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Totum\u2010448, a polyphenol\u2010rich blend of five plant extracts and choline, was developed to target MASLD progression. This study evaluated the dose\u2010dependent effects of Totum\u2010448 and their sustainability after supplementation cessation on MASLD features and cecal microbiota. Male hamsters were fed a normal diet, a Western diet (WD), or WD supplemented with Totum\u2010448 (3.5% or 5% w\/w) for 12\u2009weeks (dose\u2013response study). A parallel 18\u2010week on\/off study included 12\u2009weeks of Totum\u2010448 (5% w\/w) followed by a 6\u2010week cessation period. Totum\u2010448 dose\u2010dependently reduced hepatic and circulating triglycerides, total cholesterol, and free fatty acids, independently of any changes in body composition. Gene markers of liver inflammation (\n                    <jats:italic>Tgfb1<\/jats:italic>\n                    ,\n                    <jats:italic>Il1b, Ccl2<\/jats:italic>\n                    ,\n                    <jats:italic>Il6<\/jats:italic>\n                    ) and fibrosis (\n                    <jats:italic>Col3a1, Vcam<\/jats:italic>\n                    ) were downregulated with the highest dose of Totum\u2010448 only. Supplementation cessation led to a gradual rebound in serum and liver lipid levels and in relative expression of gene markers of hepatic inflammation and fibrosis, resulting in the loss of the majority of the benefits conferred by Totum\u2010448, although partial effects on hepatic steatosis and hepatocyte ballooning were maintained. Cecal microbiota analysis revealed modulation of the relative abundance of\n                    <jats:italic>Acetatifactor<\/jats:italic>\n                    ,\n                    <jats:italic>Alloprevotella<\/jats:italic>\n                    ,\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    , and\n                    <jats:italic>Lawsonibacter<\/jats:italic>\n                    , with identified correlations with certain metabolic outcomes. In conclusion, Totum\u2010448 demonstrated dose\u2010dependent improvements in key MASLD features in WD\u2010fed hamsters which gradually diminished after supplementation stopped. These findings underscore its therapeutic potential in MASLD management. The correlations with microbiota changes suggest a possible gut\u2013liver axis role in its effects.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.70904","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T10:40:25Z","timestamp":1756809625000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Totum\u2010448 Improves\n                    <scp>MASLD<\/scp>\n                    and Modulates Microbiota in Hamsters: Dose\u2013Response Study and Effects of Supplementation Cessation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0761-3355","authenticated-orcid":false,"given":"Vivien","family":"Chavanelle","sequence":"first","affiliation":[{"name":"Valbiotis R&amp;D Center Valbiotis  P\u00e9rigny 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