Bile and Intestinal Bacteria

The physiologic utility of bile in the digestive process is to solubilize lipids in the small intestine, facilitating their ultimate absorption across the epithelium. This detergent-like activity of bile, or more accurately, bile salts, is intrinsically damaging to many bacteria. As you might expect then, bacteria that live and proliferate within the intestine have evolved defense mechanisms to avoid the potentially lethal activity of bile. Moreover, a number of pathogenic enteric bacteria also respond to bile by increasing expression of factors that enhance their disease-producing abilities.

The interactions of bile salts and bacteria have been best studied in a number of Gram-negative bacteria, some of which are commensal and others well known to induce intestinal disease. These include Escherichia coli, Salmonella typhi and enterica, and Vibrio cholerae. Resistance of these bacteria to bile is actually exploited for laboratory diagnosis in that they can be isolated away from other bacteria by growth on medium containing bile salts (e.g MacConkey's agar).

At least three mechanisms have been shown to impart resistance of bacteria to the deliterious effects of bile salts:

• Exclusion of bile salts: The outer membrane of Gram negative bacteria is a phospholipid bilayer, but modified by lipopolysaccharide and Lipid A components that seem to reduce its permeability to bile salts.
• Elimination of intracellular bile salts: Many Gram negative bacteria have efflux pumps that actively excrete bile salts that penetrate both outer and inner membranes.
• Repair systems that are able to fix damage to proteins and DNA within bacteria due to the toxic effects of bile salts.

Another property of many enteric bacteria is the ability to form biofilms in which groups of bacteria secrete and become encased in an exopolysaccharide that decreases access to bile salts.

In addition to resisting the toxic effects of bile, there are numerous indications that bile salts actually stimulate expression of virulence factors in some pathogenic enteric bacteria. For example, enteropathogenic E. coli respond to bile salts with an increased ability to adhere to cells. Conversely, bile acids also appear to play a critical role in regulating intestinal mucosal immune responses.

References and Reviews

• Hay AJ, Zhu J. In Sickness and in Health: The Relationships Between Bacteria and Bile in the Human Gut. Adv Appl Microbiol 2016; 96:43-64.
• Mohammed AD, Ball RAW, Kubinak JL. The interplay between bile acids and mucosal adaptive immunity. PLoS Pathg 2023; 19: e1011356.
• Sistrunk JR, Nickerson KP, Chanin RB, Rasko DA, Faherty CS. Survival of the fittest: How bacterial pathogens utilize bile to enhance infection. Clin Microbiol Rev 2016; 29: 8190836.

Updated July 2023. Send comments to Richard.Bowen@colostate.edu