Secondary Bile Acids and Short Chain Fatty Acids in the Colon: A Focus on Colonic Microbiome, Cell Proliferation, Inflammation, and Cancer

Abstract

Secondary bile acids (BAs) and short chain fatty acids (SCFAs), two major types of bacterial metabolites in the colon, cause opposing effects on colonic inflammation at chronically high physiological levels. Primary BAs play critical roles in cholesterol metabolism, lipid digestion, and host–microbe interaction. Although BAs are reabsorbed via enterohepatic circulation, primary BAs serve as substrates for bacterial biotransformation to secondary BAs in the colon. High-fat diets increase secondary BAs, such as deoxycholic acid (DCA) and lithocholic acid (LCA), which are risk factors for colonic inflammation and cancer. In contrast, increased dietary fiber intake is associated with anti-inflammatory and anticancer effects. These effects may be due to the increased production of the SCFAs acetate, propionate, and butyrate during dietary fiber fermentation in the colon. Elucidation of the molecular events by which secondary BAs and SCFAs regulate colonic cell proliferation and inflammation will lead to a better understanding of the anticancer potential of dietary fiber in the context of high-fat diet-related colon cancer. This article reviews the current knowledge concerning the effects of secondary BAs and SCFAs on the proliferation of colon epithelial cells, inflammation, cancer, and the associated microbiome.

The effect of feed restriction on the fat profile of Santa Inês lamb meat

“…Conversely, the decrease in cholesterol levels is related to lipid metabolism in the liver. Although dietary cholesterol has no significant effects on its serum levels in ruminants, biliary cholesterol is reabsorbed and synthesized from acetate in the intestinal mucosa (Zeng, Umar, Rust, Lazarova, & Bordonaro, 2019). Thus, animals fed less feed (30 and 60% restriction) showed decreased cholesterol synthesis because biliary cholesterol may have been metabolized faster because of the decreased amount of feed absorbed.…”

Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR‐PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria

“…Bile acids (BAs) have been traditionally considered to primarily play an important role in cholesterol homeostasis and fat digestion in the gastrointestinal tract. Recent studies have demonstrated that BAs also act as signaling molecules that participate in multiple endocrine and metabolic activities, including their own synthesis and enterohepatic recirculation, energy and glucose homeostasis, inflammation, and cell proliferation 1‐4 . BAs elicit their regulatory roles mainly via BAs receptors, such as farnesoid X receptor (FXR), a member of the nuclear hormone receptor and Takeda G‐coupled protein receptor 5 (TGR5), a membrane G protein‐coupled receptor 2,5,6 .…”

Gut dysbacteriosis and intestinal disease: mechanism and treatment

“…Mice when fed a diet with deoxycholic acid showed reduced generation of SCFAs and altered microbiota diversity, such as reduction of bacteroides, relative increase of Gammaproteobacteria and certain Firmicutes (Zeng et al . 2019). Bile acids activates reactive oxygen (ROS) and reactive nitrogen (RNS) species production during metabolism, and they can damage DNA, so they have a carcinogenic effect (Li and Cao 2016).…”