Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon

Abstract

Western-style diets (WD) high in fat and scarce in fiber and vitamin D increase risks of colorectal cancer. Here, we performed a long-term diet study in mice to follow tumorigenesis and characterize structural and metabolic changes in colon mucosa associated with WD and predisposition to colorectal cancer. WD increased colon tumor numbers, and mucosa proteomic analysis indicated severe deregulation of intracellular bile acid (BA) homeostasis and activation of cell proliferation. WD also increased crypt depth and colon cell proliferation. Despite increased luminal BA, colonocytes from WD-fed mice exhibited decreased expression of the BA transporters FABP6, OSTβ, and ASBT and decreased concentrations of secondary BA deoxycholic acid and lithocholic acid, indicating reduced activity of the nuclear BA receptor FXR. Overall, our results suggest that WD increases cancer risk by FXR inactivation, leading to BA deregulation and increased colon cell proliferation. .

Rebuilding the Gut Microbiota Ecosystem

“…in their gut microbiota, while diets rich in plant polysaccharides are associated with increased amounts of Prevotella spp. [51]. Elevated dietary intake of fat meals impacts bile acid homeostasis and colon tumorigenesis [51].…”

“…[51]. Elevated dietary intake of fat meals impacts bile acid homeostasis and colon tumorigenesis [51]. The gut microbiota is able to metabolize these compounds and converts primary bile acids (cholic acid and chenodeoxycholic acid) into secondary bile acids (deoxycholic acid and lithocholic acid) by a C-7 dehydroxylation.…”

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

“…On the contrary, high calorie intake such as consumption of high fat diet readily promotes intestinal epithelial proliferation, in turn increasing the risk of tumorigenesis. [ 189 ] Therefore, the metabolites produced by gut microbiota at the respective energy states seem to exert effects on intestinal stem cells and corroborate with typical stem cell behavior during that phase. Consequently, we speculate that gut microbiota‐derived metabolites could act as second messengers to modulate host intestinal stem cell activity in line with host energy demand.…”

Synbiotic Combination of Djulis (Chenopodium formosanum) and Lactobacillus acidophilus Inhibits Colon Carcinogenesis in Rats

“…Previous studies pointed out that dietary pattern could significantly affect the risk of cancer [2]. Western diet, a diet high in fat and low in dietary fiber, increases the risk of CRC [3].…”