Bacterial growth – effects of catecholamines on digestive health
In a contemporary review, published in Cell and Tissue Research, 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 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. Thus, incubation of enteric bacteria, such as the Gram-negative bacteria Y. enterocolitica and Escherichia coli, in the presence of NE results in a logs-fold increase in the catecholamine-exposed bacteria as compared to non-catecholamine treated control. 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.
The authors of the Cell and Tissue Research article 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
In conclusion, the authors discuss that the microbiota contained in the gut represent nearly 95% of the total cellular population contained within an individual mammalian host, and its interaction with epithelial-neural-immune elements within the intestinal tract is increasingly being viewed as an emerging interdisciplinary field of considerable biomedical importance.
It appears that the sympathetic neural activity can produce at least short-term changes in microbial colonization of the mucosal surface. 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.
Updated
A 2023 study by Lingdi Niu et al. determined whether enterotoxigenic Escherichia coli (ETEC)-catecholamine hormone interactions contribute to the development of diarrhea. They tested the effects of catecholamine acting on ETEC in vitro.
Background: In developing countries, enterotoxigenic Escherichia coli (ETEC) is a significant contributor to diarrhea in children. Norepinephrine (NE) and epinephrine (Epi) have a good growth-promoting effect on most bacteria, including Listeria monocytogenes, Streptococcus pneumoniae, Aeromonas hydrophila, Campylobacter jejuni, and various Vibrio spp.
The results showed that in the presence of norepinephrine (NE) and epinephrine (Epi), the growth of 9 out of 10 ETEC isolates was promoted, the MICs of more than 60% of the isolates to 6 antibiotics significantly increased, and the biofilm formation ability of 10 ETEC isolates was also promoted. In addition, NE and Epi also significantly upregulated the expression of the virulence genes feaG, estA, estB, and elt.
The authors concluded that when exposed to catecholamine hormones, ETEC would show an increase in the growth, antimicrobial susceptibility, biofilm formation ability, and gene expression of ten ETEC isolates, and this may be related to the fact that NE regulates the genes associated with it. These data demonstrated that catecholamine hormones may augment the diarrhea caused by ETEC.
A 2019 review by Emmanuel Sarkodie et al. provided a brief but comprehensive synopsis on the interaction of gut bacteria with the stress hormones and neuromediators, or the catecholamines epinephrine (Epi), norepinephrine (NE) and dopamine (Dopa).
This includes the catecholamine effects on the growth and virulence of bacteria. Of note, as outlined by the authors, most investigations of catecholamine growth effects have been conducted in vitro using serum- or blood-containing culture media. Thus, catecholamines including NE, Epi, and Dopa, directly influence the growth of Gram-negative bacteria, such as E. coli, Yersinia enterocolitica, and Pseudomonas aeruginosa.
Interestingly, the growth-stimulating effect of catecholamines has been primarily related to the catechol-containing moiety forming a building complex with the iron within beta globulin or lactoferrin (Lf), which weakens iron (Fe) binding and so enables bacteria to acquire the normally inaccessible complexed vertebrates and invertebrates.
In terms of bacterial catecholamine receptors, there is so far no genomic evidence for the existence of a classical adrenergic receptor motif in bacterial species. As per the work of Clarke et al., NE is able to bind to the E. coli O157: H7 two-component regulator sensor kinase QseC, leading to the hypothesis that QseC is the bacterial catecholamine receptor.
Although genomic analyses reveal no adrenergic and dopaminergic receptors in bacteria, the authors referred to studies finding that adrenergic and dopaminergic antagonists block NE, Epi, and Dopa responsiveness in both Gram-negative and -positive bacteria. And, intriguingly, only α-adrenergic antagonists, but not β-adrenergic antagonists, block bacterial responses to NE and Epi. For more information, see the review by Emmanuel Sarkodie et al.
Importantly, different bacteria respond differently when exposed to catecholamines. Gram-negative bacteria are more responsive to the growth-enhancing effects of catecholamines than Gram-positive bacteria. The siderophores and the ferric iron transport system plays a vital role in the mechanism by which catecholamines stimulates growth and exposure of genes to stress hormones affecting the expression of genes involved in bacterial virulence. The specific systems of norepinephrine, epinephrine, and dopamine, are needed for the essential growth of bacteria.
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