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The use of lytic bacteriophages could be a safe and effective approach to reduce <jats:italic>Salmonella<\/jats:italic> prevalence in poultry and subsequently the incidence in humans. This study examined the value of prophylactic phage treatment on <jats:italic>Salmonella<\/jats:italic> levels in chickens and the effect of such treatment on their overall gut microbiome. We also investigated phage persistence in vivo and resistance emergence against the six\u2010phage cocktail used. The preventive potential of phages was evaluated on 200 chicks by administering phages via drinking water for 6 days after hatching, followed by the <jats:italic>Salmonella<\/jats:italic> Enteritidis challenge on Day 7. The results showed that up to 4 days postinfection, phages had a preventive effect by significantly reducing <jats:italic>Salmonella<\/jats:italic> colonization in ceca by three logs. Furthermore, the phage cocktail did not induce dysbiosis, although variations in microbiota in terms of microbial composition were observed between conditions, with the Enterobacteriaceae family being impacted. However, the phage cocktail did not induce a long\u2010term effect, with <jats:italic>Salmonella<\/jats:italic> levels rebounding 8 days after phage treatment was stopped. Overall, our data show that phage prophylaxis can reduce <jats:italic>Salmonella<\/jats:italic> colonization and explore ways of improving the effectiveness of phages in limiting infections throughout poultry production.<\/jats:p>","DOI":"10.1002\/mbo3.70002","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T11:05:04Z","timestamp":1734347104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Prophylactic phage administration reduces <i>Salmonella<\/i> Enteritidis infection in newly hatched chicks"],"prefix":"10.1002","volume":"13","author":[{"given":"Lorna","family":"Agap\u00e9","sequence":"first","affiliation":[{"name":"INRAE, Universit\u00e9 de Tours, UMR ISP Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierrette","family":"Menanteau","sequence":"additional","affiliation":[{"name":"INRAE, Universit\u00e9 de Tours, UMR ISP Nouzilly 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