{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:34:48Z","timestamp":1793658888620,"version":"4.5.1"},"posted":{"date-parts":[[2025,11,21]]},"group-title":"Nutrition","reference-count":118,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Dietary fiber supplementation can reduce cardiometabolic risk, but its effective use is limited by incomplete understanding of fibre-microbiome interactions and highly individualized responses. We tested acacia gum (AG; fermentable fibre), resistant starch type 4 (RS4; fermentable fibre), and microcrystalline cellulose (MCC; non-fermentable control fibre) in a six-week randomized trial in adults with excess body weight. Multi-omics profiling revealed distinct, structure-specific microbiota and short-chain fatty acid shifts with AG and RS4, which were not directly linked to physiological outcomes. Improvements in inflammation, gut barrier function, and satiety occurred across all arms, indicating fermentation-independent effects. AG reduced plasma ghrelin, linked to microbial carbohydrate-active enzyme genes targeting its structures. Machine-learning models predicted individualized, fiber-specific effects on blood pressure (AG) and C-reactive protein (RS4) from microbial pathways and fecal bile acids. These findings delineate fermentation-dependent and independent mechanisms of fibre action and provide a mechanistic basis for personalized fibre supplementation.<\/jats:p>\n                <jats:p>\n                  <jats:bold>Trial registration:<\/jats:bold>\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT02322112\">NCT02322112<\/jats:ext-link>\n                <\/jats:p>","DOI":"10.1101\/2025.11.20.25340625","type":"posted-content","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T22:50:14Z","timestamp":1763765414000},"source":"Crossref","is-referenced-by-count":2,"title":["Mechanistic insights into microbiome-dependent and personalized responses to dietary fibre in a randomized 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