Butyrate combined with niacin promotes colonic metabolism and antimicrobial peptide expression to alleviate ETEC-induced colonic barrier dysfunction in weaned piglets

Butyrate combined with niacin promotes colonic metabolism and antimicrobial peptide expression to alleviate ETEC-induced colonic barrier dysfunction in weaned piglets | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Butyrate combined with niacin promotes colonic metabolism and antimicrobial peptide expression to alleviate ETEC-induced colonic barrier dysfunction in weaned piglets Qingsong Tang, Rui Zhen, Bijing Yang, Zhenyan Miao, Yangyang Wei, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8061761/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background Butyrate is the primary energy substrate in the colon, whereas niacin can enhance energy metabolic flux by increasing nicotinamide adenine dinucleotide (NAD) synthesis. Therefore, this study aimed to investigate the effects of combining butyrate with niacin on colonic metabolism and resistance to enterotoxigenic Escherichia coli (ETEC) infection in weaned piglets. In this study, two animal experiments were designed to observe the optimal butyrate-to-niacin ratio and assess their responses to the ETEC challenge. Results Supplementation with Butyrate and niacin at a ratio of 100:2 (2000 mg/kg butyrate and 40 mg/kg niacin, BN2) increased the average daily gain (ADG) and reduced the diarrhea incidence. We also observed an increase in the levels of NAD in the colon of weaned piglets. Notably, BN2 promoted amino acid anabolism in the colon and enhanced glycolysis and the tricarboxylic acid (TCA) cycle by increasing the acetylation of key enzymes in the TCA. Furthermore, BN2 enhanced the expression of indispensable genes for the colonic mucosal barrier, including antimicrobial peptides (porcine β defensin 1, pBD1; porcine β defensin 2, pBD2; and proline-arginine rich 39-amino acid peptide, PR39), tight junction proteins, and improved colonic microbiome composition. Based on these findings, we found that BN2 alleviated growth restriction and diarrhea, and modulated the expression of antimicrobial peptides, tight junction proteins, and cytokines to reduce colonic barrier function dysfunction in weaned piglets challenged with ETEC. Mechanistically, we confirmed that BN2 elevated the protein expression of acetylation of histone 3 lysin 27 (H3K27ac) and enhanced the binding of acH3K27 to the promoter regions of pBD1 and PR39. Conclusions Supplementation with BN2 improved growth performance, supported colonic health, and enhanced disease resistance in weaned piglets challenged with ETEC. This offers new insights for nutrients-based strategies against ETEC infection. Butyrate niacin colonic barrier function Escherichia coli weaned piglets Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementaryfile1.docx Supplementaryfile2.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 12 Feb, 2026 Reviews received at journal 11 Feb, 2026 Reviews received at journal 10 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers agreed at journal 30 Dec, 2025 Reviews received at journal 21 Nov, 2025 Reviewers agreed at journal 20 Nov, 2025 Reviewers agreed at journal 16 Nov, 2025 Reviewers invited by journal 14 Nov, 2025 Editor assigned by journal 12 Nov, 2025 Submission checks completed at journal 12 Nov, 2025 First submitted to journal 08 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8061761","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":549737417,"identity":"6e97c015-9e7d-4eb2-8f5e-eab7c26197cb","order_by":0,"name":"Qingsong Tang","email":"","orcid":"","institution":"Guangdong Academy of Agricultural Sciences","correspondingAuthor":false,"prefix":"","firstName":"Qingsong","middleName":"","lastName":"Tang","suffix":""},{"id":549737419,"identity":"0cd80a0c-a9cb-4a63-b926-65eb0d627f31","order_by":1,"name":"Rui Zhen","email":"","orcid":"","institution":"Guangdong Academy of Agricultural 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piglets","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-animal-science-and-biotechnology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jasb","sideBox":"Learn more about [Journal of Animal Science and Biotechnology](http://jasbsci.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jasb/default.aspx","title":"Journal of Animal Science and Biotechnology","twitterHandle":"@animalplantsci","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Butyrate, niacin, colonic barrier function, Escherichia coli, weaned piglets","lastPublishedDoi":"10.21203/rs.3.rs-8061761/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8061761/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eButyrate is the primary energy substrate in the colon, whereas niacin can enhance energy metabolic flux by increasing nicotinamide adenine dinucleotide (NAD) synthesis. Therefore, this study aimed to investigate the effects of combining butyrate with niacin on colonic metabolism and resistance to enterotoxigenic \u003cem\u003eEscherichia coli\u003c/em\u003e (ETEC) infection in weaned piglets. In this study, two animal experiments were designed to observe the optimal butyrate-to-niacin ratio and assess their responses to the ETEC challenge.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eSupplementation with Butyrate and niacin at a ratio of 100:2 (2000 mg/kg butyrate and 40 mg/kg niacin, BN2) increased the average daily gain (ADG) and reduced the diarrhea incidence. We also observed an increase in the levels of NAD in the colon of weaned piglets. Notably, BN2 promoted amino acid anabolism in the colon and enhanced glycolysis and the tricarboxylic acid (TCA) cycle by increasing the acetylation of key enzymes in the TCA. Furthermore, BN2 enhanced the expression of indispensable genes for the colonic mucosal barrier, including antimicrobial peptides (porcine β defensin 1, pBD1; porcine β defensin 2, pBD2; and proline-arginine rich 39-amino acid peptide, PR39), tight junction proteins, and improved colonic microbiome composition. Based on these findings, we found that BN2 alleviated growth restriction and diarrhea, and modulated the expression of antimicrobial peptides, tight junction proteins, and cytokines to reduce colonic barrier function dysfunction in weaned piglets challenged with ETEC. Mechanistically, we confirmed that BN2 elevated the protein expression of acetylation of histone 3 lysin 27 (H3K27ac) and enhanced the binding of acH3K27 to the promoter regions of pBD1 and PR39.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eSupplementation with BN2 improved growth performance, supported colonic health, and enhanced disease resistance in weaned piglets challenged with ETEC. This offers new insights for nutrients-based strategies against ETEC infection.\u003c/p\u003e","manuscriptTitle":"Butyrate combined with niacin promotes colonic metabolism and antimicrobial peptide expression to alleviate ETEC-induced colonic barrier dysfunction in weaned piglets","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-25 19:31:22","doi":"10.21203/rs.3.rs-8061761/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-12T06:27:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-11T11:01:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-10T22:04:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285326405139250141738475485258968233270","date":"2026-02-05T06:22:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"167309136052663212776487585550173822857","date":"2026-02-04T15:14:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"176612167352032664606356825202046813423","date":"2025-12-30T05:25:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-21T13:48:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319090324346753823409243570659884081875","date":"2025-11-20T08:28:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98962077612402629965200648644527132047","date":"2025-11-16T14:22:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-14T08:29:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-13T01:55:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-13T01:54:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Animal Science and Biotechnology","date":"2025-11-08T06:17:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-animal-science-and-biotechnology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jasb","sideBox":"Learn more about [Journal of Animal Science and Biotechnology](http://jasbsci.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jasb/default.aspx","title":"Journal of Animal Science and Biotechnology","twitterHandle":"@animalplantsci","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6f4cbe58-d3d0-4a75-aebd-eea221685526","owner":[],"postedDate":"November 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-01T02:55:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-25 19:31:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8061761","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8061761","identity":"rs-8061761","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}