The gut-bone axis in ankylosing spondylitis: mechanistic insights and the translational gap

The gut-bone axis is pivotal in the pathogenesis of ankylosing spondylitis (AS), with gut dysbiosis and mucosal immune activation driving skeletal pathology. However, translating these mechanistic insights into effective therapies remains challenging. This review critically analyzes this translational gap, arguing that the therapeutic paradoxes seen with cytokine inhibitors and microbiome-targeted therapies are a direct consequence of the disease's significant variability. We focus on the unexpected failure of IL-23 inhibitors and the dual effects of IL-17 blockade to illustrate the need for a nuanced understanding of tissue-specific immunity. We then propose a biomarker-driven, AI-assisted therapeutic framework that integrates multi-omic data to personalize AS treatment, aiming to bridge the gap between mechanistic insights and clinical success and offer a path toward progression-free remission.