Supplementing RP-Arg during the gestation and lactation periods of grazing sheep reprograms liver metabolism in offspring lambs by increasing IGF-1 in milk

Supplementing RP-Arg during the gestation and lactation periods of grazing sheep reprograms liver metabolism in offspring lambs by increasing IGF-1 in milk | 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 Supplementing RP-Arg during the gestation and lactation periods of grazing sheep reprograms liver metabolism in offspring lambs by increasing IGF-1 in milk Xiangjian Peng, Yuyang Xue, Hailiang Wang, Shanshan Nan, Yayin Qi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7805924/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Feb, 2026 Read the published version in Animal Microbiome → Version 1 posted 13 You are reading this latest preprint version Abstract The nutritional status of ewes during gestation and lactation is a key determinant of lamb growth performance. Supplementing rumen-protected arginine (RP-Arg) during these stages induces maternal metabolic adaptation, thereby maintaining fetal developmental homeostasis. However, the sustained effects of such metabolic regulation on postnatal lamb growth and immune function remain unclear. This study employed a combined comparative approach of 16S rRNA sequencing and metabolomics analysis to reveal differential effects of concentrate supplementation and RP-Arg on offspring gut microbiota restructuring and hepatic metabolic reprogramming. Compared to the CON group, both the SF (CON + concentrate) and ARG (SF + RP-Arg) groups significantly improved early growth performance in lambs (P < 0.05), with the ARG group exhibiting a significantly higher growth rate than the SF group (P < 0.05). Milk protein content was significantly increased in the SF and ARG groups relative to the CON group (P < 0.05). Notably, compared to the SF group, ARG supplementation elevated colostrum lactoferrin (LF) and insulin-like growth factor-1 (IGF-1) concentrations by 28.4% and 34.1%, respectively (P < 0.05). 16S rRNA sequencing revealed significant enrichment of the Bacteroidetes phylum following RP-Arg supplementation. Liver metabolomics analysis revealed that RP-Arg synergistically promotes offspring growth advantage and immune maturation by enhancing amino acid digestion efficiency, transmembrane transport capacity, and metabolic flux redistribution. This study elucidates a novel maternal-fetal interaction mechanism: strategically incorporating RP-Arg into sheep diets during the reproductive cycle modulates ewe colostrum composition and lamb gut-liver axis function, ultimately synergistically optimizing growth trajectories and immune development within grazing systems. rumen-bypass arginine maternal-fetal axis immunometabolism Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementarydocuments.docx Cite Share Download PDF Status: Published Journal Publication published 11 Feb, 2026 Read the published version in Animal Microbiome → Version 1 posted Editorial decision: Revision requested 06 Dec, 2025 Reviews received at journal 03 Dec, 2025 Reviews received at journal 30 Nov, 2025 Reviews received at journal 12 Nov, 2025 Reviewers agreed at journal 06 Nov, 2025 Reviews received at journal 06 Nov, 2025 Reviewers agreed at journal 04 Nov, 2025 Reviewers agreed at journal 04 Nov, 2025 Reviewers agreed at journal 04 Nov, 2025 Reviewers invited by journal 03 Nov, 2025 Editor assigned by journal 02 Nov, 2025 Submission checks completed at journal 30 Oct, 2025 First submitted to journal 30 Oct, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7805924","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":544090885,"identity":"8d98f1e1-dd4d-405d-b00f-187c56ed2737","order_by":0,"name":"Xiangjian Peng","email":"","orcid":"","institution":"Shihezi University","correspondingAuthor":false,"prefix":"","firstName":"Xiangjian","middleName":"","lastName":"Peng","suffix":""},{"id":544090886,"identity":"4cfe164a-cfe8-4680-be51-963360854d1d","order_by":1,"name":"Yuyang Xue","email":"","orcid":"","institution":"Shihezi 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milk","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":"animal-microbiome","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"amic","sideBox":"Learn more about [Animal Microbiome](http://animalmicrobiome.biomedcentral.com)","snPcode":"42523","submissionUrl":"https://submission.nature.com/new-submission/42523/3","title":"Animal Microbiome","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"rumen-bypass arginine, maternal-fetal axis, immunometabolism","lastPublishedDoi":"10.21203/rs.3.rs-7805924/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7805924/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe