Inulin-Bentonite Hybrid Microparticles Enhance Orlistat Efficacy While Mitigating Gut Microbiota Disruption in a High-Fat Diet Rat Model

Inulin-Bentonite Hybrid Microparticles Enhance Orlistat Efficacy While Mitigating Gut Microbiota Disruption in a High-Fat Diet Rat Model | 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 Research Article Inulin-Bentonite Hybrid Microparticles Enhance Orlistat Efficacy While Mitigating Gut Microbiota Disruption in a High-Fat Diet Rat Model Amin Ariaee, Anthony Wignall, Hannah R. Wardill, Alex Hunter, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9262495/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Orlistat is an established pharmacotherapy for metabolic syndrome (MetS); however, its clinical utility is constrained by gastrointestinal adverse effects and gut microbiota disruption. This study evaluates hybrid inulin (INU)-bentonite (BEN) microparticles (InuClay) as a microbiota-protective adjunct to orlistat therapy. In vitro lipolysis under biorelevant fasted-state conditions demonstrated that InuClay significantly reduced free fatty acid liberation relative to untreated controls and INU alone (p < 0.01). In a 21-day high-fat diet rat model of MetS, InuClay and orlistat monotherapies reduced cumulative weight gain by 4.5% and 5.7%, respectively. Co-administration achieved a 7.7% reduction that was significantly greater than either monotherapy alone. Combination therapy also produced the greatest reduction in fasting blood glucose (27%) exceeding both InuClay monotherapy (12%) and orlistat monotherapy (16%). At the microbiota level InuClay co-administration prevented orlistat-induced Proteobacteria expansion (2.5-fold reduction versus orlistat alone) while selectively enriching butyrate-producing taxa including Lachnospiraceae (1.42-fold) and Blautia (11.8-fold) without significantly altering alpha diversity. Circulating markers of cellular injury were substantially lower with combination therapy, with lactate dehydrogenase decreased by 63% and aspartate aminotransferase by 23% versus controls. These reductions were absent with orlistat monotherapy. Collectively these findings establish InuClay as a dual-action adjunct that enhances orlistat efficacy while attenuating dysbiotic shifts and systemic markers of tissue stress. This approach represents a promising strategy for improving translational outcomes in lipase inhibitor-based MetS management. orlistat drug delivery adjunct obesity gut microbiota modulation inulin-bentonite hybrid metabolic syndrome. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 04 May, 2026 Reviewers agreed at journal 16 Apr, 2026 Reviewers invited by journal 04 Apr, 2026 Editor assigned by journal 01 Apr, 2026 Submission checks completed at journal 01 Apr, 2026 First submitted to journal 30 Mar, 2026 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-9262495","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":618745800,"identity":"ec2019e8-5e0e-4a4f-a2e2-f5e7799ae4a4","order_by":0,"name":"Amin Ariaee","email":"","orcid":"","institution":"Adelaide University","correspondingAuthor":false,"prefix":"","firstName":"Amin","middleName":"","lastName":"Ariaee","suffix":""},{"id":618745801,"identity":"a6c3d648-8d8c-4ef9-a380-3abaa2bcb9cb","order_by":1,"name":"Anthony Wignall","email":"","orcid":"","institution":"Adelaide University","correspondingAuthor":false,"prefix":"","firstName":"Anthony","middleName":"","lastName":"Wignall","suffix":""},{"id":618745802,"identity":"594fe916-beeb-47ee-9de6-5698f8286a87","order_by":2,"name":"Hannah R. 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This study evaluates hybrid inulin (INU)-bentonite (BEN) microparticles (InuClay) as a microbiota-protective adjunct to orlistat therapy. \u003cem\u003eIn vitro\u003c/em\u003e lipolysis under biorelevant fasted-state conditions demonstrated that InuClay significantly reduced free fatty acid liberation relative to untreated controls and INU alone (p \u0026lt; 0.01). In a 21-day high-fat diet rat model of MetS, InuClay and orlistat monotherapies reduced cumulative weight gain by 4.5% and 5.7%, respectively. Co-administration achieved a 7.7% reduction that was significantly greater than either monotherapy alone. Combination therapy also produced the greatest reduction in fasting blood glucose (27%) exceeding both InuClay monotherapy (12%) and orlistat monotherapy (16%). At the microbiota level InuClay co-administration prevented orlistat-induced \u003cem\u003eProteobacteria\u003c/em\u003e expansion (2.5-fold reduction versus orlistat alone) while selectively enriching butyrate-producing taxa including \u003cem\u003eLachnospiraceae\u003c/em\u003e(1.42-fold) and \u003cem\u003eBlautia\u003c/em\u003e (11.8-fold) without significantly altering alpha diversity. Circulating markers of cellular injury were substantially lower with combination therapy, with lactate dehydrogenase decreased by 63% and aspartate aminotransferase by 23% versus controls. These reductions were absent with orlistat monotherapy. Collectively these findings establish InuClay as a dual-action adjunct that enhances orlistat efficacy while attenuating dysbiotic shifts and systemic markers of tissue stress. 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