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Altered Bacteria-Fungi Inter-Kingdom Network in Gut of Ankylosing Spondylitis Patients

Intestinal bacterial dysbiosis has been increasingly linked to Ankylosing Spondylitis (AS), which is a prototypic and best studied subtype of Spondyloarthritis (SpA). Fungi and bacteria coexist in human gut and interact with each other, although they have been shown to contribute actively to health or diseases, no studies have investigated whether fungal microbiota in AS patients is perturbed. In this study, fecal samples of 22 AS patients, with clinical and radiographic assessments, and 16 healthy controls (HCs) were collected to systematically characterize the gut microbiota and mycobiota in AS patients by 16S rDNA and ITS2-based DNA sequencing. The relationships between therapeutic regimens, disease activity, radiographic damage of AS and gut micro/mycobiome were investigated. Our results showed a distinct mycobiota pattern in AS in addition to microbiota dysbiosis. The gut mycobiome of AS patients was characterized by higher taxonomic levels of Ascomycota, especially the class of Dothideomycetes, and decreased abundance of Basidiomycota, which was mainly contributed by the decease of Agaricales. Compared to HCs, changing of the ITS2/16S biodiversity ratio, and bacteria-fungi interkingdom network were observed in AS patients. Alteration of gut mycobiota was associated with different therapeutic regimens, disease activity, as well as different degrees of radiographic damage. Moreover, we unraveled a disease-specific interkingdom network alteration in AS. Finally, we also identified some trends suggesting that different therapeutic regimens may induce changing of both bacterial and fungal microbiota in AS. IMPORTANCE Human gut is colonized by diverse fungi (mycobiome), and they have long been suspected in the pathogenesis of Spondyloarthritis (SpA). Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, limited by sample size and indeep mechanism studies, further large scale investigations on the characterization of gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.