{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T18:29:39Z","timestamp":1763058579174,"version":"3.37.3"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Soonchunhyang University Research Fund"},{"name":"Ministry of Health & Welfare","award":["HI14C2285"],"award-info":[{"award-number":["HI14C2285"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ankylosing spondylitis is a male-predominant disease and previous study revealed that estrogens have an anti-inflammatory effect on the spondyloarthritis (SpA) manifestations in zymosan-induced SKG mice. This study aimed to evaluate the effect of selective estrogen receptor modulator (SERM) lasofoxifene (Laso) on disease activity of SpA. Mice were randomized into zymosan-treated, zymosan\u2009+\u200917\u03b2-estradiol (E2)-treated, and zymosan\u2009+\u2009Laso-treated groups. Arthritis was assessed by <jats:sup>18<\/jats:sup>F-fluorodeoxyglucose (<jats:sup>18<\/jats:sup>F-FDG) small-animal positron emission tomography\/computed tomography and bone mineral density (BMD) was measured. Fecal samples were collected and 16S ribosomal RNA gene sequencing was used to determine gut microbiota differences. Both zymosan\u2009+\u2009E2-treated mice and zymosan\u2009+\u2009Laso-treated mice showed lower arthritis clinical scores and lower <jats:sup>18<\/jats:sup>F-FDG uptake than zymosan-treated mice. BMD was significantly higher in zymosan\u2009+\u2009E2-treated mice and zymosan\u2009+\u2009Laso-treated mice than zymosan-treated mice, respectively. Fecal calprotectin levels were significantly elevated at 8\u00a0weeks after zymosan injection in zymosan-treated mice, but it was not significantly changed in zymosan\u2009+\u2009E2-treated mice and zymosan\u2009+\u2009Laso-treated mice. Gut microbiota diversity of zymosan-treated mice was significantly different from zymosan\u2009+\u2009E2-treated mice and zymosan\u2009+\u2009Laso-treated mice, respectively. There was no significant difference in gut microbiota diversity between zymosan\u2009+\u2009E2-treated mice and zymosan\u2009+\u2009Laso -treated mice. Laso inhibited joint inflammation and enhanced BMD in SKG mice, a model of SpA. Laso also affected the composition and biodiversity of gut microbiota. This study provides new knowledge regarding that selected SpA patients could benefit from SERM treatment.<\/jats:p>","DOI":"10.1038\/s41598-021-91320-1","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T10:06:06Z","timestamp":1623060366000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Selective estrogen receptor modulator lasofoxifene suppresses spondyloarthritis manifestation and affects characteristics of gut microbiota in zymosan-induced SKG mice"],"prefix":"10.1038","volume":"11","author":[{"given":"Hyemin","family":"Jeong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Kyung","family":"Bae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan Hong","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang-Sung","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5391-5376","authenticated-orcid":false,"given":"Hoon-Suk","family":"Cha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"91320_CR1","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1136\/ard.2006.060293","volume":"66","author":"W Lee","year":"2007","unstructured":"Lee, W. et al. Are there gender differences in severity of ankylosing spondylitis? Results from the PSOAS cohort. Ann. Rheum. Dis. 66, 633\u2013638. https:\/\/doi.org\/10.1136\/ard.2006.060293 (2007).","journal-title":"Ann. Rheum. Dis."},{"key":"91320_CR2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.reuma.2012.09.008","volume":"9","author":"R Ortega Castro","year":"2013","unstructured":"Ortega Castro, R. et al. Different clinical expression of patients with ankylosing spondylitis according to gender in relation to time since onset of disease. Data from REGISPONSER. Reumatol. Clin. 9, 221\u2013225. https:\/\/doi.org\/10.1016\/j.reuma.2012.09.008 (2013).","journal-title":"Reumatol. Clin."