{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:46:56Z","timestamp":1782150416936,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,19]]},"group-title":"Immunology","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R01AI177704-01A1"],"award-info":[{"award-number":["R01AI177704-01A1"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R21AG079550"],"award-info":[{"award-number":["R21AG079550"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006418","name":"Brown University","doi-asserted-by":"crossref","award":["Seed grant"],"award-info":[{"award-number":["Seed grant"]}],"id":[{"id":"10.13039\/100006418","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014082","name":"Rhode Island Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014082","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Searle Scholar's program"},{"DOI":"10.13039\/100002570","name":"American Association of Immunologists","doi-asserted-by":"crossref","award":["Careers in Immunology Fellowship"],"award-info":[{"award-number":["Careers in Immunology Fellowship"]}],"id":[{"id":"10.13039\/100002570","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Laboratory-raised specific pathogen-free (SPF) mice have been indispensable for fundamental immunology research, yet their reliability in predicting human clinical outcomes has been questionable. A major factor contributing to this disconnect is the sanitized housing environment, which deprives laboratory mice of physiological microbial exposure critical for immune maturation. Various approaches have been developed to introduce microbes to SPF mice, aiming to mimic human-like microbial experiences and engender adult human-like immune traits. However, some of these methods, specifically the pet store mice cohousing approach suffer from significant variability in pathogen exposure driven by the uncontrolled nature of microbial exchange and is associated with heightened mortality. Here we present an alternative gavage-fomite (GaF) method that exposes mice to a similarly diverse array of pathogens and commensal as the pet store cohousing method while limiting mortality. GaF-treated mice exhibited consistent gut microbial composition, robust immune maturation characterized by mucosal T-cell distribution, elevated serum inflammatory cytokines, and a splenic immune transcriptional signature closely aligned with that of adult humans. Furthermore, these mice demonstrated enhanced protection against a virulent bacterial challenge. The simplicity, and effectiveness of the GaF method for generating \u2018mice with natural microbiota,\u2019 may support broader use of these models in basic and translational immunological research across institutions.<\/jats:p>","DOI":"10.64898\/2026.06.15.732393","type":"posted-content","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T23:10:10Z","timestamp":1781910610000},"source":"Crossref","is-referenced-by-count":0,"title":["A gavage-fomite based method to generate mouse models with natural microbiota"],"prefix":"10.64898","author":[{"given":"Geongoo","family":"Han","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad H.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olumide","family":"Adesioye","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Pacia","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian C.","family":"Ramprashad","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio","family":"Valdez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shipra","family":"Vaishnava","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalit K.","family":"Beura","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026062209550848000_2026.06.15.732393v1.1","doi-asserted-by":"crossref","unstructured":"Rehermann, B. , A. L. Graham , D. Masopust , and S. E. Hamilton . 2024. Integrating natural commensals and pathogens into preclinical mouse models. Nat. Rev. Immunol. 1\u201313.","DOI":"10.1038\/s41577-024-01108-3"},{"key":"2026062209550848000_2026.06.15.732393v1.2","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.chom.2020.02.015","article-title":"Altered Immunity of Laboratory Mice in the Natural Environment Is Associated with Fungal Colonization","volume":"27","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2026062209550848000_2026.06.15.732393v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.add6910"},{"key":"2026062209550848000_2026.06.15.732393v1.4","doi-asserted-by":"crossref","unstructured":"Arnesen, H. , L. E. Knutsen , B. W. Hognestad , G. M. Johansen , M. Bemark , O. Pabst , A. K. Storset , and P. Boysen . 2021. A Model System for Feralizing Laboratory Mice in Large Farmyard-Like Pens. Front. 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