{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:10:58Z","timestamp":1785870658702,"version":"3.56.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"857","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["183881"],"award-info":[{"award-number":["183881"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["RN279389"],"award-info":[{"award-number":["RN279389"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["35803"],"award-info":[{"award-number":["35803"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["203717"],"award-info":[{"award-number":["203717"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Discovery Grants Program","award":["ER22-17-067"],"award-info":[{"award-number":["ER22-17-067"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:p>\n                    Adherent-invasive\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    (AIEC) exhibits proinflammatory properties and has been implicated in the pathogenesis of Crohn\u2019s disease (CD), a form of inflammatory bowel disease (IBD). Antibiotic use in CD lacks specificity and may worsen microbiome disruption, prompting interest in bacteriophages (phages) for targeted microbiome editing. Here, we identified HER259, a phage active against clinical AIEC isolates. HER259 ameliorated colitis in gnotobiotic models and attenuated the virulence of AIEC strain NRG857c, including suppression of the FimH adhesin through inversion of the\n                    <jats:italic toggle=\"yes\">fimS<\/jats:italic>\n                    promoter to its \u201coff\u201d orientation. The effects were confirmed in CD-microbiota colitis models. Withdrawal of HER259 treatment led to reversion of the\n                    <jats:italic toggle=\"yes\">fimS<\/jats:italic>\n                    promoter and reactivated colitis. The HER259 phage also enhanced the therapeutic effect of subtherapeutic budesonide independent of microbial drug metabolism. These findings support targeted phage therapy as an adjunct treatment approach in IBD, demonstrating modulation of bacterial virulence and improved response to conventional treatments that may reduce drug-related side effects.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adz4589","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:58:12Z","timestamp":1783533492000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Phage intervention improves colitis and response to corticosteroids by attenuating virulence of Crohn\u2019s disease\u2013associated bacteria"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1824-3604","authenticated-orcid":true,"given":"Kyle","family":"Jackson","sequence":"first","affiliation":[{"name":"Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada."},{"name":"Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada."},{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6413-0803","authenticated-orcid":true,"given":"Heather J.","family":"Galipeau","sequence":"additional","affiliation":[{"name":"Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada."},{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Hann","sequence":"additional","affiliation":[{"name":"Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada."},{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7448-5552","authenticated-orcid":true,"given":"Marco","family":"Constante","sequence":"additional","affiliation":[{"name":"Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada."},{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0884-9936","authenticated-orcid":true,"given":"Megan T.","family":"Zangara","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; 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Sivignon, A. de Vall\u00e9e, D. Maura, C. Neut, O. Rahmouni, K. Wannerberger, A. Darfeuille-Michaud, P. Desreumaux, N. Barnich, L. Debarbieux, Bacteriophages targeting adherent invasive Escherichia coli strains as a promising new treatment for Crohn\u2019s disease. J. Crohns Colitis 11, 840\u2013847 (2017).","journal-title":"J. Crohns Colitis"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-55982-z"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","unstructured":"B. Chan G. Stanley K. Kortright M. Modak I. Ott Y. Sun S. W\u00fcrstle C. Grun B. Kazmierczak G. Rajagopalan Z. Harris C. Britto J. Stewart J. Talwalkar C. Appell N. Chaudary S. Jagpal R. Jain A. Kanu B. Quon J. Reynolds Q. Mai V. Shabanova P. Turner J. 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V. Lenth J. Piaskowski B. Banfai B. Bolker P. Buerkner I. Gin\u00e9-V\u00e1zquez M. Herv\u00e9 M. Jung J. Love F. Miguez H. Riebl H. Singmann emmeans: Estimated marginal means aka least square means. 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