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Polydextrose (PDX), a soluble fiber has lipid lowering effects. We hypothesize that PDX reduces triglycerides and cholesterol by influencing gut microbiota, which in turn modulate intestinal gene expression. C57BL\/6 male mice were fed a Western diet (WD) \u00b175\u2009mg PDX twice daily by oral gavage for 14 days. Body weight and food intake were monitored daily. Fasting plasma lipids, caecal microbiota and gene expression in intestine and liver were measured after 14 days of feeding. PDX supplementation to WD significantly reduced food intake (p\u2009&lt;\u20090.001), fasting plasma triglyceride (p\u2009&lt;\u20090.001) and total cholesterol (p\u2009&lt;\u20090.05). Microbiome analysis revealed that the relative abundance of <jats:italic>Allobaculum<\/jats:italic>, <jats:italic>Bifidobacterium and Coriobacteriaceae<\/jats:italic> taxa associated with lean phenotype, increased in WD\u2009+\u2009PDX mice. Gene expression analysis with linear mixed-effects model showed consistent downregulation of <jats:italic>Dgat1<\/jats:italic>, <jats:italic>Cd36<\/jats:italic>, <jats:italic>Fiaf<\/jats:italic> and upregulation of <jats:italic>Fxr<\/jats:italic> in duodenum, jejunum, ileum and colon in WD\u2009+\u2009PDX mice. Spearman correlations indicated that genera enriched in WD\u2009+\u2009PDX mice inversely correlated with fasting lipids and downregulated genes <jats:italic>Dgat1<\/jats:italic>, <jats:italic>Cd36<\/jats:italic> and <jats:italic>Fiaf<\/jats:italic> while positively with upregulated gene <jats:italic>Fxr<\/jats:italic>. These results suggest that PDX in mice fed WD promoted systemic changes via regulation of the gut microbiota and gene expression in intestinal tract.<\/jats:p>","DOI":"10.1038\/s41598-017-05259-3","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T10:00:57Z","timestamp":1499421657000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Polydextrose changes the gut microbiome and attenuates fasting triglyceride and cholesterol levels in Western diet fed mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Ghulam Shere","family":"Raza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heli","family":"Putaala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-9575","authenticated-orcid":false,"given":"Ashley A.","family":"Hibberd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esa","family":"Alhoniemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsti","family":"Tiihonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari Antero","family":"M\u00e4kel\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Herzig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,13]]},"reference":[{"key":"5259_CR1","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1161\/CIRCULATIONAHA.108.771881","volume":"118","author":"C Heidemann","year":"2008","unstructured":"Heidemann, C. et al. 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