{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:38:56Z","timestamp":1794368336201,"version":"4.9.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"7790","license":[{"start":{"date-parts":[[2019,12,25]],"date-time":"2019-12-25T00:00:00Z","timestamp":1577232000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,12,25]],"date-time":"2019-12-25T00:00:00Z","timestamp":1577232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2020,1,16]]},"DOI":"10.1038\/s41586-019-1865-0","type":"journal-article","created":{"date-parts":[[2019,12,25]],"date-time":"2019-12-25T19:02:41Z","timestamp":1577300561000},"page":"410-415","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1035,"title":["Microbial bile acid metabolites modulate gut ROR\u03b3+\u00a0regulatory T cell homeostasis"],"prefix":"10.1038","volume":"577","author":[{"given":"Xinyang","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwhan F.","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naama","family":"Geva-Zatorsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Jupp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Mathis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Benoist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis L.","family":"Kasper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,25]]},"reference":[{"key":"1865_CR1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.cmet.2017.05.008","volume":"26","author":"TS Postler","year":"2017","unstructured":"Postler, T. S. & Ghosh, S. Understanding the holobiont: how microbial metabolites affect human health and shape the immune system. Cell Metab. 26, 110\u2013130 (2017).","journal-title":"Cell Metab."},{"key":"1865_CR2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1194\/jlr.R500013-JLR200","volume":"47","author":"JM Ridlon","year":"2006","unstructured":"Ridlon, J. M., Kang, D. J. & Hylemon, P. B. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47, 241\u2013259 (2006).","journal-title":"J. Lipid Res."},{"key":"1865_CR3","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","volume":"24","author":"A Wahlstr\u00f6m","year":"2016","unstructured":"Wahlstr\u00f6m, A., Sayin, S. I., Marschall, H. U. & B\u00e4ckhed, F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 24, 41\u201350 (2016).","journal-title":"Cell Metab."},{"key":"1865_CR4","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.molmed.2015.09.001","volume":"21","author":"S Fiorucci","year":"2015","unstructured":"Fiorucci, S. & Distrutti, E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol. Med. 21, 702\u2013714 (2015).","journal-title":"Trends Mol. Med."},{"key":"1865_CR5","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/ni.2640","volume":"14","author":"JR Brestoff","year":"2013","unstructured":"Brestoff, J. R. & Artis, D. Commensal bacteria at the interface of host metabolism and the immune system. Nat. Immunol. 14, 676\u2013684 (2013).","journal-title":"Nat. Immunol."},{"key":"1865_CR6","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nri.2016.36","volume":"16","author":"T Tanoue","year":"2016","unstructured":"Tanoue, T., Atarashi, K. & Honda, K. Development and maintenance of intestinal regulatory T cells. Nat. Rev. Immunol. 16, 295\u2013309 (2016).","journal-title":"Nat. Rev. Immunol."},{"key":"1865_CR7","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1146\/annurev-immunol-032712-095948","volume":"34","author":"M Panduro","year":"2016","unstructured":"Panduro, M., Benoist, C. & Mathis, D. Tissue Tregs. Annu. Rev. Immunol. 34, 609\u2013633 (2016).","journal-title":"Annu. Rev. Immunol."},{"key":"1865_CR8","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1126\/science.aaa9420","volume":"349","author":"E Sefik","year":"2015","unstructured":"Sefik, E. et al. Mucosal immunology. Individual intestinal symbionts induce a distinct population of ROR\u03b3+ regulatory T cells. Science 349, 993\u2013997 (2015).","journal-title":"Science"},{"key":"1865_CR9","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1126\/science.aac4263","volume":"349","author":"C Ohnmacht","year":"2015","unstructured":"Ohnmacht, C. et al. Mucosal immunology. The microbiota regulates type 2 immunity through ROR\u03b3t+ T cells. Science 349, 989\u2013993 (2015).","journal-title":"Science"},{"key":"1865_CR10","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1016\/j.cell.2017.01.022","volume":"168","author":"N