The gut microbiome comprises more than 3 million genes, and each person has a unique microbiome composition. While many unknown still exist, the gut microbiome seems to be tightly interlinked with the immune system and the normal functioning of our body. While a healthy microbiome is associated with a healthy host, it is also true that dysbiosis, a pertubation of the normal microbiome, is associated with diseases. In this thesis, it has been explored how osteoarthritis, joint infections, and the gut microbiome are connected. The main actors of the studies described are microorganisms. Despite being among the most studied organisms in biology, we still do not know much about the many ways they influence our life, chronic conditions such as OA, and infectious conditions such as periprosthetic joint infections. Our research started by drawing on strong preclinical evidence suggesting a gut-joint or gut-immune-joint axis in degenerative joint disease to then investigate the preliminary evidence of the role of the gut microbiome in PJI.