{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:07:37Z","timestamp":1789024057811,"version":"build-2803163510"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"52","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100023581","name":"NSF | NSF Graduate Research Fellowship Program","doi-asserted-by":"publisher","award":["DGE2139757"],"award-info":[{"award-number":["DGE2139757"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"NSF | NSF Graduate Research Fellowship Program","doi-asserted-by":"publisher","award":["DGE1746891"],"award-info":[{"award-number":["DGE1746891"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["K99AG081564"],"award-info":[{"award-number":["K99AG081564"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,12,30]]},"abstract":"<jats:p>\n                    Therapeutic biological scaffolds promote tissue repair primarily through the induction of type 2 immunity. However, systemic immunological factors, including aging, sex, and previous infections, can modulate this response. The gut microbiota is a well-established modulator of immune function across organ systems, yet its influence on type 2-mediated repair remains underexplored. Here, we establish a bidirectional relationship between the gut microbiota and biological scaffold-mediated tissue repair. Utilizing a conventionalized germ-free mouse, we demonstrate that scaffold implantation induces compositional and functional changes in the gut microbiome, particularly affecting amino acid biosynthesis. Additionally, in a model of antibiotic-induced microbiota depletion, we show that dysbiosis disrupts key immune regulators of type 2 immunity, including reductions in eosinophils, proregenerative macrophages, and interleukin-4 (IL-4)-producing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. At 6 wk post\u2013scaffold implantation, we observed a significant decrease in myocytes with centrally located nuclei alongside an upregulation in profibrotic gene expression with antibiotic treatment. These findings provide insights into the influence of the gut microbiota on type 2-mediated tissue repair.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2510841122","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T20:00:56Z","timestamp":1766433656000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Antibiotic-induced microbiota depletion impairs the proregenerative response to a biological scaffold"],"prefix":"10.1073","volume":"122","author":[{"given":"Natalie","family":"Rutkowski","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, 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Rutkowski B. Yang M. Patatanian C. Cherry Antibiotic-induced microbiota depletion impairs the pro-regenerative response to a biological scaffold. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE312555. 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