The causes of intestinal dysbiosis: a review

Alternative Medicine Review, June, 2004 by Jason A. Hawrelak, Stephen P. Myers

In vitro experiments performed by Lyte et al showed exposure of enterotoxigenic and enterohemorrhagic strains of E. coli to norepinephrine resulted in increased growth and the expression of virulence factors, such as the K99 pilus adhesin, which is involved in the attachment and penetration of the bacterium into the host's intestinal mucosa. Growth of the enterohemorrhagic E. coli was also increased, as was its production of Shiga-like toxin-I and Shiga-like toxin-II. The capability of norepinephrine to enhance both bacterial virulence-associated factors and growth was shown to be non-nutritional in nature--in other words, the bacteria did not use norepinephrine as a food; rather, the effect was via an unknown mechanism. (68)

Additional experiments by Lyte et al demonstrated that upon exposure to norepinephrine, E. coli produces a growth hormone known as an "autoinducer of growth." (69) This autoinducer showed a high degree of cross-species activity with other gram-negative bacteria, resulting in increased growth of other organisms. It was later found to stimulate 10- to 104-fold increases in the growth of 12 of 15 gram-negative microorganisms tested. (70)

Exposure to stress has been documented to result in dramatic and sustained increases in catecholamine levels. This high concentration of catecholamines, and especially norepinephrine, may result in increased growth of PPMs in the intestines. (61) The GIT has abundant noradrenergic innervation and a high amount of norepinephrine is present throughout. (71) Studies conducted by Eisenhofer et aL showed 45-50 percent of the total body production of norepinephrine occurs in the mesenteric organs. (72,73) Lyte suggests spillover of norepinephrine into the lumen of the intestinal tract undoubtedly occurs due to the concentration gradient present within the mesenteric organs. (74) Thus, there would be no requirement for an active transport system. This spillover effect has previously been demonstrated for serotonin following its release from gut enterochromaffin cells. (75) As such, the GIT represents an area in which neuroendocrine hormones like norepinephrine coexist with indigenous microflora. (74) Thus far, catecholamines have not been found to induce the growth of gram-positive bacteria. (70)

The effect of norepinephrine on gut flora was recently demonstrated in a murine model. The release of norepinephrine into the systemic circulation, caused by neurotoxin-induced noradrenergic neuron trauma, resulted in increased growth of gram-negative bacteria within the GIT. The total gram-negative population increased by 3 log units within the cecal wall and 5 log units within the cecal contents inside a 24-hour time period. The predominant species of gram-negative bacteria identified was E. coli. (74)

To summarize, stress can induce significant alterations in GIT microflora, including a significant decrease in beneficial bacteria such as Lactobacilli and Bifidobacteria and an increase in PPMs such as E. coli. These changes may be caused by the growth-enhancing effects of norepinephrine on gram-negative microorganisms or by stress-induced changes to GIT motility and secretions.