},{"key":"91320_CR3","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1111\/1756-185x.12458","volume":"18","author":"H Jeong","year":"2015","unstructured":"Jeong, H. et al. Clinical characteristics of nonradiographic axial spondyloarthritis in Korea: A comparison with ankylosing spondylitis. Int. J. Rheum. Dis. 18, 661\u2013668. https:\/\/doi.org\/10.1111\/1756-185x.12458 (2015).","journal-title":"Int. J. Rheum. Dis."},{"key":"91320_CR4","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.3389\/fimmu.2018.01931","volume":"9","author":"V Taneja","year":"2018","unstructured":"Taneja, V. Sex Hormones Determine Immune Response. Front. Immunol. 9, 1931. https:\/\/doi.org\/10.3389\/fimmu.2018.01931 (2018).","journal-title":"Front. Immunol."},{"key":"91320_CR5","first-page":"497","volume":"17","author":"FJ Jimenez-Balderas","year":"1990","unstructured":"Jimenez-Balderas, F. J., Tapia-Serrano, R., Madero-Cervera, J. I., Murrieta, S. & Mintz, G. Ovarian function studies in active ankylosing spondylitis in women. Clinical response to estrogen therapy. J. Rheumatol. 17, 497\u2013502 (1990).","journal-title":"J. Rheumatol."},{"key":"91320_CR6","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.jbspin.2014.11.009","volume":"82","author":"H Jeong","year":"2015","unstructured":"Jeong, H., Bea, E. K., Lee, J., Koh, E. M. & Cha, H. S. Body mass index and estrogen predict radiographic progression in the spine in ankylosing spondylitis. Joint Bone Spine 82, 473\u2013474. https:\/\/doi.org\/10.1016\/j.jbspin.2014.11.009 (2015).","journal-title":"Joint Bone Spine"},{"key":"91320_CR7","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s13075-017-1407-9","volume":"19","author":"H Jeong","year":"2017","unstructured":"Jeong, H. et al. Estrogen attenuates the spondyloarthritis manifestations of the SKG arthritis model. Arthritis Res. Ther. 19, 198. https:\/\/doi.org\/10.1186\/s13075-017-1407-9 (2017).","journal-title":"Arthritis Res. Ther."},{"key":"91320_CR8","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/nature02119","volume":"426","author":"N Sakaguchi","year":"2003","unstructured":"Sakaguchi, N. et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426, 454\u2013460. https:\/\/doi.org\/10.1038\/nature02119 (2003).","journal-title":"Nature"},{"key":"91320_CR9","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1002\/art.34423","volume":"64","author":"M Ruutu","year":"2012","unstructured":"Ruutu, M. et al. Beta-glucan triggers spondylarthritis and Crohn\u2019s disease-like ileitis in SKG mice. Arthritis Rheum 64, 2211\u20132222. https:\/\/doi.org\/10.1002\/art.34423 (2012).","journal-title":"Arthritis Rheum"},{"key":"91320_CR10","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.jbspin.2017.11.008","volume":"85","author":"H Jeong","year":"2018","unstructured":"Jeong, H. et al. Spondyloarthritis features in zymosan-induced SKG mice. Joint Bone Spine 85, 583\u2013591. https:\/\/doi.org\/10.1016\/j.jbspin.2017.11.008 (2018).","journal-title":"Joint Bone Spine"},{"key":"91320_CR11","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nm.2817","volume":"18","author":"JP Sherlock","year":"2012","unstructured":"Sherlock, J. P. et al. IL-23 induces spondyloarthropathy by acting on ROR-\u03b3t+ CD3+CD4-CD8- entheseal resident T cells. Nat. Med. 18, 1069\u20131076. https:\/\/doi.org\/10.1038\/nm.2817 (2012).","journal-title":"Nat. Med."},{"key":"91320_CR12","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1136\/annrheumdis-2016-211064","volume":"76","author":"M Breban","year":"2017","unstructured":"Breban, M. et al. