{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:21:14Z","timestamp":1790241674159,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"am","delay-in-days":263,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["PR191652"],"award-info":[{"award-number":["PR191652"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K08AR070891"],"award-info":[{"award-number":["K08AR070891"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R61AR078075"],"award-info":[{"award-number":["R61AR078075"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Females have reduced osteoarthritis (OA) in surgical models. The objective of the current study was to evaluate a sex\u2010linked gut microbiome in the pathogenesis of OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We induced OA via destabilization of the medial meniscus surgery in adult male and female C57BL6\/J mice with and without opposite\u2010sex microbiome transplantation. Eight weeks later, animals were euthanized, and OA severity, synovitis, and osteophyte scores were determined. Serum lipopolysaccharide was measured chromogenically, and serum cytokines were quantified via multiplex immunoassay. Cecal microbiome profiles were generated using 16S deep sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Males had worse OA histology (3.5x, <jats:italic>P<\/jats:italic> =\u20096 \u00d7\u200910<jats:sup>\u22127<\/jats:sup>), synovitis (2.4x, <jats:italic>P<\/jats:italic> =\u20095 \u00d7\u200910<jats:sup>\u22124<\/jats:sup>), and osteophyte scores (3.7x, <jats:italic>P<\/jats:italic> =\u20093 \u00d7\u200910<jats:sup>\u22124<\/jats:sup>) than females. Male\u2010into\u2010female transplantation worsened all outcomes (histology 1.8x, <jats:italic>P<\/jats:italic> =\u20090.02; synovitis 2.0x, <jats:italic>P<\/jats:italic> =\u20093 \u00d7\u200910<jats:sup>\u22125<\/jats:sup>; osteophyte 2.1x, <jats:italic>P<\/jats:italic> =\u20090.01) compared to females, whereas female\u2010into\u2010male transplantation improved all outcomes except for synovitis (histology 0.53x, <jats:italic>P<\/jats:italic> =\u20092 \u00d7\u200910<jats:sup>\u22124<\/jats:sup>; osteophyte 0.28x, <jats:italic>P<\/jats:italic> =\u20095 \u00d7\u200910<jats:sup>\u22124<\/jats:sup>) compared to males. In the gut microbiome analysis, 44 clades were different in at least one group comparison; 5 clades were correlated with the Osteoarthritis Research Society International score (<jats:italic>Lactobacillus<\/jats:italic> R = \u22120.40, <jats:italic>Aldercreutzia<\/jats:italic> R = \u22120.40, <jats:italic>rc4_4<\/jats:italic> R = \u22120.55, <jats:italic>Sutterella<\/jats:italic> R = \u22120.37, and <jats:italic>Clostridiales<\/jats:italic> R\u00a0=\u00a00.36). In the cytokine analysis, 10 analytes were different in at least one group comparison; 3 were different in two groups (female and female\u2010into\u2010male transplants vs male comparisons, all reduced in female and female\u2010into\u2010male transplants), including interleukin\u201012 (0.66x, <jats:italic>P<\/jats:italic> =\u20090.02; 0.66x, <jats:italic>P<\/jats:italic> =\u20090.02, respectively), eotaxin (0.74x, <jats:italic>P<\/jats:italic> =\u20095 \u00d7\u200910<jats:sup>\u22126<\/jats:sup>; 0.57x, <jats:italic>P<\/jats:italic> =\u20090.03), and tumor necrosis factor \u237a (0.49x, <jats:italic>P<\/jats:italic> =\u20090.03; 0.52x, <jats:italic>P<\/jats:italic> =\u20090.009).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sex\u2010linked differences in the mouse gut microbiome are associated with OA outcomes, are reversible by opposite\u2010sex microbiome transplantation, and are associated with serum cytokine changes.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42687-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42687","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T12:54:32Z","timestamp":1693486472000},"page":"231-237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["<scp>Sex\u2010Linked<\/scp> Discrepancies in <scp>C57BL6<\/scp>\/J Mouse Osteoarthritis are Associated With the Gut Microbiome and are Transferrable by Microbiome Transplantation"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-5942","authenticated-orcid":false,"given":"Leoni","family":"Schlupp","sequence":"first","affiliation":[{"name":"Oklahoma Medical Research Foundation, Arthritis &amp; Clinical Immunology Program  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8497-6171","authenticated-orcid":false,"given":"Emmaline","family":"Prinz","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Arthritis &amp; Clinical Immunology Program and University of Oklahoma Health Sciences Center  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9617-696X","authenticated-orcid":false,"given":"Gabriella","family":"Dyson","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Arthritis &amp; Clinical Immunology Program  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1005-1401","authenticated-orcid":false,"given":"Montana","family":"Barrett","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Arthritis &amp; Clinical Immunology Program  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7561-2699","authenticated-orcid":false,"given":"Vladislav","family":"Izda","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Arthritis &amp; Clinical Immunology Program  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8611-7271","authenticated-orcid":false,"given":"Christopher M.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Arthritis &amp; Clinical Immunology Program and University of Oklahoma Health Sciences Center  Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9516-4312","authenticated-orcid":false,"given":"Matlock A.","family":"Jeffries","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Arthritis &amp; Clinical Immunology Program, University of Oklahoma Health Sciences Center, and Oklahoma City VA Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24008"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39672"},{"issue":"44","key":"e_1_2_6_4_1","first-page":"869","article-title":"Centers for Disease Control and Prevention (CDC). Prevalence of doctor\u2010diagnosed arthritis and arthritis\u2010attributable activity limitation\u2014United States, 2010\u20102012","volume":"62","year":"2013","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000353"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-017-0296-0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-022-01066-6"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.06.030"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.11.005"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0248322"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.10.002"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-6-r60"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.11.012"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12873-4"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41955"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocarto.2022.100317"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41210"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10061298"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.18831.1"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12486"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8091343"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947603518764280"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1619-7"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.196"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/art.42687","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.42687","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:27:59Z","timestamp":1759948079000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.42687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,12]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/art.42687"],"URL":"https:\/\/doi.org\/10.1002\/art.42687","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,12]]},"assertion":[{"value":"2023-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}