Microbial signatures in psoriatic arthritis distinguish disease phenotypes and newly diagnosed inflammatory bowel disease independent of faecal calprotectin.

Abstract

There is growing evidence of microbial involvement in immune-mediated inflammatory diseases, including psoriatic arthritis (PsA) and inflammatory bowel disease (IBD). However, it remains unclear whether different PsA phenotypes exhibit distinct microbial profiles. Furthermore, up to 4% of patients with PsA have comorbid IBD, which often remains undiagnosed. We hypothesised that the gut microbiome distinguishes PsA subphenotypes and serves as a biomarker of IBD in patients with PsA independent of faecal calprotectin (fCAL). We obtained samples from 192 patients with axial or peripheral PsA and no prior diagnosis of IBD enrolled in the EISER study. Patients with elevated fCAL and subclinical IBD symptoms underwent colonoscopy with intestinal biopsy. Stool samples were used to measure fCAL, and gut microbiome was characterised using shotgun metagenomics. Serum samples were used for cytokine profiling. Axial PsA had lower alpha diversity and loss of several commensals compared with peripheral PsA, as well as a depletion of microbial biotin and arginine metabolism and higher levels of IL-23, IL-17F, and IL-8. Five subjects had newly diagnosed IBD which was characterised by a depletion of tryptophan and vitamin B6 metabolism. They also showed significant enrichment of several taxa compared to non-IBD and with a larger effect size than fCAL. Our results identify a distinct microbiome and immune profile in axial PsA, with lower microbiome diversity, a depletion of commensals and protective microbial mechanisms, and higher levels of some proinflammatory cytokines. In patients with newly diagnosed IBD, we identified microbial taxa associated with the condition yet independent of fCAL, the current clinical standard.