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Here, we show that dextran sulfate sodium (DSS)\u2013induced colitis severity correlates with compensatory GLP-1 increases, while receptor blockade worsens damage, confirming GLP-1\u2019s protective role during colitis. Fiber deficiency impaired L cell function and GLP-1 release, increasing colitis susceptibility. GLP-1 receptor agonist reversed these effects, restoring barrier integrity and accelerating recovery. We engineered a probiotic, releasing a microbial peptide, that locally elevates GLP-1, which normalized gut parameters in fiber-deprived mice and alleviated colitis via GLP-1\u2013dependent mechanisms, including improved metabolism, antimicrobial defenses , and barrier restoration. Our findings mechanistically connect fiber deficiency to colitis through GLP-1 and demonstrate that probiotic-mediated GLP-1 modulation can bypass dietary fiber requirements to maintain gut homeostasis.<\/jats:p>","DOI":"10.1126\/sciadv.adx6869","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:58:33Z","timestamp":1762541913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Engineered probiotic restores GLP-1 signaling to ameliorate fiber-deficiency exacerbated colitis"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7789-7616","authenticated-orcid":true,"given":"Leonie","family":"Brockmann","sequence":"first","affiliation":[{"name":"Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA."},{"name":"Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo 108-8345, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7501-914X","authenticated-orcid":true,"given":"Carlotta","family":"Ronda","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA."},{"name":"Innovative Genomics Institute at UC Berkley, Berkley, CA 94720, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan T.","family":"Schwanz","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5327-8198","authenticated-orcid":true,"given":"Yiming","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA."},{"name":"Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1602-1787","authenticated-orcid":true,"given":"Daniel W.","family":"Shneider","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3914-7512","authenticated-orcid":true,"given":"Chrystal F.","family":"Mavros","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA."},{"name":"Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, 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