{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T20:29:08Z","timestamp":1787084948819,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,15]]},"group-title":"Immunology","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R21AI186046"],"award-info":[{"award-number":["R21AI186046"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35GM147478"],"award-info":[{"award-number":["R35GM147478"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["GRF DGE 1746045"],"award-info":[{"award-number":["GRF DGE 1746045"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Modern lifestyle factors have altered gut microbiota composition and function. Bacteria in the Clostridia class modulate mucosal immune responses through various mechanisms including production of secondary bile acids (SBA). Here, we present a novel system to study how the SBA isodeoxycholic acid (isoDCA) regulates host immunity. Through targeted mutagenesis of bile acid epimerization genes, we engineered\n                  <jats:italic>Ruminococcus gnavus<\/jats:italic>\n                  to ablate isoDCA production. Combining\n                  <jats:italic>R. gnavus<\/jats:italic>\n                  (WT or KO) with\n                  <jats:italic>Peptacetobacter hiranonis<\/jats:italic>\n                  created a two-member consortium that toggles isoDCA production on or off while keeping all other variables constant. Using this system, we demonstrate that isoDCA induces colonic lamina propria ROR\u03b3t\u25a1 Foxp3\u25a1 regulatory T cells (pTregs) through a mechanism requiring both the Takeda G protein-coupled receptor 5 (TGR5) and the Farnesoid X receptor (FXR). Engraftment of this isoDCA+ consortium protected against colitis in an adoptive T cell transfer model by reshaping the microbiota and suppressing host inflammation.\n                <\/jats:p>","DOI":"10.64898\/2026.08.11.743107","type":"posted-content","created":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T04:10:11Z","timestamp":1786853411000},"source":"Crossref","is-referenced-by-count":0,"title":["An engineered Clostridial mini consortium modulates intestinal inflammation"],"prefix":"10.64898","author":[{"given":"Edward","family":"Ionescu","sequence":"first","affiliation":[{"name":"Pritzker School of Molecular Engineering, The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack H.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Pritzker School of Molecular Engineering, The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Weber","sequence":"additional","affiliation":[{"name":"Departments of Pathology, The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mimee","sequence":"additional","affiliation":[{"name":"Pritzker School of Molecular Engineering, The University of Chicago, Chicago, Illinois, USA"},{"name":"Microbiology, The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7254-6617","authenticated-orcid":false,"given":"Cathryn R.","family":"Nagler","sequence":"additional","affiliation":[{"name":"Pritzker School of Molecular Engineering, The University of Chicago, Chicago, Illinois, USA"},{"name":"Departments of Pathology, The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081812550982000_2026.08.11.743107v1.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042718-041621"},{"key":"2026081812550982000_2026.08.11.743107v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw9255"},{"key":"2026081812550982000_2026.08.11.743107v1.3","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13396"},{"key":"2026081812550982000_2026.08.11.743107v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.002"},{"key":"2026081812550982000_2026.08.11.743107v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.02.013"},{"key":"2026081812550982000_2026.08.11.743107v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00667-9"},{"key":"2026081812550982000_2026.08.11.743107v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.03.002"},{"key":"2026081812550982000_2026.08.11.743107v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412008111"},{"key":"2026081812550982000_2026.08.11.743107v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0324-z"},{"key":"2026081812550982000_2026.08.11.743107v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-022-00972-5"},{"key":"2026081812550982000_2026.08.11.743107v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2024.05.019"},{"key":"2026081812550982000_2026.08.11.743107v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113153"},{"key":"2026081812550982000_2026.08.11.743107v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00805-x"},{"key":"2026081812550982000_2026.08.11.743107v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00566-7"},{"key":"2026081812550982000_2026.08.11.743107v1.15","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R500013-JLR200"},{"key":"2026081812550982000_2026.08.11.743107v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2019.07.012"},{"key":"2026081812550982000_2026.08.11.743107v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.02.004"},{"key":"2026081812550982000_2026.08.11.743107v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2025.12.008"},{"key":"2026081812550982000_2026.08.11.743107v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2396-4"},{"key":"2026081812550982000_2026.08.11.743107v1.20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00027.2007"},{"key":"2026081812550982000_2026.08.11.743107v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2193-0"},{"key":"2026081812550982000_2026.08.11.743107v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1785-z"},{"key":"2026081812550982000_2026.08.11.743107v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.07.013"},{"key":"2026081812550982000_2026.08.11.743107v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1864"},{"key":"2026081812550982000_2026.08.11.743107v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.035"},{"key":"2026081812550982000_2026.08.11.743107v1.26","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.216"},{"key":"2026081812550982000_2026.08.11.743107v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2016.05.011"},{"key":"2026081812550982000_2026.08.11.743107v1.