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In our previous study, we found that the intestinal butyric acid level was significantly reduced in chronic stress models, suggesting that butyrate supplementation should be an effective anti-chronic stress strategy. Therefore, in this study, we aimed to investigate whether sodium butyrate (NaBu) prevents chronic stress-induced lipid metabolism disorders and intestinal injury by reducing intestinal damage and remodeling the microbiota. In vitro models, IEC-6 cells, a small intestinal epithelial cell line, were divided into three groups, including control (CON), corticosterone (CORT, 400\u00a0\u03bcM) and CORT\u2009+\u2009NaBu (400\u00a0\u03bcM CORT\u2009+\u20091\u00a0mM NaBu). In vivo models, sixty mice were divided into CON, CORT (intraperitoneal injection of 20\u00a0mg\/kg CORT) and CORT\u2009+\u2009NaBu (intraperitoneal injection of 20\u00a0mg\/kg CORT\u2009+\u2009intragastric gavage with 200\u00a0mg\/kg NaBu).\u00a0The results showed that NaBu effectively reversed CORT-induced IEC-6 migration inhibition, inhibited apoptosis, and restored barrier function, which was associated with downregulated IL-12 and upregulated LRP5 expression. In addition, NaBu administration prevented anorexia, promoted body weight gain, and improved lipid metabolism in a corticosterone-induced chronic stress model in mice, as evidenced by a significant reduction of serum alkaline phosphatase (AKP) and Low-density lipoprotein cholesterol (LDL-C). Histopathological staining and scanning electron microscopy analyses revealed that NaBu treatment restored the normal villi morphology of the small intestinal villi and mitigated epithelial cell damage caused by CORT. 16S rRNA sequencing demonstrated that NaBu facilitated intestinal microbiota remodeling, marked by significant increases in\n                    <jats:italic>Desulfobacterota<\/jats:italic>\n                    and\n                    <jats:italic>Bacillus<\/jats:italic>\n                    abundance and decreases in\n                    <jats:italic>Proteobacteria<\/jats:italic>\n                    and\n                    <jats:italic>Enterorhabdus<\/jats:italic>\n                    abundances. Furthermore, analysis suggests that CORT-induced chronic stress may disrupt the cecal microbiota-metabolite axis and lead to intestinal injury and metabolic abnormalitiesbased on previous metabolic evidence and current results of microbial imbalance and downstream metabolic\/intestinal abnormalities. These findings indicate that NaBu exerts a protective role in the prevention of chronic stress-related disorders, providing a potential prophylactic strategy for animals at high risk of stress exposure.\n                  <\/jats:p>","DOI":"10.1007\/s44154-026-00289-2","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:39:43Z","timestamp":1774845583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oral supplementation of sodium butyrate prevents lipid metabolism disorders and intestinal injury by modulating immunity, intestinal barrier functions, and gut microbiota in a corticosterone-induced chronic stress model in mice"],"prefix":"10.1007","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0194-7058","authenticated-orcid":false,"given":"Fei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4231-6551","authenticated-orcid":false,"given":"Lijun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-5076","authenticated-orcid":false,"given":"Ji","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-0708","authenticated-orcid":false,"given":"Shifeng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4419-3866","authenticated-orcid":false,"given":"Yao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"issue":"10","key":"289_CR1","doi-asserted-by":"publisher","first-page":"104108","DOI":"10.1016\/j.psj.2024.104108","volume":"103","author":"A Be\u0142dowska","year":"2024","unstructured":"Be\u0142dowska A, Pietrzak E, Biesek J, Barszcz M, Tu\u015bnio A, Konopka A, Gawin K, Dunis\u0142awska A\u00a0(2024) The effect of sodium butyrate administered in ovo on the health status and intestinal response in broiler chicken. 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