Microbial Signatures in Psoriatic Arthritis Distinguish Disease Phenotypes and Newly Diagnosed Inflammatory Bowel Disease Independent of Fecal Calprotectin

Objectives There is growing evidence of microbial involvement in immune-mediated diseases, including psoriatic arthritis (PsA) and inflammatory bowel disease (IBD). It is however unclear whether different PsA phenotypes exhibit distinct microbial profiles. Further, up to 4% of PsA patients have comorbid IBD, often underdiagnosed. We hypothesized that the microbiome distinguishes disease PsA sub-phenotypes and serve as a biomarker of IBD in PsA patients independent of fecal calprotectin (fCAL). Methods 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 and histology of biopsies to diagnose IBD. Stool samples were used to measure fecal calprotectin and gut microbiome using shotgun metagenomics. Blood samples were used for cytokine profiling. Results 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, with a depletion of tryptophan and vitamin B6 metabolism and enrichment of taxa discriminating them from non-IBD with a larger effect size than fCAL. Conclusion Overall, our results identify a distinct microbiome and immune profile in axial PsA, with lower microbiome diversity and depletion of protective anti-inflammatory functions compared to peripheral PsA. In newly diagnosed IBD patients, we identified microbial taxa that were independent of fecal calprotectin, the current clinical standard.