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Enteritidis<\/jats:italic> infection in broilers is a main foodborne illness that substantially threatens food security. This study aimed to examine the effects of a novel polysaccharide isolated from alfalfa (APS) on the intestinal microbiome and systemic health of <jats:italic>S. ser. Enteritidis-<\/jats:italic>infected broilers. The results indicated that broilers receiving the APS-supplemented diet had the improved (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) growth performance and gut health than those fed no APS-supplemented diet. Supplementation with APS enhanced (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) the richness of gut beneficial microbes such as <jats:italic>Bacteroidetes<\/jats:italic>, <jats:italic>Barnesiella<\/jats:italic>, <jats:italic>Parabacteroides<\/jats:italic>, <jats:italic>Butyricimonas<\/jats:italic>, and <jats:italic>Prevotellaceae<\/jats:italic>, while decreased (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) the abundance of facultative anaerobic bacteria including <jats:italic>Proteobacteri<\/jats:italic>a, <jats:italic>Actinobacteria<\/jats:italic>, <jats:italic>Ruminococcaceae<\/jats:italic>, <jats:italic>Lachnospiraceae<\/jats:italic>, and <jats:italic>Burkholderiaceae<\/jats:italic> in the <jats:italic>S. ser. Enteritidis<\/jats:italic>-infected broilers. The <jats:italic>Bacteroides<\/jats:italic> and <jats:italic>Odoribacter<\/jats:italic> were identified as the two core microbes across all treatments and combined with their syntrophic microbes formed the hub in co-occurrence networks linking microbiome structure to performance of broilers. Taken together, dietary APS supplementation improved the systemic health of broilers by reshaping the intestinal microbiome regardless of whether <jats:italic>S. ser. Enteritidis<\/jats:italic> infection was present. Therefore, APS can be employed as a potential functional additives to inhibit the <jats:italic>S. ser. 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