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Hepatocytes synthesize primary BAs, which microbiota metabolize into secondary metabolites. Together, these species form a composite pool that circulates enterohepatically between the liver and intestines. Here, we show that immuno-regulatory outputs of the enterohepatic BA pool involve competition between multiple BA species for individual nuclear receptors and are dependent on intestinal health. In healthy mice, the primary BA, tauro-\u03b2-muricholic acid (t\u03b2MCA) antagonized ROR\u03b3t-mediated Th17 function in the presence of two secondary BAs (tDCA, tLCA) which activated ROR\u03b3t. Conversely, ileitis in Crohn\u2019s disease patients and\n                  <jats:italic>Tnf<\/jats:italic>\n                  <jats:sup>\u0394ARE\/+<\/jats:sup>\n                  mice depleted primary BAs by reducing the number and function of BA-transporting enterocytes. In mice, ileitis-driven t\u03b2MCA depletion enhanced tDCA\/tLCA-mediated ROR\u03b3t activation and supported Th17 cell function, whereas replenishing t\u03b2MCA in\n                  <jats:italic>Tnf<\/jats:italic>\n                  <jats:sup>\u0394ARE\/+<\/jats:sup>\n                  mice reestablished BA regulation of ileal Th17 cells. Thus, intra-pool competition underpins BA immunoregulatory functions and may reveal new opportunities for precision Crohn\u2019s disease therapy.\n                <\/jats:p>","DOI":"10.64898\/2026.09.13.751256","type":"posted-content","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:50:18Z","timestamp":1789797018000},"source":"Crossref","is-referenced-by-count":0,"title":["Ileitis abolishes tolerogenic functions of the enterohepatic bile acid pool"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0308-4759","authenticated-orcid":false,"given":"Zhiping","family":"Xiao","sequence":"first","affiliation":[{"name":"Walter and Carole Young Center for Digestive Health, Dartmouth Health, Lebanon, NH 03756, USA"},{"name":"Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH, 03755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4102-3850","authenticated-orcid":false,"given":"Koichi","family":"Sudo","sequence":"additional","affiliation":[{"name":"Walter and Carole Young Center for Digestive Health, Dartmouth Health, Lebanon, NH 03756, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8765-686X","authenticated-orcid":false,"given":"Amber","family":"Delmas-Eliason","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabao","family":"Liu","sequence":"additional","affiliation":[{"name":"Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Munoz-Tello","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Structural Biology, and Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3241-610X","authenticated-orcid":false,"given":"Henry D.","family":"Dionne","sequence":"additional","affiliation":[{"name":"Walter and Carole Young Center for Digestive Health, Dartmouth Health, Lebanon, NH 03756, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Structural Biology, and Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander D.","family":"Hondros","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Structural Biology, and Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH, 03755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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