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

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Abstract 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.
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Microbial Signatures in Psoriatic Arthritis Distinguish Disease Phenotypes and Newly Diagnosed Inflammatory Bowel Disease Independent of Fecal Calprotectin | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Microbial Signatures in Psoriatic Arthritis Distinguish Disease Phenotypes and Newly Diagnosed Inflammatory Bowel Disease Independent of Fecal Calprotectin Alba Boix-Amorós, Kevin Bu, Rebecca Blank, Adam Cantor, Ana Gutiérrez-Casbas, and 23 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8040824/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract 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. Rheumatology microbiome rheumatology psoriatic arthritis IBD Full Text Additional Declarations The authors declare potential competing interests as follows: JUS has served as a consultant for Janssen, Novartis, Pfizer, Sanofi, Amgen, UCB, Bristol Myers Squibb Co, and AbbVie, and has received funding for investigator-initiated studies from Janssen and Pfizer. Supplementary Files EISERMicrobiome.Supplemental.20250626.docx EISERSupplementaryFigures Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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