Abstract
Both gut microbiota dysbiosis and disrupted cholesterol metabolism are associated with colorectal cancer (CRC). While the interactions between these two factors have been well explored in diseases such as cardiovascular disease and atherosclerosis, their interactions and underlying mechanisms in CRC pathogenesis remain insufficiently explored, constituting a critical area for further investigation. This review examines the complex relationship between gut microbiota and cholesterol metabolism in CRC development from 2 perspectives: how specific gut microbial species can increase CRC risk by modulating cholesterol metabolism, particularly through bile acids and oxysterols, and how disrupted cholesterol metabolism can exacerbate microbial dysbiosis and promote CRC. The bidirectional relationship between gut dysbiosis and cholesterol dysregulation creates a vicious cycle that drives CRC development. Moreover, the potential of targeting the gut microbiome and cholesterol metabolism to develop new strategies for preventing and treating CRC is discussed, highlighting the promise of certain bacterial strains that exert protective effects via cholesterol-lowering mechanisms. By elucidating the intricate connections between gut microbiota, cholesterol metabolism, and CRC, this review paves the way for innovative approaches in CRC prevention and therapy.