Geva-Zatorsky","year":"2017","unstructured":"Geva-Zatorsky, N. et al. Mining the human gut microbiota for immunomodulatory organisms. Cell 168, 928\u2013943 (2017).","journal-title":"Cell"},{"key":"1865_CR11","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nature25500","volume":"554","author":"M Xu","year":"2018","unstructured":"Xu, M. et al. c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 554, 373\u2013377 (2018).","journal-title":"Nature"},{"key":"1865_CR12","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/j.cell.2017.02.009","volume":"168","author":"N Yissachar","year":"2017","unstructured":"Yissachar, N. et al. An intestinal organ culture system uncovers a role for the nervous system in microbe\u2013immune crosstalk. Cell 168, 1135\u20131148 (2017).","journal-title":"Cell"},{"key":"1865_CR13","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1126\/science.aac5560","volume":"351","author":"KS Kim","year":"2016","unstructured":"Kim, K. S. et al. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science 351, 858\u2013863 (2016).","journal-title":"Science"},{"key":"1865_CR14","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.cmet.2013.01.003","volume":"17","author":"SI Sayin","year":"2013","unstructured":"Sayin, S. I. et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17, 225\u2013235 (2013).","journal-title":"Cell Metab."},{"key":"1865_CR15","doi-asserted-by":"publisher","first-page":"e37182","DOI":"10.7554\/eLife.37182","volume":"7","author":"L Yao","year":"2018","unstructured":"Yao, L. et al. A selective gut bacterial bile salt hydrolase alters host metabolism. eLife 7, e37182 (2018).","journal-title":"eLife"},{"key":"1865_CR16","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/nchembio.1864","volume":"11","author":"AS Devlin","year":"2015","unstructured":"Devlin, A. S. & Fischbach, M. A. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat. Chem. Biol. 11, 685\u2013690 (2015).","journal-title":"Nat. Chem. Biol."},{"key":"1865_CR17","doi-asserted-by":"publisher","first-page":"17026","DOI":"10.1038\/nmicrobiol.2017.26","volume":"2","author":"AG Wexler","year":"2017","unstructured":"Wexler, A. G. & Goodman, A. L. An insider\u2019s perspective: Bacteroides as a window into the microbiome. Nat. Microbiol. 2, 17026 (2017).","journal-title":"Nat. Microbiol."},{"key":"1865_CR18","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.1128\/JB.172.8.4271-4279.1990","volume":"172","author":"AM Stevens","year":"1990","unstructured":"Stevens, A. M., Shoemaker, N. B. & Salyers, A. A. The region of a Bacteroides conjugal chromosomal tetracycline resistance element which is responsible for production of plasmidlike forms from unlinked chromosomal DNA might also be involved in transfer of the element. J. Bacteriol. 172, 4271\u20134279 (1990).","journal-title":"J. Bacteriol."},{"key":"1865_CR19","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1126\/science.1070477","volume":"296","author":"M Makishima","year":"2002","unstructured":"Makishima, M. et al. Vitamin D receptor as an intestinal bile acid sensor. Science 296, 1313\u20131316 (2002).","journal-title":"Science"},{"key":"1865_CR20","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1126\/science.284.5418.1362","volume":"284","author":"M Makishima","year":"1999","unstructured":"Makishima, M. et al. Identification of a nuclear receptor for bile acids. Science 284, 1362\u20131365 (1999).","journal-title":"Science"},{"key":"1865_CR21","doi-asserted-by":"publisher","first-page":"eaat5861","DOI":"10.1126\/sciimmunol.aat5861","volume":"3","author":"JR DiSpirito","year":"2018","unstructured":"DiSpirito, J. R. et al. Molecular diversification of regulatory T cells in nonlymphoid tissues. Sci. Immunol. 3, eaat5861 (2018).","journal-title":"Sci. Immunol."},{"key":"1865_CR22","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/mi.2015.74","volume":"9","author":"BH Yang","year":"2016","unstructured":"Yang, B. H. et al. Foxp3+ T cells expressing ROR\u03b3t represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. Mucosal Immunol. 9, 444\u2013457 (2016).","journal-title":"Mucosal Immunol."