Behçet’s syndrome is a chronic, relapsing vasculitic disorder characterized by multisystem inflammation and mucosal ulceration. Despite known associations with HLA-B51 and various immunogenetic loci, the disease lacks a unifying mechanistic model that accounts for its regional clustering, immunologic features, and fluctuating clinical presentation. This paper presents a systems biology hypothesis integrating dietary, microbial, metabolic, and immunological components into a cohesive etiopathogenic framework. We propose that diet-induced microbial dysbiosis reduces SCFA production (particularly butyrate), leading to impaired secondary bile acid synthesis and suppressed FXR/TGR5 signaling. This metabolic shift results in downregulation of the homeostatic inflammasome NLRP6, increased mitochondrial ROS, and disinhibition of NLRP3 activation via the P2X7 receptor. The model further incorporates the SCFA-mediated breakdown of Treg/Th17 balance, positioning Behçet’s syndrome as a dual-path immune failure—marked by both unchecked innate priming and loss of regulatory suppression. We offer a cascade diagram illustrating this interaction and outline several testable predictions, including SCFA and bile acid profile shifts, altered NLRP and cytokine expression patterns, and mitochondrial redox dysregulation. This hypothesis reframes Behçet’s not as a primary immunogenetic disorder, but as a dynamic failure of microbial-immune metabolic integration, potentially generalizable to other mucosal autoimmune syndromes. It opens novel investigative and therapeutic directions rooted in host-microbe metabolic signaling.For questions, discussions, or collaborations, feel free to reach out via behcetsresearch@gmail.com