Hypocholesterolemic effects of orally administrated Eubacterium coprostanoligenes in cynomolgus monkeys

Abstract

Orally administrated E. coprostanoligenes has been shown to decrease blood cholesterol concentrations in cholesterol-fed rabbits. In this study, the safety and efficacy of dietary E. coprostanoligenes to decrease blood cholesterol concentration were evaluated in cynomolgus monkeys. Nine adult male cynomolgus monkeys (Macaca fascicularis) were divided randomly into two groups: group A (five monkeys) and group B (four monkeys). Both groups were fed a hypercholesterolemic diet for 10 weeks. Then, group A received the hypercholesterolemic diet supplemented with E. coprostanoligenes (4 x 1010 cells) daily for 10 weeks and then the hypercholesterolemic diet with the same amount of heat-treated (1200C for 15 minutes) E. coprostanoligenes for another 10 weeks. Group B received the hypercholesterolemic diet with 4 x 1010 heat-treated E. coprostanoligenes daily for 10 weeks and then the same amount of live E. coprostanoligenes for another 10 weeks. No treatment-associated illness or death was observed throughout the experiment. Body weight and body temperature of individual monkeys were normal throughout the experiment. Oral administration of E. coprostanoligenes causes a significant (P < 0.05) decrease in plasma cholesterol in high-response monkeys. Low response monkeys fed dead E. coprostanoligenes experienced no change (P > 0.05) in blood cholesterol. Feeding E. coprostanoligenes markedly increased the ratio of coprostanol to cholesterol in contents and of mucosal cells of the stomach and all sections of the small and large intestine. Weight ratios of coprostanol to cholesterol in feces also were increased because of feeding the E. coprostanoligenes. Thus, viable E. coprostanoligenes reached the small intestine where they reduced cholesterol to coprostanol, thereby potentially decreasing cholesterol absorption. We hypothesize that this probable decrease in cholesterol absorption caused the observed decrease in blood cholesterol. In general, no adverse effects were shown on animals' general health status, hematology, blood biochemistry, gut mucosal histology parameters, or the incidence of bacterial translocation. These results suggest the use of a dietary supplement of E. coprostanoligenes to decrease the cholesterol in human.