Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy upon microbiome composition

• Published in: Annals of the rheumatic diseases Vol. 79; no. 1; pp. 132 - 140
• Main Authors: Yin, Jian, Sternes, Peter Richard, Wang, Mingbang, Song, Jing, Morrison, Mark, Li, Ting, Zhou, Ling, Wu, Xin, He, Fusheng, Zhu, Jian, Brown, Matthew A, Xu, Huji
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.01.2020; Elsevier Limited
• Subjects: Adult; Ankylosing Spondylitis; Anti-TNF; Arthritis; Asian People; Bacteria; Case-Control Studies; China; Cross Reactions; Disease; Dysbacteriosis; Dysbiosis - immunology; Dysbiosis - microbiology; Epitopes; Epitopes - immunology; Female; Gastrointestinal Microbiome - genetics; Gastrointestinal Microbiome - immunology; Histocompatibility antigen HLA; HLA-B27 Antigen - immunology; Hospitals; Humans; Immune system; Inflammatory bowel disease; Intestinal microflora; Lymphocytes; Male; Metagenome; Metagenomics; Microbiomes; Microbiota; Middle Aged; Peptides; Peptides - immunology; Single-nucleotide polymorphism; Species; Spondylitis; Spondylitis, Ankylosing - drug therapy; Spondylitis, Ankylosing - immunology; Spondylitis, Ankylosing - microbiology; Spondyloarthritis; Studies; Taxonomy; TNF inhibitors; Tumor necrosis factor; Tumor Necrosis Factor Inhibitors - therapeutic use; Tumors; Young Adult; China; Beijing China; Ankylosing Spondylitis; Anti-TNF; Spondyloarthritis
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2019-215763

ObjectivesDiverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome.MethodsThe stools from a case–control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray.ResultsPrevious reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients.ConclusionThese findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.