{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:02:17Z","timestamp":1779919337281,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,25]]},"group-title":"Microbiology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The bile acid pool, which is synthesized collaboratively by the host and its microbiome, impacts metabolism, immunity, and disease risk. Targeted microbiome interventions could in principle reshape the bile acid pool for therapeutic benefit, but practical strategies remain elusive. In the course of screening a complex defined community for metabolic phenotypes by dropping out individual strains, we observed that several of the single-strain dropout communities had markedly increased deoxycholic and lithocholic acid levels and a larger bile acid pool. In each of these communities, a second strain\u2014\n                  <jats:italic>Lactobacillus plantarum\u2014<\/jats:italic>\n                  had bloomed. The bile salt hydrolase activity of\n                  <jats:italic>L. plantarum<\/jats:italic>\n                  was necessary and sufficient to expand the size of the bile acid pool. An engineered community in which the\n                  <jats:italic>bsh<\/jats:italic>\n                  gene is overexpressed in multiple\n                  <jats:italic>Lactobacillus<\/jats:italic>\n                  strains confers on mice increased levels of secondary bile acid levels and a larger pool size. By overexpressing a different pair of bile acid metabolic genes in multiple strains of\n                  <jats:italic>Lactobacillus<\/jats:italic>\n                  \u20147\u03b1- and 7\u03b2-hydroxysteroid dehydrogenase\u2014we changed the composition of the bile acid pool, enlarging it and redirecting it toward ursodeoxycholic acid. Together, these results demonstrate that fine details of the microbiome\u2019s strain composition can have a substantial effect on bile acid metabolism, and that rational manipulation of the microbiome can alter the size and composition of the bile acid pool.\n                <\/jats:p>","DOI":"10.64898\/2026.05.23.727444","type":"posted-content","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T17:20:31Z","timestamp":1779729631000},"source":"Crossref","is-referenced-by-count":0,"title":["Ecology and engineering to modify the bile acid output of a defined microbial community"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-3388","authenticated-orcid":false,"given":"Xianfeng","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA"},{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiandong","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA"},{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6694-6964","authenticated-orcid":false,"given":"Allison M.","family":"Weakley","sequence":"additional","affiliation":[{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5358-8280","authenticated-orcid":false,"given":"Kelsey E.","family":"Jarrett","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Higginbottom","sequence":"additional","affiliation":[{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenell Mae","family":"Lopez","sequence":"additional","affiliation":[{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley V.","family":"Cabrera","sequence":"additional","affiliation":[{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"DeFelice","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Terasaki","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA"},{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochelle","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelaine","family":"Brearley-Sholto","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-7981","authenticated-orcid":false,"given":"Aishan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA"},{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerrigan R.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA"},{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Levia","sequence":"additional","affiliation":[{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Arreola","sequence":"additional","affiliation":[{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Q.","family":"de Aguiar Vallim","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3079-8247","authenticated-orcid":false,"given":"Michael A.","family":"Fischbach","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA 94305, USA"},{"name":"ChEM-H Institute, Stanford University, Stanford, CA 94305, USA"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052714051421000_2026.05.23.727444v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-7568-6"},{"key":"2026052714051421000_2026.05.23.727444v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2013.tb00517.x"},{"key":"2026052714051421000_2026.05.23.727444v1.3","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.804"},{"key":"2026052714051421000_2026.05.23.727444v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2396-4"},{"key":"2026052714051421000_2026.05.23.727444v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.019"},{"key":"2026052714051421000_2026.05.23.727444v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1864"},{"key":"2026052714051421000_2026.05.23.727444v1.7","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.37182"},{"key":"2026052714051421000_2026.05.23.727444v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.07.017"},{"key":"2026052714051421000_2026.05.23.727444v1.9","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R500013-JLR200"},{"key":"2026052714051421000_2026.05.23.727444v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06990-w"},{"key":"2026052714051421000_2026.05.23.727444v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2047-9"},{"key":"2026052714051421000_2026.05.23.727444v1.12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI105892"},{"key":"2026052714051421000_2026.05.23.727444v1.13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.18.020167.002001"},{"key":"2026052714051421000_2026.05.23.727444v1.14","doi-asserted-by":"publisher","DOI":"10.1152\/physiologyonline.1999.14.1.24"},{"key":"2026052714051421000_2026.05.23.727444v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.11.010"},{"key":"2026052714051421000_2026.05.23.727444v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2193-0"},{"key":"2026052714051421000_2026.05.23.727444v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03832-5"},{"key":"2026052714051421000_2026.05.23.727444v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2013.10.021"},{"key":"2026052714051421000_2026.05.23.727444v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30300-3"},{"key":"2026052714051421000_2026.05.23.727444v1.20","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31652"},{"key":"2026052714051421000_2026.05.23.727444v1.21","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0028"},{"key":"2026052714051421000_2026.05.23.727444v1.22","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3776-8"},{"key":"2026052714051421000_2026.05.23.727444v1.23","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29359"},{"key":"2026052714051421000_2026.05.23.727444v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2025.02.031"},{"key":"2026052714051421000_2026.05.23.727444v1.25","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2023.2293814"},{"key":"2026052714051421000_2026.05.23.727444v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.01.021"},{"key":"2026052714051421000_2026.05.23.727444v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nature13828"},{"key":"2026052714051421000_2026.05.23.727444v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)33041-7"},{"key":"2026052714051421000_2026.05.23.727444v1.29","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-015-0500-2"},{"key":"2026052714051421000_2026.05.23.727444v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.06.012"},{"key":"2026052714051421000_2026.05.23.727444v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.05.037"},{"key":"2026052714051421000_2026.05.23.727444v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.035"},{"key":"2026052714051421000_2026.05.23.727444v1.33","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00137-08"},{"key":"2026052714051421000_2026.05.23.727444v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4633"},{"key":"2026052714051421000_2026.05.23.727444v1.35","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M071183"},{"key":"2026052714051421000_2026.05.23.727444v1.36","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.RA119000395"},{"key":"2026052714051421000_2026.05.23.727444v1.37","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.RA119000243"},{"key":"2026052714051421000_2026.05.23.727444v1.38","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001438"},{"key":"2026052714051421000_2026.05.23.727444v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.06.050"},{"key":"2026052714051421000_2026.05.23.727444v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/nature18849"},{"key":"2026052714051421000_2026.05.23.727444v1.41","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1924-7_42"},{"key":"2026052714051421000_2026.05.23.727444v1.42","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.311221"},{"key":"2026052714051421000_2026.05.23.727444v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.11.009"},{"key":"2026052714051421000_2026.05.23.727444v1.44","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-369-5_13"},{"key":"2026052714051421000_2026.05.23.727444v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-020-00710-5"},{"key":"2026052714051421000_2026.05.23.727444v1.46","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-024-02302-7"},{"key":"2026052714051421000_2026.05.23.727444v1.47","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku623"},{"key":"2026052714051421000_2026.05.23.727444v1.48","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201800690"},{"key":"2026052714051421000_2026.05.23.727444v1.49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2414342122"},{"key":"2026052714051421000_2026.05.23.727444v1.50","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02502-08"},{"key":"2026052714051421000_2026.05.23.727444v1.51","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00137-08"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.23.727444","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:05:23Z","timestamp":1779915923000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.23.727444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":51,"URL":"https:\/\/doi.org\/10.64898\/2026.05.23.727444","relation":{},"subject":[],"published":{"date-parts":[[2026,5,25]]},"subtype":"preprint"}}