{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T18:50:54Z","timestamp":1777056654530,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":208,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Beyond intestinal inflammation, inflammatory bowel disease (IBD) is associated with many extraintestinal manifestations, particularly arthritis. However, systematic evidence regarding causal relationships between IBD and clinically prevalent arthritis subtypes remains limited.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We conducted bidirectional two\u2010sample Mendelian randomization (MR) analyses to assess causal associations between IBD (Crohn\u2019s disease [CD], ulcerative colitis [UC]) and seven arthritis subtypes: rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), osteoarthritis (OA), reactive arthritis (ReA), gout and pyogenic arthritis (PA). A two\u2010step MR (TSMR) analyses was subsequently performed to evaluate potential mediators across four domains: metabolites of gut microbiota, serum biochemical indicators, inflammatory\/immune factors, and nutritional\/metabolic indicators in IBD\u2010AS\/PsA\/ReA pathways.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    MR analysis revealed that IBD increased the risk of AS (OR\u2009=\u20091.21, 95% CI: 1.11\u20131.32,\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>IVW<\/jats:sub>\n                    \u2009&lt;\u20090.001), PsA (OR\u2009=\u20091.18, 95% CI: 1.05\u20131.33,\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>IVW<\/jats:sub>\n                    \u2009=\u20090.007), and ReA (OR\u2009=\u20091.11, 95% CI: 1.04\u20131.18,\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>IVW<\/jats:sub>\n                    \u2009=\u20090.003). Subgroup analyses revealed CD increased the risk of AS (OR\u2009=\u20091.16, 95% CI: 1.07\u20131.27,\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>IVW<\/jats:sub>\n                    \u2009&lt;\u20090.001) and UC increased the risk of ReA (OR\u2009=\u20091.14, 95% CI: 1.04\u20131.24,\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>IVW<\/jats:sub>\n                    \u2009=\u20090.005). The first step of the mediation MR showed that IBD was associated with increased butyrate levels, decreased serotonin levels, increased C\u2010reactive protein (CRP), increased interleukin\u20106 (IL\u20106), increased percentage of neutrophils, decreased percentage of lymphocytes, and decreased total body bone mineral density, but the second step of the analysis revealed no significant evidence that the above factors were mediators of the causal effects of IBD on AS, PsA, and ReA.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    This study establishes the causal effect of IBD on AS, PsA, and ReA. The absence of significant mediation effects suggests that IBD\u2010associated gut dysbiosis, systemic inflammation, and calcium metabolic disturbances may not directly drive arthritis pathogenesis, challenging their utility as predictive biomarkers for arthritis development in IBD patients.\n                  <\/jats:p>","DOI":"10.1155\/mi\/1675577","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T13:05:09Z","timestamp":1753707909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of Inflammatory Factors and Calcium Metabolism With Arthritis in Patients With Inflammatory Bowel Disease: Evidence From Mediated Mendelian Randomization"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1423-2491","authenticated-orcid":false,"given":"Sinan","family":"Xiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9169-2097","authenticated-orcid":false,"given":"Kairong","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9381-2295","authenticated-orcid":false,"given":"Hongliang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3368-571X","authenticated-orcid":false,"given":"Chenyang","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9233-0856","authenticated-orcid":false,"given":"Sumei","family":"Sha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2773-4480","authenticated-orcid":false,"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2354-5209","authenticated-orcid":false,"given":"Haitao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-019-0698-1"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000392"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.07.042"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastrohep.2020.01.005"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016010098"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-021-00757-1"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05837-8"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18236"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21998"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-022-05117-0"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_2_15_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-020-01740-8"},{"key":"e_1_2_15_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-016-3374-y"},{"key":"e_1_2_15_16_2","first-page":"2860","article-title":"Spondyloarthropathy is Underestimated in Inflammatory Bowel Disease: Prevalence and HLA Association","volume":"27","author":"De Vlam K.","year":"2000","journal-title":"The Journal of Rheumatology"},{"key":"e_1_2_15_17_2","first-page":"511","article-title":"Prevalence of Ankylosing Spondylitis and Other Spondyloarthropathies Among Patients With Inflammatory Bowel Disease: A Population Study (the IBSEN Study)","volume":"29","author":"Palm O.","year":"2002","journal-title":"Journal of Rheumatology"},{"key":"e_1_2_15_18_2","first-page":"226","article-title":"Exploring the Link Between Ankylosing Spondylitis and Inflammatory Bowel Disease: A Retrospective Cohort Study","volume":"26","author":"Sharif K.","year":"2024","journal-title":"Israel Medical Association Journal"},{"key":"e_1_2_15_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20406"},{"key":"e_1_2_15_20_2","first-page":"137","article-title":"Musculoskeletal Manifestations in a Portuguese Cohort of 235 Inflammatory Bowel Disease Patients","volume":"1","author":"Fernandes B. 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