Comparative Metagenomics of Vaginal Microbiomes Reveal Strain-Level Differences with Relevance to Colonization and Host-Microbe Interactions

Comparative Metagenomics of Vaginal Microbiomes Reveal Strain-Level Differences with Relevance to Colonization and Host-Microbe Interactions | 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 Comparative Metagenomics of Vaginal Microbiomes Reveal Strain-Level Differences with Relevance to Colonization and Host-Microbe Interactions Sai Ravi Chandra Nori, Calum Walsh, Fionnuala McAuliffe, Rebecca Moore, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4384089/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Mar, 2025 Read the published version in npj Biofilms and Microbiomes → Version 1 posted 10 You are reading this latest preprint version Abstract The vaginal microbiome, a relatively simple, low diversity ecosystem crucial for female health, is often dominated by Lactobacillus spp.. Studies of this community have often relied on short read amplicon sequencing, limiting the taxonomic resolution to genus or species level. More detailed strain-level data, facilitated by shotgun sequencing, can provide a greater understanding of the mechanisms of colonization and host-microbe interactions. In this study, we analysed 354 vaginal metagenomes from pregnant women in Ireland to investigate the metagenomic community state types and strain-level variations, particularly those involved in cell surface interface with the host. Our analysis showed the presence of multiple metagenomic subspecies across major vaginal bacteria with Lactobacillus crispatus and Lactobacillus iners being the most dominant. Detailed examination revealed distinct genes, including mucin-binding genes, present in Lactobacillus crispatus subspecies but absent in Lactobacillus iners. Within the dataset, we recovered 337 high-quality metagenome-assembled genomes and determined that L. crispatus harbours a greater number of strain-specific genes related to cell wall biogenesis, carbohydrate and amino acid metabolism compared to L. iners, with genes predicted to be involved in mucin binding and cell surface structure under positive selection in L. crispatus. Supplementing our dataset with publicly available genomes, we revealed a cell surface glycan gene cluster predominantly present in L. crispatus that is absent from L. iners and Gardnerella vaginalis. Overall, our comprehensive analysis offers new insights into the intra-species diversity of the vaginal microbiome, emphasising the importance of strain-specific variations in factors associated with colonisation and host-microbe interactions, which are essential for maintaining vaginal health. Biological sciences/Microbiology/Microbial communities/Microbiome Biological sciences/Microbiology/Bacteria/Metagenomics Full Text Additional Declarations (Not answered) Supplementary Files Supplementaryfigures.pdf Supplementarytables.xlsx Cite Share Download PDF Status: Published Journal Publication published 23 Mar, 2025 Read the published version in npj Biofilms and Microbiomes → Version 1 posted Editorial decision: revise 31 Jul, 2024 Review # 2 received at journal 27 May, 2024 Reviewer # 3 agreed at journal 24 May, 2024 Review # 1 received at journal 23 May, 2024 Reviewer # 2 agreed at journal 13 May, 2024 Reviewer # 1 agreed at journal 13 May, 2024 Reviewers invited by journal 12 May, 2024 Editor assigned by journal 12 May, 2024 Submission checks completed at journal 08 May, 2024 First submitted to journal 07 May, 2024 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. 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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-4384089","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":301492064,"identity":"42715456-c989-46cc-a4bb-ccdd622a9c73","order_by":0,"name":"Sai Ravi Chandra Nori","email":"","orcid":"https://orcid.org/0000-0003-2553-3156","institution":"Teagasc - The Irish Agriculture and Food Development Authority","correspondingAuthor":false,"prefix":"","firstName":"Sai","middleName":"Ravi Chandra","lastName":"Nori","suffix":""},{"id":301492065,"identity":"a000aa1b-3966-454e-8fcf-57a59ad9d933","order_by":1,"name":"Calum Walsh","email":"","orcid":"","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Calum","middleName":"","lastName":"Walsh","suffix":""},{"id":301492066,"identity":"ee57d4dd-b1bc-4b11-b58c-6318950454b6","order_by":2,"name":"Fionnuala McAuliffe","email":"","orcid":"","institution":"UCD Perinatal Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Fionnuala","middleName":"","lastName":"McAuliffe","suffix":""},{"id":301492069,"identity":"37b92e1e-1b1d-4a7d-83c8-f8c2eb58eb8c","order_by":3,"name":"Rebecca Moore","email":"","orcid":"","institution":"UCD Perinatal Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Rebecca","middleName":"","lastName":"Moore","suffix":""},{"id":301492067,"identity":"f4450d0b-8944-4f1d-a5f0-e0e9cc5460c1","order_by":4,"name":"Douwe van Sinderen","email":"","orcid":"https://orcid.org/0000-0003-1823-7957","institution":"University College Cork","correspondingAuthor":false,"prefix":"","firstName":"Douwe","middleName":"van","lastName":"Sinderen","suffix":""},{"id":301492068,"identity":"0dd19353-f3d0-4038-b73f-89bcf1c7c7dd","order_by":5,"name":"Conor Feehily","email":"","orcid":"","institution":"University of Glasgow","correspondingAuthor":false,"prefix":"","firstName":"Conor","middleName":"","lastName":"Feehily","suffix":""},{"id":301492063,"identity":"30044233-ad0c-43d0-9423-a224fbfab2ad","order_by":6,"name":"Paul Cotter","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYHACxgMwxgO4WAIBPSAtEjwMDMwGMM1Ea2GTOEBAJRiYs58Bml1jU2fP3vus+kOFnV1//+EHDA8qcGux7MkBajmWJsHDc9zsxoEzyckzbqQZMCScwa3F4ABQC2PDYQkeiTS2GwfbmJMZbgDdmNiGR8v5N1At8s/YCg7+q0+WPw+0IfEfHi034LawsTEcbDhsB7QXqKUBj19mPCs4kHAsTbLnTBqzxJljxxMMgX4BiuDWYs6fvPHBhxobfvb2Y4wfKmqq7eXOH3748EcNHoeBiAQkAbCTDuDWANWCDOzxqR4Fo2AUjIKRCQCmM1SvVKJQdwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-5465-9068","institution":"Teagasc - 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