Capsaicin shapes gut microbiota and pre-metastatic niche to facilitate cancer metastasis to liver

Abstract Background Dietary factors are fundamental in tumorigenesis throughout our lifetime. A spicy diet has been ambiguous about the development of cancers, especially in the study of colon cancer metastasis. It is unclear whether long-term, high dose intake of capsaicin could promote cancer metastasis. Here, we utilized a metastasis mouse model to test the potential pro-metastasis role of capsaicin. Results Long-term continuous administration of capsaicin diet to mice will promote the formation of liver pre-metastatic niche to facilitate colon cancer cells metastasis. Bacteria translocation to liver is clearly observed. Capsaicin increases intestinal barrier permeability and disrupts gut vascular barrier by altering the composition and abundance of gut microbiota. Capsaicin not only changes the abundance of mucin-related bacteria like Akkermanisa and Muribaculaceae , but also bacteria involved in bile acids metabolism. Dysregulated bile acids profile is related to NKT cells recruitment in pre-metastatic niche, primary bile acid α-MCA could enhance the recruitment of NKT cells, while secondary bile acids GUDCA and THDCA impairs the recruitment of NKT cells. Conclusion These findings reveal long term consumption of capsaicin would increase the risk of cancer metastasis through modulating the gut microbiota. Capsaicin disrupts gut barrier and promotes the translocation of bacteria to liver, while altered bile acids metabolism affects NKT cells recruitment in liver, forming a pre-metastatic niche and promoting cancer metastasis.