Changes in the Gut Microbiome Contribute to the Development of Behcet's Disease <i>via</i> Adjuvant EffectsOriginal paper
What was studied?
Researchers tested whether the gut microbiome of Behcet's disease (BD) patients can directly promote autoimmune disease. Pooled stool from five active ocular BD patients and five matched healthy controls was transplanted into B10.RIII mice by oral gavage.
How was it studied?
After fecal transplantation, mice were assessed for short chain fatty acids, gut barrier proteins, serum LPS, and immune cell activity. Splenic neutrophils and CD4+ T cells were profiled by single cell RNA sequencing. BD-recipient mice were then given experimental autoimmune uveitis (EAU) or encephalomyelitis (EAE) to test whether the transplanted microbiome worsened disease.
What did they find?
BD-recipient mice had lower fecal butyric acid, propionic acid, and valeric acid, along with reduced tight junction proteins Claudin-1, Claudin-4, and Occludin and higher serum LPS. These mice showed more splenic neutrophils, enriched innate immune genes, and increased Th1 and Th17 cell differentiation in mesenteric lymph nodes and spleen. BD-recipient mice also developed more severe EAU by day 14 and more severe EAE beginning around day 19.
Why it matters
The findings suggest the BD gut microbiome can act as an immunological adjuvant, worsening autoimmune disease through increased gut permeability and heightened innate and Th1/Th17 immunity. This supports gut microbiome manipulation as a potential avenue for treating BD and possibly other autoimmune conditions.