Microbiome Biomarker May Flag Spondyloarthritis in Crohn’s

TOPLINE:

The level of immunoglobulin G (IgG) seroreactivity to unique enteric microbiota in patients with Crohn’s disease (CD) may differentiate those with spondyloarthritis (SpA) from those without and also distinguish peripheral from axial joint disease activity.

METHODOLOGY:

• Researchers analyzed the enteric microbiome in individuals with CD, with or without axial SpA or peripheral SpA, using a process called IgG-seq that identifies enteric bacteria coated by serum IgG.
• They included 1src6 participants: 44 with CD (median age, 35 years; 68% women), 39 with CD and peripheral SpA (median age, 34 years; 64% women), 14 with CD and axial SpA (median age, 37 years; 71% women), and nine healthy control individuals (median age, 35 years; 55% women).
• Axial SpA and peripheral SpA were defined using clinical and/or radiographic criteria established by the Assessment of Spondyloarthritis International Society. Joint disease activity was assessed using the bath ankylosing spondylitis disease activity index.
• IgG-seq was used to identify enteric bacteria coated with systemic IgG in those with extraintestinal manifestations of CD by incubating autologous serum with stool samples. The antibody-coated bacteria were sequenced to identify those associated with different populations and to evaluate their potential as diagnostic markers for SpA in patients with CD.
• Fecal microbiome sequencing was performed using 16S ribosomal ribonucleic acid sequencing, and the IgG coating index was calculated to assess differences in bacterial recognition.

TAKEAWAY:

• Compared with healthy individuals, alpha diversity analysis showed a reduced gut microbiome diversity in patients with CD (P=.src18) and those with CD and SpA (P=.src25). Significant differences in Shannon diversity (P=.src33) and beta diversity (P=.src37) were noted between patients with CD and axial SpA and those with CD and peripheral SpA despite having similar disease activity scores.
• Linear discriminant effect size analysis showed enrichment of Escherichia-Shigella and Bacteroides in patients with CD and peripheral SpA vs those with CD and axial SpA; it also showed enrichment of Prevotella in patients with CD and axial SpA vs those with CD and peripheral SpA.
• IgG coating of Mediterraneibacter gnavus was higher in those with CD and SpA — at 33% in those with peripheral SpA and 29% in those with axial SpA — than in those with CD and healthy individuals (11%). Among patients with CD and peripheral SpA, the IgG coating index of M gnavus was associated with joint disease activity (P=.srcsrc3).
• The IgG coating index for certain bacteria, including M gnavus, used to generate receiver operating characteristic curves could differentiate between CD with axial SpA and CD with peripheral SpA, with an area under the curve of 83%, and could serve as potential markers.

IN PRACTICE:

“Increased recognition of M gnavus specifically in individuals with CD-SpA from this cohort provides further evidence for closer study of this organism in the setting of CD-SpA and other autoimmune disease,” the authors wrote.

SOURCE:

This study, led by Grace A. Maldarelli, MD, PhD, Weill Cornell Medicine in New York City, was published online on February 13, 2src25, in Gut Microbes.

LIMITATIONS:

The study was limited by its single cohort design, necessitating additional validation cohorts with both human leukocyte antigen (HLA)-B27–negative and HLA-B27–positive CD with axial SpA to assess the diagnostic value of the study findings. Further research is needed to explore the medication-specific effect of anti–tumor necrosis factor alpha and anti-interleukin 12/23 therapies and elucidate the immunologic mechanisms by which M gnavus contributes to CD with SpA.

DISCLOSURES:

This study was funded by a National Institutes of Health training grant and the Weill Cornell Clinical and Translational Science Center grant. One author declared receiving support from the Weill Cornell Department of Medicine Fund for the Future Award. Some authors reported having financial relationships with pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.