Relationship with Bile acids and Microbiota

Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. The main function of bile acid is to promote processing of dietary fat. In addition, hepatic synthesis of bile acids is a major mechanism of cholesterol breakdown in the body. Farnesoid-x-receptor (FXR) is known to play a key role in the regulation of bile acid synthesis and homeostasis The large bowel is the most densely populated natural environment known containing roughly 1014 bacterial cells.

Gut Bacteria also produce small chain fatty acids like –Butyrate, Acetate.

Increasing levels of the primary bile acid cholic acid (CA) causes a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa and increasing production of the harmful secondary bile acid deoxycholic acid (DCA). During progression of cirrhosis, the micro biome, both through their metabolism, cell wall components (LPS)and translocation lead to inflammation. Inflammation suppresses synthesis of bile acids in the liver leading to a positive-feedback mechanism. Decrease in bile acids entering the intestines appears to favor overgrowth of pathogenic and pro-inflammatory members of the micro biome including Porphyromonadaceae and Enterobacteriaceae

Decrease in bile acids entering the intestines appears to favor overgrowth of pathogenic and pro-inflammatory members of the micro biome including Porphyromonadaceae and Enterobacteriaceae Decreasing bile acid concentration in the colon in cirrhosis is also associated with decreases in Clostridium cluster XIVa, which includes bile acid 7α dehydroxylating bacteria which produce DCA. Rifaximin treatment appears to act by suppressing DCA production, reducing endo toxemia and harmful metabolites without significantly altering micro biome structure.

Conclusion/Important term The bile acid pool size and composition appear to be a major regulator of microbiome structure, which in turn appears to be an important regulator of bile acid pool size and composition. The balance between this equilibrium is critical for human health and disease. The study of the interaction between bile acids and gut microbiota in the context of liver disease is essential because the human liver is the only organ in the body that produces all 14 enzymes required for de novo synthesis of the primary bile acids.

Questions ?? How effect the concentration of BA on gut Microbiota ? Try to identify the bacterial family which are essential for a good intestinal gut ? More….. Bile Acids: do different dietary lipids lead to/affect bile acid production? Put simply, is there a different production of bile acids with saturated versus unsaturated fats in food?

Is there a different production of bile acids with saturated versus unsaturated fats in food? References: (1997)

Palm oil (rich in long chain saturated fatty acids) Olive oil rich in monounsaturated fatty acids. Corn oil rich in n-6 polyunsaturated fatty acids was studied in vivo in rats fed the corresponding oil in the diet for 21 days.

Olive Oil Corn Oil Palm Oil studied in vivo in rats fed Saturated Unsaturated polyunsaturated Palm Oil studied in vivo in rats fed the corresponding oil in the diet for 21 days

Result and Analysis The initial and final body weights and the final liver weights of the rats.

TG: Triacylglycerol UC: Unesterified cholesterol TC: Total cholesterol

C7aH (nmol/h/mg protein)

Points to connect bile acids and diet feeding mono- or n-6 polyunsaturated as compared to saturated fat in the diet increases the rate of bile acid synthesis in the rat. This conclusion is supported by the finding that the activity of cholesterol 7a hydroxylase, the rate limiting enzyme for bile acid synthesis was higher in the olive and corn oil-fed than in the palm oil- fed rats. In addition, the expression of cholesterol 7a hydroxylase mRNA was markedly increased by the olive oil as compared to the palm oil diet. Increased secretion of cholesterol coupled with a decrease secretion of bile acids causes a rise in the extent to which bile is saturated in cholesterol.

Increase in cholesterol Diet Vs Bile acids Diet Saturated fat Increase in cholesterol Decrease in Bile acids Alter the micro biota Unsaturated fat Increase in Bile acids Healthy Micro biota