},{"key":"1865_CR23","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.immuni.2018.12.015","volume":"50","author":"GJ Britton","year":"2019","unstructured":"Britton, G. J. et al. Microbiotas from humans with inflammatory bowel disease alter the balance of gut Th17 and ROR\u03b3t+ regulatory T cells and exacerbate colitis in mice. Immunity 50, 212\u2013224 (2019).","journal-title":"Immunity"},{"key":"1865_CR24","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s00253-016-8006-6","volume":"101","author":"C Staley","year":"2017","unstructured":"Staley, C., Weingarden, A. R., Khoruts, A. & Sadowsky, M. J. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl. Microbiol. Biotechnol. 101, 47\u201364 (2017).","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"1865_CR25","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1002\/ibd.22966","volume":"19","author":"LN Xue","year":"2013","unstructured":"Xue, L. N. et al. Associations between vitamin D receptor polymorphisms and susceptibility to ulcerative colitis and Crohn\u2019s disease: a meta-analysis. Inflamm. Bowel Dis. 19, 54\u201360 (2013).","journal-title":"Inflamm. Bowel Dis."},{"key":"1865_CR26","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1161\/CIRCULATIONAHA.111.032680","volume":"124","author":"S Chen","year":"2011","unstructured":"Chen, S. et al. Cardiomyocyte-specific deletion of the vitamin D receptor gene results in cardiac hypertrophy. Circulation 124, 1838\u20131847 (2011).","journal-title":"Circulation"},{"key":"1865_CR27","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1194\/jlr.D600035-JLR200","volume":"48","author":"E Persson","year":"2007","unstructured":"Persson, E. et al. Simultaneous assessment of lipid classes and bile acids in human intestinal fluid by solid-phase extraction and HPLC methods. J. Lipid Res. 48, 242\u2013251 (2007).","journal-title":"J. Lipid Res."},{"key":"1865_CR28","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","volume":"3","author":"LW Sumner","year":"2007","unstructured":"Sumner, L. W. et al. Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics 3, 211\u2013221 (2007).","journal-title":"Metabolomics"},{"key":"1865_CR29","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.immuni.2015.06.024","volume":"43","author":"X Song","year":"2015","unstructured":"Song, X. et al. Growth factor FGF2 cooperates with interleukin-17 to repair intestinal epithelial damage. Immunity 43, 488\u2013501 (2015).","journal-title":"Immunity"},{"key":"1865_CR30","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nprot.2007.41","volume":"2","author":"S Wirtz","year":"2007","unstructured":"Wirtz, S., Neufert, C., Weigmann, B. & Neurath, M. F. Chemically induced mouse models of intestinal inflammation. Nat. Protocols 2, 541\u2013546 (2007).","journal-title":"Nat. Protocols"},{"key":"1865_CR31","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1126\/science.1198469","volume":"331","author":"K Atarashi","year":"2011","unstructured":"Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337\u2013341 (2011).","journal-title":"Science"},{"key":"1865_CR32","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/nature24489","volume":"551","author":"AL Haber","year":"2017","unstructured":"Haber, A. L. et al. A single-cell survey of the small intestinal epithelium. Nature 551, 333\u2013339 (2017).","journal-title":"Nature"},{"key":"1865_CR33","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nprot.2012.016","volume":"7","author":"C Trapnell","year":"2012","unstructured":"Trapnell, C. et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protocols 7, 562\u2013578 (2012).","journal-title":"Nat. Protocols"},{"key":"1865_CR34","doi-asserted-by":"publisher","first-page":"9831","DOI":"10.1073\/pnas.94.18.9831","volume":"94","author":"YC Li","year":"1997","unstructured":"Li, Y. C. et al. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc. Natl Acad. Sci. USA 94, 9831\u20139835 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1865-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1865-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1865-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T22:01:08Z","timestamp":1684620068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-019-1865-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,25]]},"references-count":34,"journal-issue":{"issue":"7790","published-print":{"date-parts":[[2020,1,16]]}},"alternative-id":["1865"],"URL":"https:\/\/doi.org\/10.1038\/s41586-019-1865-0","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,25]]},"assertion":[{"value":"15 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 December 2019","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"}}]}}