Abstract
Behcet’s disease (BD) is associated with considerable gut microbiome changes. However, it still remains unknown how the composition of the gut microbiome exactly affects the development of this disease. In this study, transplantation of stool samples from patients with active ocular BD to mice via oral gavage was performed. This resulted in decreases of three short chain fatty acids (SCFAs) including butyric acid, propionic acid and valeric acid in the feces of the BD-recipient group. Intestinal barrier integrity of mice receiving BD feces was damaged as shown by a decreased expression of tight junction proteins and was associated with the release of Lipopolysaccharides (LPS) in the circulation. The mice also showed a higher frequency of splenic neutrophils as well as an enrichment of genes associated with innate immune responses in the neutrophils and CD4 + T cells as identified by single cell RNA sequencing. Analysis of neutrophils and T cells functions in these mice showed an enhanced mesenteric lymph node and splenic Th1 and Th17 cell differentiation in association with activation of neutrophils. Transplantation of BD feces to mice and subsequent induction of experimental uveitis (EAU) or encephalomyelitis (EAE) led to an exacerbation of disease in both models, suggesting a microbial adjuvant effect. These findings suggest that the gut microbiome may regulate an autoimmune response via adjuvant effects including increased gut permeability and enhancement of innate immunity.
Highlights
Behcet’s disease (BD) is a chronic, multisystemic inflammatory disorder (Zeidan et al, 2016), characterized by recurrent oral and genital ulcers, skin lesions, as well as a sight-threatening intraocular inflammation called panuveitis (Takeuchi et al, 2015)
The results showed 14 genera including Bilophila were positively associated with BD-recipient mice, whereas four genera were negatively associated with BD-recipient mice (Figure 1C)
Because an aberrant abundance of sulfate-reducing bacteria (SRB) and butyrate-producing bacteria (BPB) was found in the BD-recipient mice, we investigated the changes of short chain fatty acids (SCFAs) in the stool samples after fecal transplantation by gas chromatography-mass spectrometer analysis (GC-MS)
Summary
Behcet’s disease (BD) is a chronic, multisystemic inflammatory disorder (Zeidan et al, 2016), characterized by recurrent oral and genital ulcers, skin lesions, as well as a sight-threatening intraocular inflammation called panuveitis (Takeuchi et al, 2015). BD is thought to share both autoimmune and autoinflammatory disease features caused by an aberrant population of Th1 and Th17 cells in combination with hyper-activated neutrophils (Yamashita, 1997; Nanke et al, 2008). Changes in the gut microbiome composition are thought to contribute to the development of various immune and infectious diseases (Bevins and Salzman, 2011; de Oliveira et al, 2017; Russler-Germain et al, 2017; Domingue et al, 2020). Studies dealing with the pathogenesis of autoimmunity have suggested that the composition of the gut microbiota plays a crucial role in the development of auto-reactive lymphocytes and the recruitment of neutrophils (Littman and Rudensky, 2010). An impaired gut barrier function caused by metabolites released from the gut microbiota may facilitate this response (Wang et al, 2012; Furusawa et al, 2013)
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