Gut Microbiota-Driven Secondary Bile Acid Synthesis Enhances Colorectal Cancer Risk Linked to Western Dietary Patterns

To investigate the role of secondary bile acid production by gut bacteria in colorectal cancer (CRC) associated with Western dietary patterns.

Preclinical Model: Utilized APC 1311/+ pigs to assess the impact of a Western diet on CRC development.
Microbiota Analysis: Conducted multi-omics and cultivation methods to analyze gut microbiota and secondary bile acid production.
Gnotobiotic Mouse Models: Used gnotobiotic mice to demonstrate the effects of specific 7α-dehydroxylating bacteria on bile acid production and tumorigenesis.

Western diet exacerbates colorectal tumorigenesis in APC 1311/+ pigs.
Increased levels of fecal secondary bile acids, particularly deoxycholic acid (DCA), correlate with enhanced epithelial cell proliferation.
Colestyramine administration can reverse the effects of elevated DCA levels.
Colonization of gnotobiotic mice with 7αDH+ bacteria induces DCA production and stimulates colonic epithelial cell proliferation.
7αDH+ bacteria significantly increase colon tumor burden in gnotobiotic CRC models.

The study provides evidence for a role of elevated secondary bile acids, particularly DCA, in Western diet-associated colorectal tumorigenesis.

Findings from animal models may not fully translate to human CRC risk.
The study primarily focuses on specific bacterial strains and their effects, which may not encompass the entire gut microbiome's role.

The results highlight the importance of understanding secondary bile acid production in individuals at risk of CRC.