Interactions between Bacteria and Bile Salts in the Gastrointestinal and Hepatobiliary Tracts

Abstract

Bile salts and bacteria have intricate relationships. The composition of the intestinal pool of bile salts is shaped by bacterial metabolism. In turn, bile salts play a role in intestinal homeostasis by controlling the size and the composition of the intestinal microbiota. As a consequence, alteration of the microbiome-bile salt homeostasis can play a role in hepatic and gastrointestinal pathological conditions. Intestinal bacteria use bile salts as environmental signals and in certain cases as nutrients and electron acceptors. However, bile salts are antibacterial compounds that disrupt bacterial membranes, denature proteins, chelate iron and calcium, cause oxidative damage to DNA, and control the expression of eukaryotic genes involved in host defense and immunity. Bacterial species adapted to the mammalian gut are able to endure the antibacterial activities of bile salts by multiple physiological adjustments that include remodeling of the cell envelope and activation of efflux systems and stress responses. Resistance to bile salts permits that certain bile-resistant pathogens can colonize the hepatobiliary tract, and an outstanding example is the chronic infection of the gall bladder by Salmonella enterica. A better understanding of the interactions between bacteria and bile salts may inspire novel therapeutic strategies for gastrointestinal and hepatobiliary diseases that involve microbiome alteration, as well as novel schemes against bacterial infections.

Keywords: Salmonella; bile salts; chronic infection; gall bladder; gene regulation; intestinal microbiome; resistance to bile.

Figure 1

(A) Synthesis of the major bile acids of human bile and circulation in the hepatic, biliary, and digestive systems. Bile acids are transformed into bile salts by the association with Na⁺ or K⁺ ions. Primary bile acids are stored in the gall bladder. After food ingestion, bile released into the small intestine contains 5–15 g of bile acids. In the intestine, bile acids are modified by the effect of intestinal microbiota. Both primary and secondary bile acids are reabsorbed in the terminal ileum into the blood stream. Modified from Fontana et al. (3). (B) Bile acids can be conjugated with either glycine or taurine. In this example, cholic acid becomes either taurocholic acid or glycocholic acid after conjugation with taurine or glycine, respectively. (C) Bile acids are amphipathic, and their hydrophobic side associates with the surface of lipid droplets while the polar groups interact with water creating a stable emulsion of small, mixed micelles. Modified from Hofmann (5) and Vander et al. (35).

Figure 2

Salmonella enterica infection pathogenesis. (1) Salmonella infection starts with the ingestion of contaminated food or water. (2) Salmonellae invade intestinal epithelial cells and migrate to the lamina propria. (3) Two types of infection can occur: gastroenteritis and systemic infection. (4) During systemic dissemination, Salmonella colonizes the liver, the spleen, and the bone marrow. (5) From the liver, Salmonella reaches the gall bladder and can cause chronic carriage. (6) Salmonella carriers shed bacteria into the small intestine upon secretion of bile, and feces contain Salmonella cells. Inspired from Ref. (–157).