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The aim of the current study was to examine the three-way interaction that occurred between host metabolites, resident gut microbiota and <jats:italic>Salmonella<\/jats:italic> following inoculation of SE in two-week-old layer chicks. Our results revealed an overall alteration in gut microbiome and metabolites in association with SE infection. Enriched colonization by different microbial members throughout the course of experimental infection highlighted significant fluctuation in the intestinal microbial community in response to <jats:italic>Salmonella<\/jats:italic> infection. As changes in community membership occurred, there was also subsequent impact on differential regulation of interlinked predicted functional activities within the intestinal environment dictated by <jats:italic>Salmonella<\/jats:italic>-commensal interaction. Alteration in the overall microbial community following infection also has a ripple effect on the host regulation of cecum-associated metabolic networks. The findings showed that there was differential regulation in many of the metabolites in association with SE colonization in chickens. Perturbation in metabolic pathways related to arginine and proline metabolism as well as TCA cycle was most prominently detected. Taken together, the present findings provided a starting point in understanding the effect of intestinal <jats:italic>Salmonella<\/jats:italic> carriage on the microbiome and metabolome of developing young layer chicks.<\/jats:p>","DOI":"10.1038\/s41598-020-60892-9","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T11:05:42Z","timestamp":1584356742000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Integrative analysis of gut microbiome and metabolites revealed novel mechanisms of intestinal Salmonella carriage in chicken"],"prefix":"10.1038","volume":"10","author":[{"given":"Khin K. 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