Cheonggukjang, a gut microbiota-modulating Korean fermented food, improves cholesterol and bile acid metabolism

Hypercholesterolemia (HCE) is one of the major causal factors of the development of cardiovascular disease. <i>Cheonggukjang</i> (CGJ), a representative Korean fermented soybean paste, has multiple health benefits, including cholesterol-lowering effects; however, the effects of CGJ on detailed mechanisms in cholesterol and bile acid metabolism, and the correlation between gut microbiota alterations and cholesterol and bile acid metabolism remain unclear. In this study, mice were randomly divided into the normal diet (ND, 10% fat of total kcal), high-cholesterol and fat diet (HCFD, 1% cholesterol + 45% fat of total kcal), and HCFD with 30% of two different CGJ (CGJ#1 and CGJ#2). There were no significant differences in <i>α</i>-diversity indices between the two CGJs. However, CGJ#1 was dominated by <i>Bacillales</i>, while CGJ#2 was dominated by <i>Bactobacillales</i>. Compared to HCFD, CGJ significantly reduces body weight gain, lipid accumulation in the liver and adipose tissues, and serum lipid indicators by downregulating mRNA levels involved in lipogenesis. Furthermore, CGJ strongly changes mRNA levels associated with cholesterol and bile acid metabolism in the liver and ileum and increases bile acid excretion compared with HCFD. In addition, CGJ markedly recovers HCE-derived gut microbiota dysbiosis by altering the <i>α</i>-diversity index and decreasing the <i>Firmicutes/Bacteroidetes</i> ratio. Most significantly, this recovery of HCE-derived gut microbiota composition is significantly associated with the changes of HCE-associated markers. These observations strongly suggest that CGJ, regardless of its different microbial composition, improves HCE by changing cholesterol and bile acid metabolism via reorganization of gut microbiota imbalance.