Energy generation drives gut colonization by Bilophila wadsworthia

Energy generation drives gut colonization by Bilophila wadsworthia | 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 Energy generation drives gut colonization by Bilophila wadsworthia Lizbeth Sayavedra, Muhammad Yasir, Andrew Goldson, Arlaine Brion, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4502164/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 May, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract High-fat diets alter the gut microbiota composition and stimulate proliferation of the sulfidogenic bacterium Bilophila wadsworthia (Bw). Proliferation of B. wadsworthia is linked to gut inflammation, dysfunction of the intestinal barrier and bile acid metabolism but the genetic basis for its colonization of the gut remains largely unknown. In this study, we identified genes that facilitate gut colonization by B. wadsworthia under a high-fat diet, either with or without a simplified humanized microbial consortium (SIHUMI), by using a combination of ‘omics’ approaches, including genome-wide transposon mutagenesis, metatranscriptomics and untargeted metabolomics. Comparisons between mutants present in culture and mutants in the gut revealed 32 genes essential for gut colonization. These included two gene clusters related to bacterial microcompartment (BMC) formation and function, and a NADH dehydrogenase (hdrABC-flxABCD) important for energy metabolism in anaerobes. BMCs allow B. wadsworthia to metabolise the organosulfonate compounds taurine and isethionate (abundant in the mammalian gut) releasing H2S, acetate and possibly ethanol. Although the H2S concentration and B. wadsworthia abundance were at their highest in the absence of the SIHUMI, detrimental impacts on the host were exacerbated in the presence of the SIHUMI, based on gut permeability, the abundance of pro-inflammatory cytokines (IL-1a, IFN-G) and increased infiltration of macrophages in the liver. More genes were required by B. wadsworthia for gut colonization when they were grown with the SIHUMI consortia compared with growth in monoculture; the same was true for their ability to synthesise nucleotides and histidine. This suggests that microbial community composition plays a key role in modulation of the activity of this pathobiont. Biological sciences/Microbiology/Microbial genetics/Bacterial genes Health sciences/Pathogenesis Biological sciences/Molecular biology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TablesforSubmission.xlsx Supplementary Tables SupplementaryFigures.docx nrreportingsummary.pdf Reporting summary Cite Share Download PDF Status: Published Journal Publication published 30 May, 2025 Read the published version in Nature Communications → 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. 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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-4502164","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":324370439,"identity":"fb25dfe7-ccd6-4e4a-bc51-8e9030ae6fde","order_by":0,"name":"Lizbeth 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