PDF (3.6 MB)
Collect
Submit Manuscript
Show Outline
Outline
Abstract
Keywords
Electronic Supplementary Material
Show full outline
Hide outline
Research Article | Open Access | Just Accepted

High dietary methionine induces secondary bile acids dysmetabolism and promotes the development of colorectal cancer in mice

Wanhua LiAiying ShiXiaoxia LiuYunhui ZhangYingshuang LuLu DongJin WangYan Zhang()Shuo Wang()

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China

Show Author Information

Abstract

Methionine, an essential amino acid, is abundant in animal protein. High dietary methionine intake is associated with the promotion of colorectal cancer (CRC); however, the mechanisms remain unclear. This study aimed to investigate the underlying mechanisms of high dietary methionine promoting CRC and evaluate the effect of high dietary methionine on healthy intestine. Our results demonstrated that high dietary methionine intake exhibited a higher incidence and invasion of tumors in AOM/DSS-induced mice. Meanwhile, the gut microbiota were disturbed, consequently fostering the metabolism of secondary bile acids. The contents of lithocholic acid (LCA) and deoxycholic acid (DCA) significantly increased (P < 0.01), which further activated the bile acid membrane receptors TGR5, and then the activated TGR5 promoted tumor proliferation through STAT3 and YAP pathways. Pseudo-germ-free mice validate the role of gut microbiota and secondary bile acids in promoting CRC by high dietary methionine. Notably, similar disturbances in gut microbiota and bile acid metabolism were observed in the intestine of healthy mice with high dietary methionine intake. In conclusion, dysregulation of bile acid metabolism and activation of the corresponding receptor TGR5 were mechanisms promoting CRC associated with high dietary methionine intake.

Electronic Supplementary Material

Download File(s)
2023-00230.R2_ESM.docx (2.2 MB)
Food Science and Human Wellness
Cite this article:
Li W, Shi A, Liu X, et al. High dietary methionine induces secondary bile acids dysmetabolism and promotes the development of colorectal cancer in mice. Food Science and Human Wellness, 2024, https://doi.org/10.26599/FSHW.2024.9250237
Metrics & Citations  
Article History
Copyright
Rights and Permissions
Return