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Sodium butyrate (SB) has been shown to promote growth through enhanced intestinal health. This study investigated how broilers with different HW responded to in ovo SB injection and whether SB could enhance gut health and performance in LHW chicks. Ross 308 broiler eggs were injected on incubation d 12 with physiological saline (control) or SB at 0.1% (SB1), 0.3% (SB3), or 0.5% (SB5). Post-hatch, male chicks from each treatment were categorized as high HW (HHW) or LHW and assigned to 8 groups in a 4\u2009\u00d7\u20092 factorial design. Production parameters were recorded periodically. Intestinal weight, length, and gene expression related to gut barrier function and immune response were examined on d 14 and 42. Cecal microbiota dynamics and predicted functionality were analyzed using 16S rRNA gene sequencing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>SB treatments did not affect hatchability. HHW-control group exhibited consistently better weight gain and FCR than LHW-control group. SB dose-dependently influenced performance and gut health in both HW categories, with greater effects in LHW broilers at 0.3%. LHW-SB3 group attained highest body weight on d 42, exceeding controls but not significantly differing from HHW-SB3 group. LHW-SB3 group showed upregulation of gut-barrier genes <jats:italic>CLDN1<\/jats:italic> in ileum, <jats:italic>TJP1<\/jats:italic> in jejunum and anti-inflammatory cytokine <jats:italic>IL-10<\/jats:italic> in both jejunum and ileum on d 14. Additionally, LHW-SB3 group upregulated mucin-producing <jats:italic>MUC6<\/jats:italic> gene in ileum, while HHW-SB5 group increased pro-inflammatory <jats:italic>IL-12p40<\/jats:italic> cytokine in caecum on d 42. LHW-SB3 group demonstrated shorter relative intestinal lengths, while HHW-SB5 had longer lengths. HHW-control group had higher bacterial diversity and growth-promoting bacteria while LHW-control group harbored the potential pathogen <jats:italic>Helicobacter<\/jats:italic>. SB reshaped gut microbiota biodiversity, composition, and predicted metabolic pathways in both HW categories. The LHW-SB3 group exhibited highest alpha diversity on d 14 and most beneficial bacteria at all timepoints. HHW-SB5 group presented increased pathogenic <jats:italic>Escherichia-Shigella<\/jats:italic> and <jats:italic>Campylobacter<\/jats:italic> on d 42.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>HW significantly affects subsequent performance and SB has differential effects based on HW. LHW chicks benefited more from 0.3% SB, showing improvements in growth, intestinal development, health, and gut microbiota characteristics.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40104-024-01122-4","type":"journal-article","created":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:02:07Z","timestamp":1733529727000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In ovo sodium butyrate administration differentially impacts growth performance, intestinal barrier function, immune response, and gut microbiota characteristics in low and high hatch-weight broilers"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-3580","authenticated-orcid":false,"given":"Muhammad Zeeshan","family":"Akram","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Everaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Dunis\u0142awska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,7]]},"reference":[{"key":"1122_CR1","doi-asserted-by":"publisher","first-page":"699081","DOI":"10.3389\/fvets.2021.699081","volume":"8","author":"AH Nawaz","year":"2021","unstructured":"Nawaz AH, Amoah K, Leng QY, Zheng JH, Zhang WL, Zhang L. 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