Gut bacteria in health and disease

Abstract

A new era in medical science has dawned with the realization of the critical role of the "forgotten organ," the gut micro-biota, in health and disease. Central to this beneficial interaction between the microbiota and host is the manner in which bacteria and most likely other microorganisms contained within the gut communicate with the host's immune system and participate in a variety of metabolic processes of mutual benefit to the host and the microbe. The advent of high-throughput methodologies and the elaboration of sophisticated analytic systems have facilitated the detailed description of the composition of the microbial constituents of the human gut, as never before, and are now enabling comparisons to be made between health and various disease states. Although the latter approach is still in its infancy, some important insights have already been gained about how the microbiota might influence a number of disease processes both within and distant from the gut. These discoveries also lay the groundwork for the development of therapeutic strategies that might modify the microbiota (eg, through the use of probiot-ics). Although this area holds much promise, more high-quality trials of probiotics, prebiotics, and other microbiota-modifying approaches in digestive disorders are needed, as well as laboratory investigations of their mechanisms of action.

Keywords: Gut flora; gut bacteria; microbial metabolism; microbiota; mucosal immunology; probiotic.

Figure 1

A schema to summarize the possible role of the microbiota in irritable bowel syndrome. An altered microbiota in concert with a leaky epithelial barrier allows bacteria and/or bacterial products access to the submucosal compartment where mast cells and immune cells (lymphocytes) are activated, releasing mast cell proteases, chemokines, and cytokines, which can activate sensory neurons. This, in turn, can result in local reflexes that affect motor and secretory functions or lead to enhanced visceral sensation centrally.

Figure 2

The gut flora (microbiota) and the liver. Small intestinal bacterial overgrowth (SIBO), present in a variety of liver diseases, and/or an altered composition of the colonic microbiota lead to an enhanced release of proinflammatory cytokines. Increased intestinal permeability, also well described in liver disease, enhances translocation of bacteria, endotoxin, or proinflammatory products such as lipopolysaccharide (from gram-negative bacteria), which reach the liver through the portal vein or, in the presence of portal-systemic shunting, access the systemic circulation directly.