Chapter Two - In Sickness and in Health: The Relationships Between Bacteria and Bile in the Human Gut
Introduction
In the gut, trillions of bacteria are kept in balance with the host immune system. Prevention of bacterial outgrowth is coordinated by several immune mechanisms. When a pathogenic bacterium enters this ecosystem, it must also cope with the immune pressure that maintains homeostasis in the gut environment. Bile is one mechanism that functions to maintain this balance that can often be overcome by pathogenic bacteria. Bile is produced by the host as a natural part of digestion but is also major physical barrier that bacteria must cope with, both pathogenic and commensal. In addition to direct antimicrobial killing, bile components have been recently appreciated to play a role in regulation of immune factors that contribute to bacterial control. This review will consider the role that bile plays in protecting the host during health and disease, as well as the ways in which bacteria respond to bile. Particular focus will be given to the mechanisms by which pathogenic bacteria can survive the antimicrobial activity of bile and, in many cases, use this host compound as a signal to coordinate colonization and virulence.
Section snippets
Makeup of Biliary Secretion
Bile is a complex mixture composed of bile acids, bilirubin, cholesterol, phospholipids, fatty acids (both saturated and unsaturated), and ions such as Ca2+, Na+, and Cl− (Hofmann, 1989). The most abundant and most active components in bile are bile acids. Due to the numerous studies of “bile” and component “bile salts” both will be given greater consideration in this review than other bile components. Bile salts are rigid amphipathic molecules with the sterol core. This core is a hydrophobic,
Bile as a Barrier
The intestinal tract is one of the main interfaces between the human body and the microbes that colonize it. Because it comes in contact with both commensal bacteria and potential pathogens, the intestinal tract is an important immune site. This interface consists the intestinal epithelium covered in mucous layers of decreasing density as they extend into the lumen (Johansson et al., 2011). There is dedicated monitoring by immune cells as well as secretion of antimicrobial compounds such as
Bacterial Responses to Bile
For enteric pathogens, it is inevitable that an encounter with bile will occur. Studies examining how bacterial diversification in the gut evolves found that competition for nutrients and presence of bile salts were two of the strongest drivers of selection and diversification (de Paepe et al., 2011). It is not surprising, therefore, that bacteria have developed a myriad of responses to bile and bile salts. For pathogens, these responses can be summarized into four main strategies: exclusion of
Conclusions
While bile is a complex mixture, it is interesting to consider why exposure to different individual bile salts can have drastically different phenotypic outcomes within the same bacteria. One possible reason is that the bile salts can signal directly or indirectly through cellular stress. Bile salts can act as an environmental signal for many pathogens. For example, conjugated bile salts such as taurocholate and glycocholate can initiate growth of spores for C. difficile (Francis, Allen,
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