IgG-seq identifies immune-reactive enteric bacteria in Crohn’s disease with spondyloarthritis

Joint inflammation is the most common extraintestinal manifestation of Crohn's disease (CD). Although alterations in the enteric microbiota are described in CD with spondyloarthritis (CD-SpA), it is not known whether distinct taxa serve as markers for clinical subtypes of axial (AxSpA) or peripheral SpA (pSpA) in CD. Moreover, it is not yet known whether these taxa generate a specific systemic IgG response. Here, we sequenced the fecal microbiome from 106 individuals (44 CD, 39 CD-SpA, 14 CD-AxSpA, and 9 healthy controls [HC]). This unique cohort revealed distinct taxonomic compositions of CD and CD-SpA compared to HC and demonstrates that the composition of the CD-AxSpA microbiome is distinct from that of CD-pSpA. Using autologous serum, we identified enteric bacteria recognized by serum IgG and demonstrate differences in the IgG coating index of specific bacterial genera associated with CD-SpA. The IgG coating index of <i>Mediterraneibacter gnavus</i> differentiated patients with CD-pSpA and is positively associated with joint disease activity. This work illustrates divergent microbiome compositions in CD-SpA subtypes, as well as the recognition of distinct enteric bacteria by serum IgG with the potential to serve as a marker of joint inflammation in CD.