Gut involvement is a prominent feature of spondyloarthropathy (SpA). Analysis of immune alterations of the gut in SpA have shown two distinct aspects. On the one hand, gut inflammation in SpA seems closely related with gut inflammation seen in Crohn disease. On the other hand, gut inflammation in SpA is associated with peripheral joint inflammation. Recent studies have provided new insights into this gut-synovium axis. First, there is little new evidence to support the concept of viable microbial pathogens recirculating to the joint. In contrast, it seems likely that both bacterial antigens and reactive T cell clones home to the joint, and that adhesion molecules such as the beta7 integrins and VAP1 play an important role in this process. Second, there is increasing evidence that the different disease localizations in SpA are characterized by alterations of the innate immune system, which contribute to a breakdown of the immune tolerance and the creation of an inflammation-prone environment. Mediators of the innate immune system, such as scavenger receptors, interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-alpha), may therefore be interesting targets for therapeutic intervention, as illustrated by the effect of TNF-alpha blockade in SpA.