nutritional status of ewes during gestation and lactation is a key determinant of lamb growth performance. Supplementing rumen-protected arginine (RP-Arg) during these stages induces maternal metabolic adaptation, thereby maintaining fetal developmental homeostasis. However, the sustained effects of such metabolic regulation on postnatal lamb growth and immune function remain unclear. This study employed a combined comparative approach of 16S rRNA sequencing and metabolomics analysis to reveal differential effects of concentrate supplementation and RP-Arg on offspring gut microbiota restructuring and hepatic metabolic reprogramming. Compared to the CON group, both the SF (CON\u0026thinsp;+\u0026thinsp;concentrate) and ARG (SF\u0026thinsp;+\u0026thinsp;RP-Arg) groups significantly improved early growth performance in lambs (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with the ARG group exhibiting a significantly higher growth rate than the SF group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Milk protein content was significantly increased in the SF and ARG groups relative to the CON group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Notably, compared to the SF group, ARG supplementation elevated colostrum lactoferrin (LF) and insulin-like growth factor-1 (IGF-1) concentrations by 28.4% and 34.1%, respectively (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). 16S rRNA sequencing revealed significant enrichment of the Bacteroidetes phylum following RP-Arg supplementation. Liver metabolomics analysis revealed that RP-Arg synergistically promotes offspring growth advantage and immune maturation by enhancing amino acid digestion efficiency, transmembrane transport capacity, and metabolic flux redistribution. This study elucidates a novel maternal-fetal interaction mechanism: strategically incorporating RP-Arg into sheep diets during the reproductive cycle modulates ewe colostrum composition and lamb gut-liver axis function, ultimately synergistically optimizing growth trajectories and immune development within grazing systems.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","manuscriptTitle":"Supplementing RP-Arg during the gestation and lactation periods of grazing sheep reprograms liver metabolism in offspring lambs by increasing IGF-1 in milk","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-13 19:18:44","doi":"10.21203/rs.3.rs-7805924/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-06T23:28:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-03T06:12:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-01T04:32:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-12T17:14:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256749999374529439789310334531381546817","date":"2025-11-07T03:14:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-06T16:08:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"184922165875152432776071371043037384296","date":"2025-11-04T17:16:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"109354227702140355692546114941306462664","date":"2025-11-04T15:52:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"191385270672914560209450866793318080467","date":"2025-11-04T12:18:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-04T04:02:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-02T23:37:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-30T12:08:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Animal Microbiome","date":"2025-10-30T11:57:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"animal-microbiome","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"amic","sideBox":"Learn more about [Animal Microbiome](http://animalmicrobiome.biomedcentral.com)","snPcode":"42523","submissionUrl":"https://submission.nature.com/new-submission/42523/3","title":"Animal Microbiome","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ecfd8e0-d850-4adb-947b-e2b7e8c50b7a","owner":[],"postedDate":"November 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T15:59:41+00:00","versionOfRecord":{"articleIdentity":"rs-7805924","link":"https://doi.org/10.1186/s42523-026-00526-z","journal":{"identity":"animal-microbiome","isVorOnly":false,"title":"Animal Microbiome"},"publishedOn":"2026-02-11 15:56:58","publishedOnDateReadable":"February 11th, 2026"},"versionCreatedAt":"2025-11-13 19:18:44","video":"","vorDoi":"10.1186/s42523-026-00526-z","vorDoiUrl":"https://doi.org/10.1186/s42523-026-00526-z","workflowStages":[]},"version":"v1","identity":"rs-7805924","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7805924","identity":"rs-7805924","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}