8+ subset of gut intraepithelial lymphocytes (IELs). This IEL subset is microbiota-dependent and is absent in germ-free mice. Relative abundance of Lactobacillus reuteri correlated with frequencies of CD4+CD8+ IELs and reduced EAU. Notably, IELs in culture suppressed antigen-specific activation of autoreactive T cells. EAU-susceptible B10.RIII mice were treated orally with a broad-spectrum antibiotic cocktail starting at least 4-weeks (long-term) or 1-week (short-term) before IRBP161-180 immunization until the termination of the experiment. Gut microbiota were characterized by 16S amplicon sequencing and host gut immune elements were studied phenotypically and functionally.