{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:24:12Z","timestamp":1793327052381,"version":"4.5.0"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>\n                    The emergence of multidrug bacterial isolates, including\n                    <jats:italic>Salmonella<\/jats:italic>\n                    (\n                    <jats:italic>S<\/jats:italic>\n                    .) Typhimurium, which primarily spreads to humans through chicken products, is correlated with a rising prevalence of antimicrobial therapy failure. Thus, we performed a comprehensive analysis of the combined impact of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    bacteriophage (BP) and grape seed oligomeric pro-anthocyanidins (GSOPs) on growth performance, immune functions, antioxidant capacity, cecal microbiota, gut integrity, and\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium resistance in challenged broilers. A total of 250 Ross-308 male broiler chicks were offered either a control diet or a diet supplemented with\n                    <jats:italic>Salmonella<\/jats:italic>\n                    BP alone at concentrations of 10\n                    <jats:sup>9<\/jats:sup>\n                    PFU\/0.1 ml, GSOPs alone at a level of 400 mg\/kg diet, and a combination of both\n                    <jats:italic>Salmonella<\/jats:italic>\n                    BP and GSOPs, and experimentally infected with multidrug-resistant (MDR)\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium strain at 14 days of age. Broilers administered BP, GSOPs, and their combination, particularly BP+GSOPs, had enhanced growth performance attributes even following a challenge with\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium, alongside decreased mortality percentage, which was evidenced by increased expression of\n                    <jats:italic>MUC-2<\/jats:italic>\n                    , \u03b2-defensin-1, cathelicidins-2,\n                    <jats:italic>JAM<\/jats:italic>\n                    -2, occludin, and\n                    <jats:italic>CLDN-1<\/jats:italic>\n                    genes, reduced\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium abundance, and downregulating its virulence-associated genes (\n                    <jats:italic>sopE<\/jats:italic>\n                    and\n                    <jats:italic>spvC<\/jats:italic>\n                    ), alongside restored intestinal histological features. GSOPs+BP fortified group exhibited higher cecal beneficial bacteria counts (\n                    <jats:italic>Bacteroides, Firmicutes, Lactobacillus<\/jats:italic>\n                    , and\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    species), lower cecal harmful bacteria loads (\n                    <jats:italic>Escherichia, Enterobacteriaceae<\/jats:italic>\n                    , and\n                    <jats:italic>Clostridium<\/jats:italic>\n                    clusters I and IV), decreased serum oxidative markers [H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , reactive oxygen species (ROS), and malondialdehyde (MDA)], and increased serum antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)]. The incorporation of dietary BP, and GSOPs combination significantly downregulated the intestinal inflammatory regulated genes (\n                    <jats:italic>IL-1<\/jats:italic>\n                    \u03b2\n                    <jats:italic>, IL-6, CCL4, CCL20, COX-2<\/jats:italic>\n                    , and\n                    <jats:italic>iNOS<\/jats:italic>\n                    ), and\n                    <jats:italic>mTOR<\/jats:italic>\n                    gene, and reduced the serum concentrations of LYZ, NO, CRP, and complement C3, alongside increased serum IgG, and IgM levels, and upregulation of autophagy-related genes (\n                    <jats:italic>atg5, atg7, atg12, BCLN-1<\/jats:italic>\n                    , and\n                    <jats:italic>LC3-II<\/jats:italic>\n                    ). The aforementioned beneficial effects of the BP and GSOPs combination support their prospective use in avian nutrition to enhance performance and stimulate immune defense against gastrointestinal illnesses, including\n                    <jats:italic>S<\/jats:italic>\n                    . Typhimurium infection.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2025.1694544","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T09:02:13Z","timestamp":1764147733000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel integrated approach modeling proanthocyanidins and bacteriophages to combat multidrug Salmonella Typhimurium in challenged broilers"],"prefix":"10.3389","volume":"12","author":[{"given":"Hanan S.","family":"Al-Khalaifah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abdelfattah-Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaaeldin","family":"Mohamed Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai. F.","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"El-Badry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reham A.","family":"Elbhnsawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa A.","family":"Azouz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayada","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherief M.","family":"Abdel-Raheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania M. 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