The effect of Lycium barbarum polysaccharides on the intestinal flora of mice with NAFLD-related colon cancer liver metastasis

Colorectal cancer liver metastasis (CRLM) is the main cause of high mortality in patients with colorectal cancer. Non-alcoholic fatty liver disease (NAFLD) promotes CRLM. Lycium barbarum polysaccharides (LBP) can inhibit the proliferation of colorectal cancer cells and treat NAFLD, but it is not clear whether LBP can inhibit NAFLD-related CRLM. Therefore, in this study, a CRLM model was constructed by intrasplenic injection of MC38 cells in a NAFLD mouse model to detect the effects of LBP on CRLM and on liver lipid metabolism indicators, liver function indicators, and colonic barrier function. A pseudo-germ-free mouse model combined with fecal microbiota transplantation technology was used to verify the role of the intestinal microbiota in LBP inhibition of CRLM. 16S rRNA sequencing technology was applied to analyze the changes in the intestinal microbiota after LBP intervention, and Spearman correlation analysis was used to explore the correlation between bacterial genera and liver lipid metabolism indicators and liver function indicators. The aim was to investigate the effect of LBP on NAFLD-related colorectal cancer liver metastasis and its possible mechanism. The results showed that LBP could inhibit colorectal cancer liver metastasis, and the intestinal microbiota played a key mediating role. After LBP intervention, the abundance and diversity of the intestinal microbiota in mice were significantly increased. At the phylum level, the abundance of Bacteroidota bacteria in the NAFLD group was significantly lower than that in the control group, while the abundance of Deferribacterota bacteria was significantly higher. After LBP intervention, the abundance of Bacteroidota bacteria increased significantly, while the abundance of Deferribacterota bacteria decreased significantly. The Bacteroidota/Firmicutes ratio in the NAFLD group was significantly lower than that in the control group, and after LBP intervention, the ratio increased, but there was no statistical difference compared with the NAFLD group. At the genus level, the abundances of Phocaeicola A, Parabacteroides_B, Fimenecus, Tidjanibacter, Alloprevotella, UBA7173, CAG-873, Cryptobacteroides, Odoribacter, Evtepia, Alistipes A, UBA3263, Bacteroides H, Butyricimonas, Dehalobacterium, C-19, Emergencia, Duncaniella, and Berryella were significantly higher after LBP intervention compared with the NAFLD group. Cryptobacteroides, Evtepia, and Bacteroides H were positively correlated with TC, TG, LDL, AST, and ALT, and negatively correlated with HDL. This study provides direct evidence that LBP can be used as a new drug to inhibit colorectal cancer liver metastasis.