Altered Bacterial-Fungal Interkingdom Networks in the Guts of Ankylosing Spondylitis Patients

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.

The Gut Microbiota Profile in Children with Prader–Willi Syndrome

“…Fungi and bacteria coexist in the gut; thus, their interaction networks may be altered in the disease state [ 37 ]. Alterations in bacteria–fungi interaction networks have been previously reported in colorectal cancer [ 38 ], inflammatory bowel disease [ 39 , 40 ], and ankylosing spondylitis [ 41 ]. In this study, we also noted a PWS-specific pattern for the inter-kingdom network.…”

Gut microbiota in antiviral strategy from bats to humans: a missing link in COVID-19

“…In both Crohn's disease and ulcerative colitis patients, the gut microbial diversity is significantly reduced, along with an increase in the phylum Proteobacteria, enrichment of the family Enterobacteriaceae, and depletion in the phylum Bacteroidetes (Eom et al, 2018;Franzosa et al, 2019). In ankylosing spondylitis patients, who often have subclinical gut inflammation or clinically defined inflammatory bowel disease (IBD), the gut microbiota is characterized by markedly decreased diversity, increased abundance of Proteobacteria, and decreased Bacteroidetes (Li et al, 2019). In addition, in cystic fibrosis patients who usually suffer from chronic gut inflammation, the predominant phylum is Proteobacteria (mainly Enterobacteriales), followed by Firmicutes and finally a few Bacteroidetes.…”

The Dynamic Interplay between the Gut Microbiota and Autoimmune Diseases

“…Moreover, the gut microbiota of AS patients features increasing levels of Ascomycota, especially of the class Dothideomycetes, and a decreasing abundance of Basidiomycota, mainly owing to a reduction in Agaricales. Moreover, decreased ITS2/16S biodiversity ratios and altered bacterial-fungal interkingdom networks were observed in AS patients compared with those in healthy controls [79]. Additionally, significant increases in the abundance of Erwinia and Pseudomonas and an increased prevalence of typical enteropathogens associated with ReA were found in ReA patients.…”