Tracing NAD⁺ metabolism uncovers adaptive coordination between host and microbiome during colitis

Tracing NAD⁺ metabolism uncovers adaptive coordination between host and microbiome during colitis | 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 Article Tracing NAD⁺ metabolism uncovers adaptive coordination between host and microbiome during colitis Melanie McReynolds, Abrar Alsaadi, Lina Welz, Anant Pothakamury, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8195970/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 Host-microbiota metabolic interactions critically regulate nicotinamide adenine dinucleotide (NAD+) homeostasis, and their disruption is increasingly linked to chronic diseases including inflammatory bowel disease (IBD). However, it remains unclear whether NAD+ dysregulation in IBD arises from impaired production, enhanced consumption, or both. Using multi-omics approaches and stable isotope-labeled NAD+ precursors administered via intravenous infusion in a murine model of dextran sulfate sodium (DSS)-induced colitis, we mapped tissue- and lumen-specific NAD+ metabolism under inflammatory stress. Our results reveal tissue-specific rewiring of NAD+ metabolism, with increased flux through the salvage pathway compensating for reduced de novo NAD+ synthesis from tryptophan. In parallel, microbial de novo NAD+ production was elevated, highlighting a cooperative host–microbiota response to inflammatory stress. These findings demonstrate differential regulation of NAD+ biosynthesis during acute colitis and underscore the dynamic interplay between host and microbial metabolism in maintaining NAD+ homeostasis under inflammatory conditions. Biological sciences/Biochemistry/Metabolomics Health sciences/Diseases/Gastrointestinal diseases/Inflammatory bowel disease/Crohn's disease NAD+ IBD gut microbiota tryptophan nicotinamide DSS colitis Full Text Additional Declarations There is NO Competing Interest. 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. 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-8195970","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":550737888,"identity":"71435565-995d-487c-aaaf-50ffccaf59ec","order_by":0,"name":"Melanie 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