Fig. 5

Chart of possible mechanisms explaining the relation between gut microbiome composition and development of Behcet’s disease. a Dysbiosis of the gut microbiome might be caused via dietary intake in individuals carrying the susceptibility genes for BD. The dysbiosis of the gut microbiome in BD is characterized by enriched sulfate-reducing bacteria (SRB) and some opportunistic pathogens in association with depleted butyrate-producing bacteria (BPB) and methanogens. b Gut metabolism in BD shows an overwhelming presence of H₂S and shortage of butyrate and methane. This abnormal environment can contribute to the intestinal epithelial barrier damage and facilitate effector molecules or pathogen-associated molecular pattern (PAMP) to invade the intestinal epithelial cells (IEC). c The PAMPs including PNG/LPS combine with their corresponding pattern recognition receptors (PRR) TLR2/TLR4 on IEC. This process leads to chronic inflammation involving hyperactivation of T helper 1 (TH1) and T helper 17 (TH17) cells in the gut. d The effector molecules or PAMP migrate to blood vessels through the hepatic circulation. Then, they recognize the receptors of TLR/TLR4 on vascular endothelial cells (VEC) and induce systemic vasculitis via the subsequent activation of TH1 and TH17 cells. e A damaged vascular endothelial barrier due to the systemic vasculitis. The effector molecules or PAMP can further migrate to organs or tissues such as the eye, joint, skin, oral, and genital mucosa though the damaged vascular endothelial barrier. Subsequently, the PAMP recognize the receptors TLR2/TLR4 in these organs or tissues, which result in various clinical manifestations of BD, such as uveitis, arthritis, skin lesions, oral, or genital ulcers. f Since oral ulcers (aphthosis) can be induced by both disturbances of the oral microbiome and dysbiosis of the gut microbiome, it presents as the most common clinical feature in BD