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Engineered cell-based biosensors can tap into this molecular information and report on their environment, yet their development in gut-resident symbionts has been limited by a lack of validated sensor systems. Here, we present a generalizable pipeline that leverages bacterial transcriptional profiling to identify environment-responsive systems for biosensor engineering. Candidate Sensors Systems (CSSs) mined from healthy, disease, and\n                  <jats:italic>in vitro<\/jats:italic>\n                  transcriptomes were assembled into a barcoded library in Bacteroidaceae chassis and screened in high-throughput\n                  <jats:italic>in vivo<\/jats:italic>\n                  to identify responsive promoters. A unique Bacteroidales ECF-type sigma factor operon with ties to sphingolipid metabolism and flux was highly responsive in chemically-induced colitis models. The biosensor responded robustly to disease and returned to baseline upon recovery, establishing an\n                  <jats:italic>in vivo<\/jats:italic>\n                  -driven strategy for discovering functional biosensors in non-model gut-resident bacteria.\n                <\/jats:p>","DOI":"10.64898\/2026.08.10.744002","type":"posted-content","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:05:31Z","timestamp":1786460731000},"source":"Crossref","is-referenced-by-count":0,"title":["Mining Microbial Transcriptomes to Engineer Cell-Based Bacterial Biosensors in Gut-Resident Bacteroidaceae"],"prefix":"10.64898","author":[{"given":"Joshua","family":"Glazier","sequence":"first","affiliation":[{"name":"Pritzker School of Molecular Engineering, University of Chicago, 5640 S Ellis Ave, Chicago, 60637, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Villegas","sequence":"additional","affiliation":[{"name":"Committee on Microbiology, University of Chicago, 924 E. 57th Street, BSLC R013A, Chicago, 60637, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"McClure","sequence":"additional","affiliation":[{"name":"Committee on Molecular Metabolism and Nutrition, University of Chicago, 924 E. 57th Street, BSLC R013A, Chicago, 60637, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Ghali","sequence":"additional","affiliation":[{"name":"Committee on Molecular Metabolism and Nutrition, University of Chicago, 924 E. 57th Street, BSLC R013A, Chicago, 60637, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Fuerte-Stone","sequence":"additional","affiliation":[{"name":"Committee on Microbiology, University of Chicago, 924 E. 57th Street, BSLC R013A, Chicago, 60637, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3083-2671","authenticated-orcid":false,"given":"Mark","family":"Mimee","sequence":"additional","affiliation":[{"name":"Pritzker School of Molecular Engineering, University of Chicago, 5640 S Ellis Ave, Chicago, 60637, IL, USA"},{"name":"Committee on Microbiology, University of Chicago, 924 E. 57th Street, BSLC R013A, Chicago, 60637, IL, USA"},{"name":"Committee on Molecular Metabolism and Nutrition, University of Chicago, 924 E. 57th Street, BSLC R013A, Chicago, 60637, IL, USA"},{"name":"Department of Microbiology, University of Chicago, 920 E 58th Street, Chicago, 60637, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081304001307000_2026.08.10.744002v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23889"},{"key":"2026081304001307000_2026.08.10.744002v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.10.043"},{"key":"2026081304001307000_2026.08.10.744002v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2016.40"},{"key":"2026081304001307000_2026.08.10.744002v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.01.003"},{"key":"2026081304001307000_2026.08.10.744002v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1237-9"},{"key":"2026081304001307000_2026.08.10.744002v1.6","first-page":"293","article-title":"Gut microbiome structure and metabolic activity in inflammatory bowel disease","volume":"4","year":"2019","journal-title":"Nature Microbiology"},{"key":"2026081304001307000_2026.08.10.744002v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2008.00145.x"},{"key":"2026081304001307000_2026.08.10.744002v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.103"},{"key":"2026081304001307000_2026.08.10.744002v1.9","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.55.3.371-394.1991"},{"key":"2026081304001307000_2026.08.10.744002v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2000.tb09413.x"},{"key":"2026081304001307000_2026.08.10.744002v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/35002131"},{"key":"2026081304001307000_2026.08.10.744002v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/35002125"},{"key":"2026081304001307000_2026.08.10.744002v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm6038"},{"key":"2026081304001307000_2026.08.10.744002v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4222"},{"key":"2026081304001307000_2026.08.10.744002v1.15","doi-asserted-by":"crossref","unstructured":"Hwang, I.Y . 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