Gut microbial interaction networks control autoimmunity to neuroretina

One such condition is autoimmune uveitis, a sight-threatening ocular inflammation driven by retina-specific T cells. Using a model of spontaneous experimental autoimmune uveitis (sEAU) we showed that gut commensals provide immune stimuli that trigger the disease.

Here we report that uveitis-promoting microbes are present in human gut flora and that colonization of germ-free (GF) mice with commensal flora from healthy human donors was sufficient to provoke disease. Severity of sEAU correlated with expansion of Akkermansia and contraction of short-chain fatty acid (SCFA)–producing Firmicutes, followed by decreased SCFA levels and a dominant gut Th1 effector response. Mechanistic gain-of-function experiments, enriching GF sEAU mice with Akkermansia, reproduced these microbiome, metabolite and immune phenotype shifts, and exacerbated disease.