Scientists discover new mechanism by which statins prevent colorectal cancer

Recently, Professor Fang Jingyuan’s team from Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine published a paper online in Nature Microbiology, revealing for the first time the potential mechanism of statin-shaped intestinal microenvironment to prevent colorectal cancer.

Colorectal cancer is a malignancy that progresses slowly by adenoma-adenocarcinoma. Epidemiological statistics show that statins are associated with a reduced risk of colorectal cancer, so understanding the specific mechanism by which statins work can help achieve new breakthroughs in colorectal cancer prevention.

Prevention mechanisms of statins. Photo courtesy of the research team

Through the colorectal cancer cohort study at Renji Hospital, the team showed that statin users had a lower recurrence rate of adenomas, further supporting the epidemiological evidence that statins can prevent colorectal cancer. Next, mice were used to construct a model of spontaneous intestinal tumorigenesis, and it was found that statins could inhibit the formation of intestinal tumors in mice. In order to explore the mechanism behind this preventive effect, researchers use resources and technologies such as clinical trials, clinical specimens, in vitro and in vivo experiments, bacterial mutants, metabolic mass spectrometry, and transcriptional regulation. Atorvastatin was found to regulate the gut microbiota of mice and alter host tryptophan metabolism, leading to the growth of Lactobacillus reuteri. In addition, a clinical trial in volunteers found that the abundance of Lactobacillus reuteri in the subjects’ feces was upregulated after receiving statin therapy.

The researchers pointed out that the protective effect of Lactobacillus reuteri may be caused by tryptophan metabolites produced by the bacteria, and to further confirm this conclusion, the authors constructed a mutant strain of Lactobacillus reuteri, which greatly weakened the ability of intestinal tumor formation in mice, and inhibited the occurrence of colorectal cancer by binding and antagonizing its transcriptional activity through transcription factors of cell differentiation.

This study reveals for the first time that the gut microbiota is the basis of statin chemoprevention, and proposes that single commensal bacteria or their metabolites can be used as a supplement to current colorectal cancer prevention strategies, laying a new idea for colorectal cancer chemoprevention. (Source: China Science News, Zhang Shuanghu, Huang Xin)

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