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis. Ann. Rheum. Dis. 76, 1614\u20131622. https:\/\/doi.org\/10.1136\/annrheumdis-2016-211064 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"91320_CR13","doi-asserted-by":"publisher","first-page":"3747","DOI":"10.1167\/iovs.16-19733","volume":"57","author":"YK Nakamura","year":"2016","unstructured":"Nakamura, Y. K. et al. Gut microbial alterations associated with protection from autoimmune uveitis. Invest. Ophthalmol. Vis. Sci. 57, 3747\u20133758. https:\/\/doi.org\/10.1167\/iovs.16-19733 (2016).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"91320_CR14","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/rheumatology\/kev355","volume":"55","author":"A Andersson","year":"2016","unstructured":"Andersson, A. et al. Selective oestrogen receptor modulators lasofoxifene and bazedoxifene inhibit joint inflammation and osteoporosis in ovariectomised mice with collagen-induced arthritis. Rheumatology (Oxford) 55, 553\u2013563. https:\/\/doi.org\/10.1093\/rheumatology\/kev355 (2016).","journal-title":"Rheumatology (Oxford)"},{"key":"91320_CR15","doi-asserted-by":"publisher","first-page":"S147","DOI":"10.1111\/j.1753-4887.2007.tb00353.x","volume":"65","author":"GR Mundy","year":"2007","unstructured":"Mundy, G. R. Osteoporosis and inflammation. Nutr. Rev. 65, S147-151. https:\/\/doi.org\/10.1111\/j.1753-4887.2007.tb00353.x (2007).","journal-title":"Nutr. Rev."},{"key":"91320_CR16","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1172\/jci11066","volume":"106","author":"S Cenci","year":"2000","unstructured":"Cenci, S. et al. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J. Clin. Invest. 106, 1229\u20131237. https:\/\/doi.org\/10.1172\/jci11066 (2000).","journal-title":"J. Clin. Invest."},{"key":"91320_CR17","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/pcan.2013.17","volume":"16","author":"M Garg","year":"2013","unstructured":"Garg, M. et al. Selective estrogen receptor modulators for BPH: New factors on the ground. Prostate Cancer Prostatic Dis. 16, 226\u2013232. https:\/\/doi.org\/10.1038\/pcan.2013.17 (2013).","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"91320_CR18","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1007\/s00011-005-1343-z","volume":"54","author":"T Suuronen","year":"2005","unstructured":"Suuronen, T. et al. Anti-inflammatory effect of selective estrogen receptor modulators (SERMs) in microglial cells. Inflamm. Res. 54, 194\u2013203. https:\/\/doi.org\/10.1007\/s00011-005-1343-z (2005).","journal-title":"Inflamm. Res."},{"key":"91320_CR19","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1161\/circulationaha.109.924571","volume":"122","author":"K Ensrud","year":"2010","unstructured":"Ensrud, K. et al. Lasofoxifene and cardiovascular events in postmenopausal women with osteoporosis: Five-year results from the postmenopausal evaluation and risk reduction with lasofoxifene (PEARL) trial. Circulation 122, 1716\u20131724. https:\/\/doi.org\/10.1161\/circulationaha.109.924571 (2010).","journal-title":"Circulation"},{"key":"91320_CR20","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1046\/j.1538-7836.2003.00392.x","volume":"1","author":"B Bonanni","year":"2003","unstructured":"Bonanni, B. et al. Effect of tamoxifen at low doses on ultrasensitive C-reactive protein in healthy women. J. Thromb. Haemost. 1, 2149\u20132152. https:\/\/doi.org\/10.1046\/j.1538-7836.2003.00392.x (2003).","journal-title":"J. Thromb. Haemost."