Diet-Induced Metabolic Improvements in a Hamster Model of Hypercholesterolemia Are Strongly Linked to Alterations of the Gut Microbiota

Department of Food Science and Technology, University of Nebraska, Lincoln, 68583-0919, USA.
Applied and Environmental Microbiology (Impact Factor: 3.67). 06/2009; 75(12):4175-84. DOI: 10.1128/AEM.00380-09
Source: PubMed


The mammalian gastrointestinal microbiota exerts a strong influence on host lipid and cholesterol metabolism. In this study,
we have characterized the interplay among diet, gut microbial ecology, and cholesterol metabolism in a hamster model of hypercholesterolemia.
Previous work in this model had shown that grain sorghum lipid extract (GSL) included in the diet significantly improved the
high-density lipoprotein (HDL)/non-HDL cholesterol equilibrium (T. P. Carr, C. L. Weller, V. L. Schlegel, S. L. Cuppett, D.
M. Guderian, Jr., and K. R. Johnson, J. Nutr. 135:2236-2240, 2005). Molecular analysis of the hamsters' fecal bacterial populations by pyrosequencing of 16S rRNA tags, PCR-denaturing
gradient gel electrophoresis, and Bifidobacterium-specific quantitative real-time PCR revealed that the improvements in cholesterol homeostasis induced through feeding the
hamsters GSL were strongly associated with alterations of the gut microbiota. Bifidobacteria, which significantly increased
in abundance in hamsters fed GSL, showed a strong positive association with HDL plasma cholesterol levels (r = 0.75; P = 0.001). The proportion of members of the family Coriobacteriaceae decreased when the hamsters were fed GSL and showed a high positive association with non-HDL plasma cholesterol levels (r = 0.84; P = 0.0002). These correlations were more significant than those between daily GSL intake and animal metabolic markers, implying
that the dietary effects on host cholesterol metabolism are conferred, at least in part, through an effect on the gut microbiota.
This study provides evidence that modulation of the gut microbiota-host metabolic interrelationship by dietary intervention
has the potential to improve mammalian cholesterol homeostasis, which has relevance for cardiovascular health.

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    • "Early work on this topic showed a bloom of species belonging to Erysipelotrichaceae (classified as Mollicutes at the time of that study) in diet-induced obese animals (Turnbaugh et al., 2008). In addition, higher levels of Erysipelotrichaceae in obese individuals (Zhang et al., 2009), and a drop of approximately 2.5-fold in the abundance of Erysipelotrichaceae taxa in a hamster model of hypercholesterolemia treated with an extract to improve cholesterol homeostasis (Martínez et al., 2009) have been observed. Subsequent studies have confirmed the association between this bacterial family and lipidemic profiles within the host. "

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    • "The major purpose of our work was to try to evaluate potential changes in the gut microbiota that could be due to the hypolipidemic treatment. Numerous studies have proposed that gut microbiota participates in the regulation of cholesterol metabolism [11] [13] [27]. Changing gut microbiota composition, mainly in favor of Bifidobacterium spp., led to an inhibition of the cholesterol synthesis pathway [13]. "
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