Role of Bile Acids and Gut Microbiota in Parenteral Nutrition Associated Injury

Abstract

Total Parenteral Nutrition (TPN) is a life-saving therapy where all nutritional requirements are provided intravenously. While this therapy is essential for individuals unable to process their nutritional needs enterically, significant complications arise such as intestinal failure associated liver injury (IFALD). IFALD includes hepatic steatosis, cholestasis, inflammation, ultimately progressing to cirrhosis and portal hypertension and some patients may need liver transplantation. The exact mechanism underlying this condition is not well understood, but studies have recently suggested that changes in gut microbiota and intraluminal bile acid signaling are known to play a role in the development of IFALD. In enterohepatic circulation with normal enteral nutrition, gut Farnesoid X Receptor (FXR) is activated by bile acids, which triggers the release of Fibroblast Growth Factor 19 (FGF19) into portal circulation. FGF19 serves to regulate intrahepatic bile acid synthesis with enteric nutrition. This signaling pathway is impaired in TPN as studies indicate decreased serum levels of FGF19 in subjects receiving TPN. Finally, gut microbiota is severely altered in TPN due to intestinal hypomobility. The shift in gut microbiota affects our immune response and promotes endotoxins that negatively affect liver function. Targeting the pathways affecting gut microbiota and bile acid signaling has promise in treating TPN associated injuries.

Keywords: CDCA: Chenodeoxycholic acid; DC: Duodenal catheters; FGF19: Fibroblast growth factor 19; FXR: Farnesoid x receptor; TPN: Total parenteral nutrition, Bile acid.