Abstract

Obesity and dyslipidemia are hallmarks of metabolic and cardiovascular diseases. 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) ±75 mg 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 < 0.001), fasting plasma triglyceride (p < 0.001) and total cholesterol (p < 0.05). Microbiome analysis revealed that the relative abundance of Allobaculum, Bifidobacterium and Coriobacteriaceae taxa associated with lean phenotype, increased in WD + PDX mice. Gene expression analysis with linear mixed-effects model showed consistent downregulation of Dgat1, Cd36, Fiaf and upregulation of Fxr in duodenum, jejunum, ileum and colon in WD + PDX mice. Spearman correlations indicated that genera enriched in WD + PDX mice inversely correlated with fasting lipids and downregulated genes Dgat1, Cd36 and Fiaf while positively with upregulated gene Fxr. These results suggest that PDX in mice fed WD promoted systemic changes via regulation of the gut microbiota and gene expression in intestinal tract.

Highlights

  • Western diets high in saturated fat and processed meat are strongly implicated in the increasing prevalence of obesity, diabetes and cardiovascular diseases (CVD)[1]

  • Gene expression analysis with a linear mixed-effects model showed a consistent downregulation of Dgat[1], Cd36 and Fiaf and upregulation of Fxr in several intestinal segments either in duodenum, jejunum, ileum or colon in Western diet (WD) + PDX mice

  • In liver the significant inverse Spearman correlation between several genes related to lipid metabolism Prkaa, Hmgcr, Acat, Ldlr, Lpl, Slc27a2, Acot[3], Ppara, and Ppargc[1] and plasma triglyceride and between Lpl and plasma total cholesterol, indicates that polydextrose ingestion has metabolic effects in liver regulating circulating lipoproteins

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Summary

Introduction

Western diets high in saturated fat and processed meat are strongly implicated in the increasing prevalence of obesity, diabetes and cardiovascular diseases (CVD)[1]. Dyslipidemia is characterized by increased levels of plasma triglyceride-rich lipoproteins and non-HDL-cholesterol and reduced concentration of HDL cholesterol[2]. It affects almost 50% of individuals in Western populations, and is a hallmark for metabolic syndrome and CVD3, 4. Lifestyle management and healthy dieting habits, including reduced consumption of saturated fats as well as increased dietary fiber and unsaturated fats, are recommended as the first therapeutic choice for CVD and dyslipidemia[2, 5]. As a fermentable soluble fiber, PDX promotes the growth of bifidobacteria and lactobacilli while preventing the growth of detrimental bacteria, e.g. Clostridia, in addition to increasing SCFA production[16,17,18]. The exact mechanism of how PDX exerts these hypolipidemic effects has remained unclear

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