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The consequences of early-life colonization on host development remain unknown. In a neonatal mouse model,\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    colonization drove proinflammatory and tissue repair responses in the intestinal epithelium, enriching injury-associated intestinal stem cell populations and skewing differentiation toward secretory lineages. Despite transient colonization, exposure to\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    early in life led to persistent changes into adulthood. Epithelial responses were toxin dependent, as colonization with nontoxigenic strains or maternal vaccination with a\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    \u2013targeted messenger RNA\u2013lipid nanoparticle vaccine protected neonates. Human infant intestinal epithelial cells were sensitive to\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    toxins, and biopsies from colonized infants exhibited altered intestinal stem cell behavior. This study redefines\n                    <jats:italic toggle=\"yes\">C. difficile<\/jats:italic>\n                    as an underappreciated early-life pathogen with lasting effects on host development.\n                  <\/jats:p>","DOI":"10.1126\/science.ady2886","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:00:43Z","timestamp":1788458443000},"page":"1045-1052","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Early-life colonization with\n                    <i>Clostridioides difficile<\/i>\n                    remodels the developing gut"],"prefix":"10.1126","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0551-1446","authenticated-orcid":true,"given":"Alexa","family":"Semon","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."},{"name":"Division of 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