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1820256116"},{"key":"2026081812550982000_2026.08.11.743107v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2009.10.018"},{"key":"2026081812550982000_2026.08.11.743107v1.30","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav1282"},{"key":"2026081812550982000_2026.08.11.743107v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-69022-x"},{"key":"2026081812550982000_2026.08.11.743107v1.32","doi-asserted-by":"publisher","DOI":"10.1101\/2025.11.08.687059"},{"key":"2026081812550982000_2026.08.11.743107v1.33","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.66.3.1107-1113.2000"},{"key":"2026081812550982000_2026.08.11.743107v1.34","doi-asserted-by":"publisher","DOI":"10.1128\/aem.63.3.1185-1188.1997"},{"key":"2026081812550982000_2026.08.11.743107v1.35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1999.tb01224.x"},{"key":"2026081812550982000_2026.08.11.743107v1.36","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2018.1549420"},{"key":"2026081812550982000_2026.08.11.743107v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.002"},{"key":"2026081812550982000_2026.08.11.743107v1.38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.6978"},{"key":"2026081812550982000_2026.08.11.743107v1.39","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00006-09"},{"key":"2026081812550982000_2026.08.11.743107v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.047"},{"key":"2026081812550982000_2026.08.11.743107v1.41","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.28403"},{"key":"2026081812550982000_2026.08.11.743107v1.42","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00707-24"},{"key":"2026081812550982000_2026.08.11.743107v1.43","doi-asserted-by":"publisher","DOI":"10.1186\/2049-2618-2-15"},{"key":"2026081812550982000_2026.08.11.743107v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.11.006"},{"key":"2026081812550982000_2026.08.11.743107v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117731"},{"key":"2026081812550982000_2026.08.11.743107v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-025-00202-w"},{"key":"2026081812550982000_2026.08.11.743107v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1865-0"},{"key":"2026081812550982000_2026.08.11.743107v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2021.12.006"},{"key":"2026081812550982000_2026.08.11.743107v1.49","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/5.11.1461"},{"key":"2026081812550982000_2026.08.11.743107v1.50","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.1092"},{"key":"2026081812550982000_2026.08.11.743107v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.74"},{"key":"2026081812550982000_2026.08.11.743107v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.12.015"},{"key":"2026081812550982000_2026.08.11.743107v1.53","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa9420"},{"key":"2026081812550982000_2026.08.11.743107v1.54","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4263"},{"key":"2026081812550982000_2026.08.11.743107v1.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922189117"},{"key":"2026081812550982000_2026.08.11.743107v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0461-z"},{"key":"2026081812550982000_2026.08.11.743107v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56449-x"},{"key":"2026081812550982000_2026.08.11.743107v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-024-00896-2"},{"key":"2026081812550982000_2026.08.11.743107v1.59","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2015.1127483"},{"key":"2026081812550982000_2026.08.11.743107v1.60","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2019.1618173"},{"key":"2026081812550982000_2026.08.11.743107v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.05.037"},{"key":"2026081812550982000_2026.08.11.743107v1.62","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00455-22"},{"key":"2026081812550982000_2026.08.11.743107v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90045-0"},{"key":"2026081812550982000_2026.08.11.743107v1.64","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061082"},{"key":"2026081812550982000_2026.08.11.743107v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.08.010"},{"key":"2026081812550982000_2026.08.11.743107v1.66","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0337727"},{"key":"2026081812550982000_2026.08.11.743107v1.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2003.12.009"},{"key":"2026081812550982000_2026.08.11.743107v1.68","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"2026081812550982000_2026.08.11.743107v1.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2019.06.008"},{"key":"2026081812550982000_2026.08.11.743107v1.70","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.295"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.08.11.743107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T19:55:20Z","timestamp":1787082920000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.08.11.743107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,15]]},"references-count":70,"URL":"https:\/\/doi.org\/10.64898\/2026.08.11.743107","relation":{},"subject":[],"published":{"date-parts":[[2026,8,15]]},"subtype":"preprint"}}