Gut microbial interaction networks control autoimmunity to neuroretina

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• The gut microbiome plays a crucial role in immune-mediated inflammatory diseases.
• Autoimmune uveitis is an ocular inflammation driven by T cells.
• Previous studies indicated gut commensals trigger experimental autoimmune uveitis (sEAU).

Purpose of the Study:

• To investigate the role of gut microbes in autoimmune uveitis.
• To identify specific microbial and metabolic changes associated with uveitis.
• To explore the mechanisms by which gut bacteria influence ocular autoimmunity.

Main Methods:

• Colonization of germ-free mice with human gut flora.
• Analysis of microbiome composition, metabolite levels (short-chain fatty acids - SCFAs), and immune responses (Th1).
• Mechanistic gain-of-function experiments using Akkermansia enrichment.

Main Results:

• Human gut flora induced uveitis in germ-free mice.
• Uveitis severity correlated with increased Akkermansia, decreased SCFA-producing Firmicutes, lower SCFA levels, and a dominant gut Th1 response.
• Akkermansia enrichment exacerbated disease and reproduced observed phenotype shifts.
• An inverse correlation between Akkermansia and Firmicutes was observed in human patients with uveitis, multiple sclerosis, and Crohn's disease.

Conclusions:

• Akkermansia may promote autoimmunity by outcompeting SCFA producers and enhancing Th1 responses.
• Gut microbial composition and metabolite profiles are linked to autoimmune diseases.
• These findings suggest a conserved ecological mechanism of gut microbiome modulation of systemic immune balance and autoimmune diseases.