The autonomic nervous system (ANS) consists of three components: the sympathetic (noradrenergic) and parasympathetic (cholinergic) systems, which originate in the central nervous system; and the enteric system, which lies within the wall of the gastrointestinal tract.
The enteric system, which contains a similar number of neurons as the spinal cord, regulates intestinal functions; this system is modulated by projections from the sympathetic and the parasympathetic systems. The sympathetic nervous system (SNS) sends axons to all parts of the body, and catecholamines (CAs), the end products of SNS, modulate several immune parameters. Thus, lymphoid and non-lymphoid organs are not only extensively hardwired by noradrenergic nerve terminals, but also the immune cells, thereby the immune system is tuned by norepinephrine (NE) released locally from non-synaptic varicosities or circulating epinephrine (adrenaline) secreted by the adrenal medulla. Therefore, the SNS provides a major integrative and regulatory pathway between the brain and the immune system.
The gastrointestinal (GI) tract is extremely sensitive to stress and stress mediators, including CAs. In humans, changes in the gut microbiota have been associated with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), conditions in which stress is well-known risk factor. The SNS and particularly stress-induced hyperactivity of the SNS, through release of CAs can influence bacterial infections, indirectly, through effects on the immune system. An area that has received much less attention is the direct affect CAs have on bacterial growth. In fact, the ability of enteric bacteria to respond directly to stress-related neuromediators such as CAs, has now been identified as a new mechanism by which stress can influence the bacterial infectivity in a non-immune manner – this mechanism operates at the level of the intestinal mucosa, which represents a complex network of epithelial cells, immunocytes and nerves in direct contact with the external environment. Research extending back to the 1920s had shown that co-administration of epinephrine (adrenaline) along with bacteria resulted in a greatly increased ability of bacteria to cause an infection. Much more recent evidence indicates that CAs can dramatically increase the growth, for example of Gram-negative bacteria such as Escherichia coli and Yersinia enterocolitica, and the demonstration that this effect was due to a direct interaction with bacteria was shown in a series of in vitro studies begun in 1992.
In a contemporary review, published in 2011, Mark Lyte, Lucy Vulchanova and David Brown provide a brief but comprehensive overview of the actions of stress mediators, especially CAs, on enteric luminal bacteria, on gut mucosal interactions with bacteria, and on brain–gut interactions initiated by or influencing enteric bacteria. The authors recapitulate recent evidence indicating that NE, released within the intestinal wall during activation of the SNS in acute stress, has a wide variety of actions at the intestinal mucosa.
The major topics and issues discussed by the authors include:
- Direct effects of stress mediators on enteric bacteria
- Cellular targets of stress mediators in the intestinal mucosa
- Effects of stress mediators on host epithelium interactions with microbes
- Intestinal bacteria and the gut-brain axis
The information summarized in this overview indicates that stress-mediated changes in the delicate GI mucosal interactions with enteric bacteria may shift the microbial colonization patterns on the mucosal surface and alter the susceptibility of the host to infection. Thus, the authors of this review identify new mechanisms by which stress may influence both health and disease states of the digestive tract.
SOURCE: Cell Tissue Res 2011, 343:23. Epub 2010 Oct 13.