},{"key":"91320_CR21","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1016\/j.imbio.2015.05.009","volume":"220","author":"AI Bernardi","year":"2015","unstructured":"Bernardi, A. I. et al. Selective estrogen receptor modulators in T cell development and T cell dependent inflammation. Immunobiology 220, 1122\u20131128. https:\/\/doi.org\/10.1016\/j.imbio.2015.05.009 (2015).","journal-title":"Immunobiology"},{"key":"91320_CR22","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1007\/s10620-011-1633-y","volume":"56","author":"T Aomatsu","year":"2011","unstructured":"Aomatsu, T. et al. Fecal calprotectin is a useful marker for disease activity in pediatric patients with inflammatory bowel disease. Dig. Dis. Sci. 56, 2372\u20132377. https:\/\/doi.org\/10.1007\/s10620-011-1633-y (2011).","journal-title":"Dig. Dis. Sci."},{"key":"91320_CR23","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1136\/flgastro-2013-100420","volume":"6","author":"A Dhaliwal","year":"2015","unstructured":"Dhaliwal, A. et al. Utility of faecal calprotectin in inflammatory bowel disease (IBD): What cut-offs should we apply?. Frontline Gastroenterol. 6, 14\u201319. https:\/\/doi.org\/10.1136\/flgastro-2013-100420 (2015).","journal-title":"Frontline Gastroenterol."},{"key":"91320_CR24","doi-asserted-by":"publisher","first-page":"71","DOI":"10.17305\/bjbms.2016.752","volume":"16","author":"A Duran","year":"2016","unstructured":"Duran, A. et al. Fecal calprotectin is associated with disease activity in patients with ankylosing spondylitis. Bosn. J. Basic Med. Sci. 16, 71\u201374. https:\/\/doi.org\/10.17305\/bjbms.2016.752 (2016).","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"91320_CR25","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1038\/4441022a","volume":"444","author":"RE Ley","year":"2006","unstructured":"Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: Human gut microbes associated with obesity. Nature 444, 1022\u20131023. https:\/\/doi.org\/10.1038\/4441022a (2006).","journal-title":"Nature"},{"key":"91320_CR26","doi-asserted-by":"publisher","first-page":"12283","DOI":"10.1038\/s41598-020-69112-w","volume":"10","author":"CH Song","year":"2020","unstructured":"Song, C. H. et al. 17\u03b2-Estradiol supplementation changes gut microbiota diversity in intact and colorectal cancer-induced ICR male mice. Sci. Rep. 10, 12283. https:\/\/doi.org\/10.1038\/s41598-020-69112-w (2020).","journal-title":"Sci. Rep."},{"key":"91320_CR27","doi-asserted-by":"publisher","first-page":"20192","DOI":"10.1038\/s41598-019-56723-1","volume":"9","author":"KD Acharya","year":"2019","unstructured":"Acharya, K. D., Gao, X., Bless, E. P., Chen, J. & Tetel, M. J. Estradiol and high fat diet associate with changes in gut microbiota in female ob\/ob mice. Sci. Rep. 9, 20192. https:\/\/doi.org\/10.1038\/s41598-019-56723-1 (2019).","journal-title":"Sci. Rep."},{"key":"91320_CR28","doi-asserted-by":"publisher","first-page":"15613","DOI":"10.1038\/s41598-017-15802-x","volume":"7","author":"R Rogier","year":"2017","unstructured":"Rogier, R. et al. Alteration of the intestinal microbiome characterizes preclinical inflammatory arthritis in mice and its modulation attenuates established arthritis. Sci. Rep. 7, 15613. https:\/\/doi.org\/10.1038\/s41598-017-15802-x (2017).","journal-title":"Sci. Rep."},{"key":"91320_CR29","doi-asserted-by":"publisher","first-page":"4632","DOI":"10.1210\/jc.2014-2222","volume":"99","author":"BJ Fuhrman","year":"2014","unstructured":"Fuhrman, B. J. et al. Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women. J. Clin. Endocrinol. Metab. 99, 4632\u20134640. https:\/\/doi.org\/10.1210\/jc.2014-2222 (2014).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"91320_CR30","doi-asserted-by":"publisher","first-page":"G118","DOI":"10.1152\/ajpgi.00024.2003","volume":"286","author":"DC Harnish","year":"2004","unstructured":"Harnish, D. C. et al. Beneficial effects of estrogen treatment in the HLA-B27 transgenic rat model of inflammatory bowel disease. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G118-125. https:\/\/doi.org\/10.1152\/ajpgi.00024.2003 (2004).