See the links at the bottom of the article if you haven’t been following along, they are in some kind of sequence…
Endotoxin – Product of some bacteria structure known to cause inflammation. Also known as lipopolysaccharide and abbreviated to LPS. Part of gram negative bacteria cell wall. (Article)
CD14 – A protein involved detection of endotoxin.
TLR4 – A protein involved detection of endotoxin.
TLR2 – A protein involved detection of endotoxin.
MyD88 – A protein involved detection of endotoxin.
NFKB – Protein involved in genetic transcription changes in response to stress.
LBP – Lipopolysaccharide binding protein. Binds endotoxin after detection.
The sequence of detection to inflammation is (partially)
TNF/TNFa > Inflammatory cytokine
IL-1b > Inflammatory cytokine linked to pain
IL-6 > An inflammatory cytokine and an anti-inflammatory myokine.
Il-8 > Inflammatory cytokine
iNOS > An enzyme catalysing the production of nitric oxide, induced by cytokines.
COX > Cyclooxygenase, a family of enzymes involved in the formation of prostaglandins.
Hypothyroidism slows intestinal transit time. Longer transit time is associated with SIBO (small intestinal bacterial overgrowth). Normal motility of the small intestine may prevent or reverse SIBO. The antibiotic Rifaximin and the probiotic B.Clausii both show improvements in about half of people with SIBO, as measured by SIBO breath tests.Combination of antibiotic followed by probiotic improves outcomes to about 80%, though it’s not clear if this is sustained. Ref
There is an association with inflammatory liver problems and SIBO. In patients with non-alcoholic steatohepatitis (NASH) rates of SIBO are more than double the average (78& vs 31%). The SIBO state can increase permeability and therefore liver and plasma endotoxin, which is a cause of NASH. Ref
Intravenous endotoxin administration to humans causes an increase in reverse T3, and a decrease in plasma T4, free T4, T3 and TSH. These changes were not prevented by blocking TNF via recombinant TNF receptor IgG fusion protein. Ref Ref +
Endotoxin, through the inflammatory cytokine response, lowers the liver conversion of T4 to the metabolically active thyroid hormone T3. This is a cause of “euthyroid sick syndrome, that is, low plasma T3 concentration with an “inappropriately normal” TSH. Ref
In the brain a similar enzyme to the one referred in the previous paper is increased, causing local thyrotoxicosis and possibly implaicted in central hypothyroidism through feedback inhibition. Ref
Correcting thyroid function improves dyspepsia, associated with SIBO via lowered rate of intestinal transit time. Ref
Estrogen treated rodents show double the levels of inflammatory cytokines in response to endotoxin. Nitric oxide synthase is increased in endotoxin + estrogen treated animals over endotoxin alone. Changes in intracellular calcium in kuppfer cells is induced by endotoxin, it’s induced by a much smaller dose of endotoxin when estrogen is higher. Estrogen increases the sensitivity of endotoxin sensing proteins. Ref
Previously I looked at the interaction with some B Vitamins ( Here ). It’s worth noting that these come into play directly regarding estrogen and endotoxin as “riboflavin and thiamine are essential in the metabolism of estradiol by liver slices. The inactivation of estradiol is dependent upon the concentration of these vitamins in the liver.” Ref
Progesterone significantly inhibits endotoxin induced IL-6. Ref
Progesterone may protect against endotoxin induced loss of pregnancy. Ref
Progesterone downregulates endotoxin induced increases in nitric oxide. Ref
Progesterone blunts endotoxin induced increases in TLR4 and TNFa. Ref
In cells melatonin inhibits endotoxin induced increases in TLR4 TNF-α, IL-1β, IL-6, IL-8, and IL-10, while melatonin significantly attenuated LPS-induced upregulation of cyclooxygenase (COX)-2 and inducible nitric oxide synthase. Ref
Melatonin mitigates endotoxin induced lung damage. Ref
Pre-treatment with DHEA lowered the TNF response in endotoxin dosed rodents. A dose of endotoxin that killed 95% of controls was fatal to only 24% of DHEA treated animals. DHEA also blunted endotoxin induced increases in serum corticosterone. Ref
DHT blunts endotoxin induced increases in COX-2, TLR4 and inflammatory cytokines. It protects from endotoxin or hypoxia induced vascular injury by attenuating reactive oxygen species. Ref
Endotoxin related articles and podcasts
Biocast 8 – Hello Endotoxin, My Old Friend (Podcast)
Biocast 9 – Endotoxin, Obesity and Diabetes (Podcast)
Biocast 10 Endotoxin Obesity and Diabetes in Humans (Podcast)
Biocast 011 Endotoxin and Dementia (Podcast)
Biocast 12 – Endotoxin, Serotonin, and Depression
Biocast 13 – Serotonin and Anxiety
Biocast 14 – Serotonin, Stress, and Autism