Gut Microbiota-Dependent Choline Metabolism Drives Mammary Gland Lipid Redistribution via Microbial Metabolites

Gut Microbiota-Dependent Choline Metabolism Drives Mammary Gland Lipid Redistribution via Microbial Metabolites | 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 Gut Microbiota-Dependent Choline Metabolism Drives Mammary Gland Lipid Redistribution via Microbial Metabolites Lily Liu, Mengxue Hu, Min Yan, Songlin Liu, Weiqi Wang, Xu Luo, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6781247/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The mechanisms governing lipid allocation to the mammary gland (MG) during lactation remain poorly understood, particularly across mammalian species. Here, we identify choline-an essential nutrient with established roles in liver and brain function but uncharacterized effects on lactation-as a key regulator of mammary lipid metabolism through gut microbiota and their metabolites. Using complementary yak observational studies and mouse intervention models, we show that choline supplementation and yak-derived fecal microbiota transplantation (FMT) similarly enrich the abundance of Akkermansia muciniphila (A. muciniphila), increasing lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) levels. These metabolites enhance lipid accumulation in the MG of pregnant mice through CD36-mediated lipid uptake while modulating intestinal anti-inflammatory pathways, mirroring metabolic adaptations observed during human lactation. Our multi-omics analyses reveal a coordinated metabolic and immunological regulation through which gut microbiota translate dietary choline into MG lipid redistribution. These insights provide fundamental insights that bridge the gap between animal models and potential human applications, suggesting new avenues for investigating choline's role in mammalian lactation biology and nutritional interventions. Choline Mammary gland Lipid distribution Gut microbiota Microbial metabolites Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementalfigures.pdf OriginalimagesforWB.jpg Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-6781247","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":465039045,"identity":"9af80329-7663-44c1-8da3-678e29f92fda","order_by":0,"name":"Lily 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