Low Dose Endotoxemia vs. Chronic Illness and Cognitive Impairment
Understanding the phenomenon of low dose endotoxemia is key to understanding how dysbiosis and low grade infections contribute to so many health conditions; including Dementia, Diabetes, Atherosclerosis, Alzheimers and mild cognitive decline.
Scientists have coined the term “Low Dose Endotoxemia" to describe the phenomenon where the translocation of bacterial endproducts at very low doses into systemic circulation, can stimulate an increase in inflammatory cytokines even in normal healthy people; subsequently producing changes in behaviour and cognitive abilities.
A variety of endotoxins may stimulate production of cytokines, but the one most frequently referred to is LPS - Lipopolysaccharide. component of gram negative bacteria cell wall.
Others include secondary bile acids.
The cytokines and neurotransmitters most associated with illness and cognitive decline include:
IL-6
IL-1 antagonist
TNF-alpha
NFkB
Histamine
Whether or not a low or high concentration of cytokine or neurotransmitter contributes to disease or cognitive impairment is not consistent across all illnesses. For example, in AD cognitive impairment increased in patients with lower TNF-a, but higher histamine and IL-1. Histamine concentration decreased as depression scores increased in the AD patients. The researchers concluded there must be a dysfunction in cytokine and histamine regulation.
How does this happen?
This is more likely to happen if you regularly drink alcohol. Alcohol increases the permeability of the intestinal lining so that larger compounds can pass through than would normally. Such that it is easier for endotoxin to pass through the gut barrier. The more alcohol you drink the greater the degree of circulating endotoxin.
Smoking compromises the epithelial barrier of the lung and increases activation of NFkB; one of the cytokines associated with illness and cognitive decline.
Obesity and high fat diets contribute to increased LPS levels by shifting the bacterial population towards having a higher gram negative count. In obese patients adipose tissue itself secretes pro inflammatory cytokines IL-1B, IL-6 and TNFa. LPS and pro-inflammatory cytokines interfere with insulin signalling creating a self fulfilled prophecy.
Periodontal disease or inflammation around the teeth contributes to circulation of endotoxins from the biofilm producing bacteria.
In patients with intestinal permeability due to dysbiosis endotoxin translocation increases.
How did scientists discover the phenomenon of LDE?
In one study, low dose Salmonella endotoxin was administered to healthy young subjects resulting in negative effects on verbal and non-verbal declarative memory functions and depression score. The different endotoxemia/inflammatory mediators had effect on different cognitive functions. Although, subjects did not experience any of the classical symptoms of regular endotoxemia (constipation, pain, leptin resistance) in these studies, they developed an increase in body temperature of 0.5 °C as well as approximately 100-fold increases in plasma cytokines (TNF-α, IL-6, and IL-1 receptor antagonist.
Keeping in mind that systemic low-grade inflammation is defined by a 2- to 3-fold increase in inflammatory cytokines. These patients were experiencing a 100-fold increase even with very low doses of endotoxin.
Furthermore, the hypothalamo–pituitary–adrenal (HPA) axis was activated which was reflected by elevated levels of cortisol. Chronically elevated cortisol can contribute to symptoms of diarrhea, disrupted sleep, blood sugar dysregulation and weight gain.
Studies in which severely ill patients received cytokines in high doses demonstrated that cytokine administration produced behavioral alterations.
In one study, normal healthy patients were given low dose E-coli endotoxin which resulted in increases in plasma concentrations of TNF-α, sTNF-R, IL-6, and IL-1Ra without activation of the HPA axis. Patients experienced a decrease in memory function.
References
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