Native intra-articular knee microbiome is a matter of facts: a systematic review of clinical evidence

center dot Purpose: Growing interest surrounds the role of human gut microbiome in the development of degenerative pathologies such as osteoarthritis (OA), but microbes have recently been detected also in other sites previously considered to be sterile. Evidence emerged suggesting that even native and osteoarthritic knee joints may host several microbial species possibly involved in the osteoarthritic degeneration. This is the first systematic review critically collecting all the available evidence on the existence and composition of knee intra-articular microbiome. center dot Methods: A systematic research on the PubMed, Cochrane and Google Scholar databases was performed. Human clinical studies investigating the presence of intra-articular microbiome in native osteoarthritic knee joints with next-generation sequencing techniques were collected. center dot Results: A total of eight studies were included reporting data on 255 knees. All the included studies reported evidence supporting the existence of an intra-articular microbiome in native knee joints, with detection rates varying from 5.8% to 100%. Bacteria from the Proteobacteria phylum were found to be among the most identified followed by the Actinobacteria, Firmicutes, Fusobacteria, and Bacteroideta phyla. Proteobacteria phylum were also found to be more common in osteoarthritic knees when compared to healthy joints. Furthermore, several pathways correlating those microbes to knee OA progression have been suggested and summarized in this review. center dot Conclusions: Evidence collected in this systematic review suggests that the native knee joint, previously presumed to be a sterile environment, hosts a peculiar intra-articular microbiome with a unique composition. Furthermore, its alteration may have a link with the progression of knee osteoarthritis.