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Because of the collateral damage antibiotics cause to the microbiota, microbiome-based interventions aimed at promoting decolonization have garnered interest. In this study, we evaluate the strain-specific potential of 430 commensal\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    isolates to inhibit the growth of an MDR\n                    <jats:italic>E. coli<\/jats:italic>\n                    strain. Comparative analyses using in vitro, ex vivo, and mouse models reveal that only a subset of commensal strains can facilitate gut decolonization. Bioinformatic and experimental analyses of the antagonism among representative strains demonstrate that both direct and indirect carbohydrate competition contribute to niche exclusion between\n                    <jats:italic>E. coli<\/jats:italic>\n                    strains. Finally, the combination of a protective\n                    <jats:italic>E. coli<\/jats:italic>\n                    strain with a\n                    <jats:italic>Klebsiella oxytoca<\/jats:italic>\n                    strain enhances the inhibitory potential against metabolically diverse MDR\n                    <jats:italic>E. coli<\/jats:italic>\n                    strains and additional MDR-E species, highlighting that rationally designed metabolically complementary approaches can contribute to developing next-generation probiotics with broad-spectrum activity.\n                  <\/jats:p>","DOI":"10.1038\/s41467-025-61327-7","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T03:52:04Z","timestamp":1751341924000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Suppression of gut colonization by multidrug-resistant Escherichia coli clinical isolates through cooperative niche exclusion"],"prefix":"10.1038","volume":"16","author":[{"given":"Marie","family":"Wende","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4862-650X","authenticated-orcid":false,"given":"Lisa","family":"Osbelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Eisenhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till Robin","family":"Lesker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bamu F.","family":"Damaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uthayakumar","family":"Mutukumarasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Bielecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-5478","authenticated-orcid":false,"given":"\u00c9va","family":"d. 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