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"91320_CR31","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fmicb.2011.00148","volume":"2","author":"NC Reading","year":"2011","unstructured":"Reading, N. C. & Kasper, D. L. The starting lineup: Key microbial players in intestinal immunity and homeostasis. Front. Microbiol. 2, 148. https:\/\/doi.org\/10.3389\/fmicb.2011.00148 (2011).","journal-title":"Front. Microbiol."},{"key":"91320_CR32","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1111\/jam.14588","volume":"128","author":"G Liu","year":"2020","unstructured":"Liu, G., Ma, Y., Yang, Q. & Deng, S. Modulation of inflammatory response and gut microbiota in ankylosing spondylitis mouse model by bioactive peptide IQW. J. Appl. Microbiol. 128, 1669\u20131677. https:\/\/doi.org\/10.1111\/jam.14588 (2020).","journal-title":"J. Appl. Microbiol."},{"key":"91320_CR33","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12934-020-01412-2","volume":"19","author":"X Yuan","year":"2020","unstructured":"Yuan, X., Chen, R., Zhang, Y., Lin, X. & Yang, X. Sexual dimorphism of gut microbiota at different pubertal status. Microb Cell Fact 19, 152. https:\/\/doi.org\/10.1186\/s12934-020-01412-2 (2020).","journal-title":"Microb Cell Fact"},{"key":"91320_CR34","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1002\/art.38967","volume":"67","author":"ME Costello","year":"2015","unstructured":"Costello, M. E. et al. Brief report: Intestinal dysbiosis in ankylosing spondylitis. Arthritis Rheumatol 67, 686\u2013691. https:\/\/doi.org\/10.1002\/art.38967 (2015).","journal-title":"Arthritis Rheumatol"},{"key":"91320_CR35","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1002\/art.39802","volume":"69","author":"RY Tito","year":"2017","unstructured":"Tito, R. Y. et al. Brief report: Dialister as a microbial marker of disease activity in spondyloarthritis. Arthritis Rheumatol 69, 114\u2013121. https:\/\/doi.org\/10.1002\/art.39802 (2017).","journal-title":"Arthritis Rheumatol"},{"key":"91320_CR36","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s00018-017-2693-8","volume":"75","author":"F Hugenholtz","year":"2018","unstructured":"Hugenholtz, F. & de Vos, W. M. Mouse models for human intestinal microbiota research: A critical evaluation. Cell. Mol. Life Sci. 75, 149\u2013160. https:\/\/doi.org\/10.1007\/s00018-017-2693-8 (2018).","journal-title":"Cell. Mol. Life Sci."},{"key":"91320_CR37","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3389\/fimmu.2017.00598","volume":"8","author":"Q Mu","year":"2017","unstructured":"Mu, Q., Kirby, J., Reilly, C. M. & Luo, X. M. Leaky gut as a danger signal for autoimmune diseases. Front. Immunol. 8, 598. https:\/\/doi.org\/10.3389\/fimmu.2017.00598 (2017).","journal-title":"Front. Immunol."},{"key":"91320_CR38","doi-asserted-by":"publisher","first-page":"4650","DOI":"10.4049\/jimmunol.166.7.4650","volume":"166","author":"M Salmi","year":"2001","unstructured":"Salmi, M. & Jalkanen, S. Human leukocyte subpopulations from inflamed gut bind to joint vasculature using distinct sets of adhesion molecules. J. Immunol. 166, 4650\u20134657. https:\/\/doi.org\/10.4049\/jimmunol.166.7.4650 (2001).","journal-title":"J. Immunol."},{"key":"91320_CR39","doi-asserted-by":"publisher","first-page":"2472","DOI":"10.3748\/wjg.15.2472","volume":"15","author":"MC Fantini","year":"2009","unstructured":"Fantini, M. C., Pallone, F. & Monteleone, G. Common immunologic mechanisms in inflammatory bowel disease and spondylarthropathies. World J. Gastroenterol. 15, 2472\u20132478. https:\/\/doi.org\/10.3748\/wjg.15.2472 (2009).","journal-title":"World J. Gastroenterol."},{"key":"91320_CR40","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1136\/ard.2010.149229","volume":"70","author":"P Hindryckx","year":"2011","unstructured":"Hindryckx, P. et al. Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic intestinal mucosal phenotype. Ann. Rheum. Dis. 70, 2044\u20132048. https:\/\/doi.org\/10.1136\/ard.2010.149229 (2011).","journal-title":"Ann. Rheum. Dis."},{"key":"91320_CR41","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1002\/art.39783","volume":"68","author":"Y Maeda","year":"2016","unstructured":"Maeda, Y. et al. Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol 68, 2646\u20132661. https:\/\/doi.org\/10.1002\/art.39783 (2016).","journal-title":"Arthritis Rheumatol"},{"key":"91320_CR42","doi-asserted-by":"publisher","first-page":"3841","DOI":"10.1210\/jc.2003-032058","volume":"89","author":"MR Smith","year":"2004","unstructured":"Smith, M. R., Fallon, M. A., Lee, H. & Finkelstein, J. S. Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: A randomized controlled trial. J. Clin. Endocrinol. Metab. 89, 3841\u20133846. https:\/\/doi.org\/10.1210\/jc.2003-032058 (2004).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"91320_CR43","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1210\/endo.141.4.7408","volume":"141","author":"HZ Ke","year":"2000","unstructured":"Ke, H. Z. et al. Lasofoxifene (CP-336,156), a selective estrogen receptor modulator, prevents bone loss induced by aging and orchidectomy in the adult rat. Endocrinology 141, 1338\u20131344. https:\/\/doi.org\/10.1210\/endo.141.4.7408 (2000).","journal-title":"Endocrinology"},{"key":"91320_CR44","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.1113\/JP280389","volume":"598","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. J. Physiol. 598, 3793\u20133801. https:\/\/doi.org\/10.1113\/JP280389 (2020).","journal-title":"J. Physiol."},{"key":"91320_CR45","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ygcen.2011.11.014","volume":"175","author":"E Ingberg","year":"2012","unstructured":"Ingberg, E., Theodorsson, A., Theodorsson, E. & Strom, J. O. Methods for long-term 17\u03b2-estradiol administration to mice. Gen. Comp. Endocrinol. 175, 188\u2013193. https:\/\/doi.org\/10.1016\/j.ygcen.2011.11.014 (2012).","journal-title":"Gen. Comp. Endocrinol."},{"key":"91320_CR46","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1002\/art.34423","volume":"64","author":"M Ruutu","year":"2012","unstructured":"Ruutu, M. et al. \u03b2-glucan triggers spondylarthritis and Crohn\u2019s disease-like ileitis in SKG mice. Arthritis Rheum. 64, 2211\u20132222. https:\/\/doi.org\/10.1002\/art.34423 (2012).","journal-title":"Arthritis Rheum."},{"key":"91320_CR47","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/nar\/gks808","volume":"41","author":"A Klindworth","year":"2013","unstructured":"Klindworth, A. et al. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 41, e1. https:\/\/doi.org\/10.1093\/nar\/gks808 (2013).","journal-title":"Nucleic Acids Res."},{"key":"91320_CR48","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","volume":"37","author":"E Bolyen","year":"2019","unstructured":"Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37, 852\u2013857. https:\/\/doi.org\/10.1038\/s41587-019-0209-9 (2019).","journal-title":"Nat. Biotechnol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91320-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91320-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91320-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T09:34:02Z","timestamp":1670060042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91320-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["91320"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-91320-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2021,6,7]]},"assertion":[{"value":"6 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11923"}}