Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis

Abstract

BackgroundThe assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease.ResultsTo investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentially abundant between ankylosing spondylitis patients and healthy controls. Patients were characterized by a form of gut microbial dysbiosis that is more prominent than previously reported cases with inflammatory bowel disease. Specifically, the ankylosing spondylitis patients demonstrated increases in the abundance of Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus, which is commonly used in probiotics, accumulated in the ankylosing spondylitis patients. Diagnostic algorithms were established using a subset of these gut microbial biomarkers.ConclusionsAlterations of the gut microbiome are associated with development of ankylosing spondylitis. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1271-6) contains supplementary material, which is available to authorized users.

Compositional and functional features of the female premenopausal and postmenopausal gut microbiota

“…Previous research on the vaginal microbiome and menopause revealed that destruction of the vaginal microbiome during menopause led to lower vaginal microbiome diversity and a higher incidence of vaginalrelated diseases [30]. As shown previously in autoimmune diseases, such as ankylosing spondylitis [12] and rheumatoid arthritis [11], the gut microbiome was disturbed during the disease stage. Differences in the gut microbiome before and after menopause…”

HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome

“…Using 16S ribosomal RNA (rRNA) community profiling, we have previously demonstrated that AS patients have a discrete intestinal microbial signature in the terminal ileum compared to healthy controls (P < 0.001) (20), a finding that has subsequently been confirmed by other studies (21,22). We have also demonstrated that dysbiosis is an early feature of disease in HLA-B27transgenic rats, preceding the onset of clinical disease in the gut or joints (23).…”

“…Among several studies, some showed an increase (47), a decrease (20,21), or no change (48) in alpha diversity metrics for AS patients, and some showed an increase (22) or decrease (49) in alpha diversity for RA patients. In the present study, calculation of rarefied species richness revealed that carriage of HLA-B27 and HLA-DRB1 alleles was not associated with differences in alpha diversity except in stool samples, for which carriage of HLA-DRB1 RA risk alleles was associated with an increased alpha diversity across both cohorts ( Figure 2).…”

Effects of HLA–B27 on Gut Microbiota in Experimental Spondyloarthritis Implicate an Ecological Model of Dysbiosis

“…Our results suggest that mucus degradation by A. muciniphila , along with dysregulated goblet cell production during inflammation, may be sufficient to bring lumenal bacteria closer to the gut epithelium and promote inflammation. Similarly, Prevotella has been implicated in dysbiosis due to NLRP6 deficiency (34), colitis (30), ankylosing spondylitis (35) and psoriatic arthritis (10). Prevotella encodes enzymes (e.g.…”