Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment

Background: Elevated serum Cholesterol levels are linked to an increased risk of colorectal adenomas and colorectal Cancer (CRC), yet the role of serum low-density lipoprotein (LDL) in CRC development remains unclear. This study explores the impact of Cholesterol on tumor growth and the potential therapeutic effects of Lactobacillus and Simvastatin.

Methods: We utilized a cecal tumor xenograft mouse model with LDLR^-/- mice to assess the effects of high Cholesterol levels on tumor growth. Additionally, the role of gut microbiota remodeling and cholesterol-lowering strategies was investigated using Lactobacillus supplementation and Simvastatin treatment.

Results: LDLR^-/- mice on a high-cholesterol diet developed significantly larger tumors (P < 0.05) and exhibited exacerbated malignancy, as indicated by HE and Ki-67 staining. Lactobacillus supplementation reduced tumor growth (P < 0.05), lowered serum Cholesterol levels, and altered the gut microbiota composition, increasing the relative abundance of beneficial Bacterial taxa. Simvastatin treatment reduced PD-L1 expression in CRC cells by lowering Cholesterol levels, which was associated with decreased CRC proliferation, reduced serum LDL levels, and enhanced T cell infiltration in the tumor microenvironment.

Conclusion: Elevated serum Cholesterol promotes CRC progression, while gut microbiota remodeling through Lactobacillus supplementation and cholesterol-lowering interventions, such as Simvastatin, show potential in mitigating tumor growth and enhancing antitumor immune responses. These findings highlight the importance of Cholesterol management in CRC treatment strategies.

Lactobacillus; Colorectal cancer; Gut microbiota; Low-density lipoprotein; Simvastatin.