{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:46:14Z","timestamp":1788486374736,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Newly weaned animals are susceptible to a wide range of microbial infections taking a high risk of developing post-weaning diarrhea. Trained immunity is the capacity of the innate immune system to produce a stronger and non-specific response against a secondary infection after the inflammatory response caused by previous stimulus has returned to normal state. The objective of this study was to evaluate if the heat-inactivated <jats:italic>Escherichia coli<\/jats:italic> (IEC) as an immunostimulant on suckling pups elicits a protective effect on the intestine of post-weaning rats challenged with <jats:italic>Salmonella Typhimurium<\/jats:italic> (<jats:italic>S.Typhimurium<\/jats:italic>). We adapted a newborn rat model for this purpose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty newborn pups were randomly separated into two groups: IEC group (n =30) orally administrated IEC during suckling, while the CON group received orally the same dose of saline. Both of the two group challenged with various doses of <jats:italic>S.Typhimurium<\/jats:italic> after experiencing a 4-week resting period. Twelve of individuals were selected to detect the survival rate, and ten of the rest were necropsied 48 hours post-challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>The results showed that oral administration of IEC during suckling alleviated the injury in ileal morphology induced by post-weaning <jats:italic>S.Typhimurium<\/jats:italic> infection via increasing the levels of two tight junction proteins [zonula occluden-1 (ZO-1) and Occludin-1] and several secreted proteins (Lysozyme, Mucin-2, and SIgA) in the intestinal mucosa. Furthermore, the pre-stimulation with IEC significantly increased cytokines tumor necrosis factor-alpha (TNF- \u03b1) and interleukin-1 beta (IL-1 \u03b2) expressions in an enhanced secondary reaction way after experiencing a 4-week resting period. This implicated the possible involvement of trained immunity. The 16S rDNA sequence results showed that pre-stimulation with IEC decreased the abundance of <jats:italic>Clostridia, Prevotella, Christensenellaceae_R-7_group<\/jats:italic> and <jats:italic>Parabacteroides<\/jats:italic> after intestinal infection of <jats:italic>S.Typhimurium<\/jats:italic>. Our results confirmed that the previous oral administration of IEC had a protective effect on <jats:italic>S.Typhimurium<\/jats:italic>-induced intestinal injury in weaned rats by inducing a robust immune response. The present study suggested a new strategy for preventing intestinal infection of newborn animals.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1119747","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T13:17:31Z","timestamp":1680700651000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Oral administration of heat-inactivated Escherichia coli during suckling alleviated Salmonella typhimurium-derived intestinal injury after rat 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