Multi-Omic Analyses of Dietary Fatty Acid-Microbe-Host Interactions Reveal Metaorganismal Lipid Metabolic Crosstalk Impacting Cardiometabolic Disease

Multi-Omic Analyses of Dietary Fatty Acid-Microbe-Host Interactions Reveal Metaorganismal Lipid Metabolic Crosstalk Impacting Cardiometabolic Disease | 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 Resource Multi-Omic Analyses of Dietary Fatty Acid-Microbe-Host Interactions Reveal Metaorganismal Lipid Metabolic Crosstalk Impacting Cardiometabolic Disease J. Mark Brown, Nour Mouannes, Amy Burrows, Anthony Horak, Venkateshwari Varadharajan, and 23 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9013531/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Following a meal, our gut microbiome and human cells collaborate via metaorganismal metabolic circuits to produce diverse nutrient metabolites that systemically circulate to influence health and disease. Although there are now several examples of bacterial fiber-, amino acid-, and micronutrient-derived metabolites impacting cardiometabolic disease, very little is known in regards to how diet-microbe-host interactions impact lipid homeostasis. Here we address this by defining dietary fatty acid substrate availability in germ-free versus conventionally-raised mice coupled to deep multi-omic metabolic phenotyping. Our data demonstrate that the effects of dietary saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) on the host lipidome, transcriptome, proteome and metabolome are uniquely impacted by resident microbiota. Also, the hepatic levels of both pro-inflammatory and pro-resolving lipid mediators are strongly influenced by dietary fatty acid-microbe interactions. This study presents a unique resource to the nutrition and metabolism research community to advance our understanding of metaorganismal lipid metabolism. Health sciences/Endocrinology/Endocrine system and metabolic diseases/Metabolic syndrome Biological sciences/Biochemistry/Lipids/Membrane lipids Nutrition Microbiome Metabolism Lipid Metabolomics Full Text Additional Declarations Yes there is potential Competing Interest. Kohey Kitao is CEO of Noster Inc., which provides microbiome-associated lipid metabolite reference standards and analytical protocols used in this study. Co-authors (Adarsh Sandhu, Chiaki Tomimoto, Kowa Tsuji and Yasunori Yonejima) are employees of Noster Inc. and contributed to the development of analytical reference standards and LC-MS/MS quantification protocols for microbiome-associated lipid metabolites used in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Supplementary Files FinalOnlineSupplement.pdf Online Supplement Cite Share Download PDF Status: Under Review 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. 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-9013531","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Resource","associatedPublications":[],"authors":[{"id":603887447,"identity":"a75f9f18-1338-4507-9e1a-0a0d16977210","order_by":0,"name":"J. 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