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

The mammalian gastrointestinal microbiota exerts a strong influence on host lipid and cholesterol metab-olism. 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 popu-lations by pyrosequencing of 16S rRNA tags, PCR-denaturing gradient gel electrophoresis, and Bifidobacte-rium-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. Bifidobac-teria, 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 Coriobac-teriaceae 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 metab-olism are conferred, at least in part, through an effect on the gut microbiota. This study provides evidence tha