The Human Diets & Microbiome Initiative: A five-country analysis of geographic and dietary drivers of gut microbiome composition and genomic variation

The Human Diets & Microbiome Initiative: A five-country analysis of geographic and dietary drivers of gut microbiome composition and genomic variation | 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 The Human Diets & Microbiome Initiative: A five-country analysis of geographic and dietary drivers of gut microbiome composition and genomic variation Andrew Bartko, Lora Khatib, Renee Oles, Alejandra Hernández, Tyler Myers, and 40 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8436332/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 Human diet and lifestyle vary widely across cultures, shaping global diversity in gut microbiome composition and function. However, comparable cross-population studies have been limited by methodological heterogeneity. The Human Diets and Microbiome Initiative (THDMI) integrates standardized recruitment, dietary assessment, and shotgun metagenomics across 1,976 participants from the United States, United Kingdom, Spain, Mexico, and Japan to disentangle biological from technical variation. We observed pronounced geographic differences in nutrient intake, food consumption, and microbial composition, with both shared and country-specific taxa linked to diet quality. Sparse canonical correlation and machine-learning analyses revealed that microbiome–diet associations were largely population-specific, with limited cross-country generalization. Strain-level analyses further uncovered significant genomic differentiation of gut microbes, reflecting localized dietary and ecological pressures. Together, these results show that while core microbial responses to healthy eating exist, the structure and function of the human gut microbiome are profoundly shaped by culture, geography, and long-term dietary practices. Biological sciences/Microbiology/Microbial communities/Microbiome Health sciences/Gastroenterology/Gastrointestinal system Full Text Additional Declarations Yes there is potential Competing Interest. Rob Knight is a scientific advisory board member, and consultant for BiomeSense, Inc., has equity and receives income. He is a scientific advisory board member and has equity in GenCirq. He has equity in and acts as a consultant for Cybele. He is a Vice President and board member of Microbiota Vault, Inc. He is a board member of N=1 IBS advisory board and receives income. He is a Senior Visiting Fellow of HKUST Jockey Club Institute for Advanced Study. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. Nicole Litwin was employed by Center for Microbiome Innovation at the time of the project. Patrick Veiga, Jan Knol, Hana Koutnikova, Soline Chaumont, Aurélie Cotillard, Muriel Derrien, and Manolo Laiola were employees of Danone Research & Innovation at the time of the project. Daniel McDonald is a consultant for and has equity in BiomeSense, Inc. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. Andrew Bartko is a founder of Guilden Corporation and is an equity owner. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. Supplementary Files supplementaltables.xlsx Supplementary Tables supplementaryfigures.pdf Supplementary Figures 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-8436332","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":580626038,"identity":"a4a55daa-d50e-4dcd-8783-17cbbd538156","order_by":0,"name":"Andrew 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He is a scientific advisory board member and has equity in GenCirq. He has equity in and acts as a consultant for Cybele. He is a Vice President and board member of Microbiota Vault, Inc. He is a board member of N=1 IBS advisory board and receives income. He is a Senior Visiting Fellow of HKUST Jockey Club Institute for Advanced Study. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. Nicole Litwin was employed by Center for Microbiome Innovation at the time of the project. Patrick Veiga, Jan Knol, Hana Koutnikova, Soline Chaumont, Aurélie Cotillard, Muriel Derrien, and Manolo Laiola were employees of Danone Research \u0026 Innovation at the time of the project. Daniel McDonald is a consultant for and has equity in BiomeSense, Inc. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. Andrew Bartko is a founder of Guilden Corporation and is an equity owner. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.","formattedTitle":"The Human Diets \u0026amp; Microbiome Initiative: A five-country analysis of geographic and dietary drivers of gut microbiome composition and genomic variation","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8436332/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8436332/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHuman diet and lifestyle vary widely across cultures, shaping global diversity in gut microbiome composition and function. 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