Revealing Protein-Level Functional Redundancy in the Human Gut Microbiome using Ultra-deep Metaproteomics

Revealing Protein-Level Functional Redundancy in the Human Gut Microbiome using Ultra-deep Metaproteomics | 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 Revealing Protein-Level Functional Redundancy in the Human Gut Microbiome using Ultra-deep Metaproteomics Leyuan Li, Zhibin Ning, Xu Zhang, James Butcher, Caitlin Simopoulos, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-785043/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 Functional redundancy is a key property of ecosystems and represents the fact that phylogenetically unrelated taxa can play similar functional roles within an ecosystem. The redundancy of potential functions (or DNA-level functional redundancy) of human microbiomes has been recently quantified using metagenomics data. Yet, the redundancy of functions that are actually expressed in the human microbiome has never been quantitatively explored. Here, we quantify the protein-level functional redundancy in the human gut microbiome for the first time using metaproteomics and network approaches. In particular, our ultra-deep metaproteomics approach revealed high protein-level functional redundancy in the human gut microbiome and high nestedness in the corresponding proteomic content networks (i.e., the bipartite graphs connecting taxa to their expressed functions). However, due to selective functional expression, the protein-level functional redundancy is lower than the DNA-level functional redundancy in the human gut microbiome. Using a consumer-resource population dynamics model, we found that such a selective functional expression contributes to the high richness and diversity in the assembled microbial communities. We further examined multiple metaproteomics datasets and showed that various environmental factors, including individuality, biogeography, xenobiotics, and disease, significantly affect the protein-level functional redundancy. In particular, inflammation and several xenobiotics significantly diminish the protein-level functional redundancy. Finally, by projecting the bipartite proteomic content networks into the unipartite functional similarity networks of genera, we discovered functional hub genera across individual microbiomes, suggesting that there may be a universal principle of functional organization in microbiome assembly. General Microbiology Systems Biology Topology Computational Biology Bioinformatics General Biochemistry human microbiome functional redundancy metaproteomics Full Text Additional Declarations Yes there is potential Competing Interest. D.F., A.S. and D.R.M. have co-founded Biotagenics and MedBiome, clinical microbiomics companies. All other authors declare no potential conflicts of interest. Supplementary Files FRpaperSupplementarytables20210709LL.xlsx Supplementary Tables FRpaperSupplementarynotes20210712LL.docx Supplementary Notes FRpaperSupplementaryinformation20210712LL.docx Supplementary Information 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. 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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-785043","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":44245643,"identity":"8745988a-032a-478c-a1c5-e50e930a2078","order_by":0,"name":"Leyuan Li","email":"","orcid":"","institution":"University of Ottawa","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Leyuan","middleName":"","lastName":"Li","suffix":""},{"id":44245644,"identity":"c45d9d54-1be3-48d1-a057-eb2fedad6725","order_by":1,"name":"Zhibin Ning","email":"","orcid":"","institution":"University of 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