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

Abstract

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 ( ). 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.

Sorghum: An Underutilized Cereal Whole Grain with the Potential to Assist in the Prevention of Chronic Disease

“…An alternative mechanism for the cholesterol lowering effect of sorghum lipid extract was reported by Martinez et al (81) from research done with hamsters. They reported that sorghum lipid extract acts as a "prebiotic" to improve the host cholesterol metabolism through effects on gut microbiota.…”

“…Bifidobacteria significantly increased in the hamsters fed grain sorghum lipid extract and was positively associated with HDL plasma cholesterol levels. (81) In humans, this shift in bifidobacteria is associated with improved overall health, including reduced gut infections and suppression of colon cancer initiation. (82)(83)(84) Finally, sorghum lipids may also possess antiproliferation properties.…”

In Vivo Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

“…In addition to enhancing the abundance of strain IVS-1, the synbiotic used here also redressed the high-fatdiet-induced reduction in the level of bifidobacteria detected in rats that is often reported in the literature (41)(42)(43). Therefore, although no metabolic benefits were seen in the rat model used in our study, the synbiotic may be beneficial in other scenarios, as bifidobacteria are considered health-promoting organisms (6,26,(66)(67)(68).…”

“…A total of 28 individual colonies (2 to 3 per subject) were propagated. To classify isolates, DNA was extracted by using the phenol-chloroform extraction method (26), and the 16S rRNA gene was amplified by using the 8F and 1391R universal primers. The amplification product was purified (QIAquick PCR purification kit; Qiagen Inc., MD) and sequenced by a commercial provider (Eurofins MWG Operon, Huntsville, AL).…”

“…qRT-PCR was performed by using a Mastercycler Realplex2 instrument (Eppendorf AG, Hamburg, Germany). Each PCR was performed with 25-l volumes using real-time master mix containing SYBR (5 Prime Inc., Gaithersburg, MD) and either genus-specific primers for Bifidobacterium, F primer TCGCGTC(C/T)G GTGTGAAAG and R primer CACATCCAGC(A/G)TCCAC (25,26), or the strain-specific primers for B. adolescentis IVS-1 (described above), each at a concentration of 0.8 M. Annealing temperatures of 58°C and 61°C were used for the genus-and strain-specific PCRs, respectively. Standard curves for absolute quantification of bacterial cell numbers were prepared by using cultures of B. adolescentis IVS-1 grown overnight (14 h), as described previously (25,26).…”