Abstract
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 the human gut and interact with each other. Although they have been shown to contribute actively to health or disease, no studies have investigated whether the fungal microbiota in AS patients is perturbed. In this study, fecal samples from 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 rRNA gene- and ITS2-based DNA sequencing. Our results showed that the microbiota of AS patients was characterized by increased abundance of Proteobacteria and decreased Bacteroidetes, which was contributed by enrichment of Escherichia-Shigella, Veillonella, Lachnospiraceae NK4A136 group, and reduction of Prevotella strain 9, Megamona, and Fusobacterium. The gut mycobiota of AS patients was characterized by higher 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, decreased ITS2/16S biodiversity ratios and altered bacterial-fungal interkingdom networks were observed in AS patients. Compared with nonsteroidal anti-inflammatory drugs (NSAIDs), treating AS patients with biological agents induced obvious changes in the gut mycobiota, and this result was highly associated with disease activity indexes, including AS disease activity index (ASDAS) C-reactive protein (asCRP), erythrocyte sedimentation rate (ESR), and Bath AS disease activity index (BASDAI). In addition, altered mycobiota in AS patients was also found associated with the degree of radiographic damage. IMPORTANCE The human gut is colonized by diverse fungi (mycobiota), and fungi have long been suspected in the pathogenesis of 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, our study is limited by sample size, and in-depth mechanism studies and additional large-scale investigations characterizing the gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.
Highlights
Intestinal bacterial dysbiosis has been increasingly linked to ankylosing spondylitis (AS), which is a prototypic and best studied subtype of spondyloarthritis (SpA)
Of the individuals with AS, 19.51% (n ϭ 8) were newly diagnosed as having AS and 80.49% (n ϭ 33) were patients that had the disease for different lengths of time and were treated by biological agents (BLs) or nonsteroidal anti-inflammatory drug (NSAIDs)
Saccharomyces followed a complicated inverse correlation with several bacterial genera in the BL group. These results suggested a complex relationship between the bacteria and fungi in the gut microbiota and that specific alterations were present in patients receiving different therapeutic regimens
Summary
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 the human gut and interact with each other They have been shown to contribute actively to health or disease, no studies have investigated whether the fungal microbiota in AS patients is perturbed. Fecal samples from 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 rRNA gene- and ITS2-based DNA sequencing. A distinct alteration of fungal microbiota (mycobiota) was identified in fecal samples from IBD patients [19]. Many studies have reported fungal microbiota dysbiosis in IBD [19, 28,29,30,31,32], no research has investigated whether the fungal microbiota in AS patients is perturbed
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