Systemic inflammation increases intestinal permeability during experimental human endotoxemia


Senior Member
United States, New Hampshire
Although the gut is often considered the motor of sepsis, the relation between systemic inflammation and intestinal permeability in humans is not clear. We analyzed intestinal permeability during experimental endotoxemia in humans.

Before and during experimental endotoxemia (Escherichia coli LPS, 2 ng/kg), using polyethylene glycol (PEG) as a permeability marker, intestinal permeability was analyzed in 14 healthy subjects. Enterocyte damage was determined by intestinal fatty acid binding protein. Endotoxemia induced an inflammatory response.

Urinary PEGs 1,500 and 4,000 recovery increased from 38.8 +/- 6.3 to 63.1 +/- 12.5 and from 0.58 +/- 0.31 to 3.11 +/- 0.93 mg, respectively (P < 0.05). Intestinal fatty acid binding protein excretion was not affected by endotoxemia. The peak serum IL-10 concentrations correlated with the increase in PEG 1,500 recovery (r = 0.48, P = 0.027).

Systemic inflammation results in an increased intestinal permeability. The increase in intestinal permeability is most likely caused by inflammation-induced paracellular permeability, rather than ischemia-mediated enterocyte damage.

Viral infections cause a significant amount of systemic inflammation. I think this systemic inflammation from viral infections like Epstein Barr virus and other viral infections can cause an increase in intestinal permeability and trigger an immune system reaction from the lipopolysaccharides getting into the bloodstream.

What else can cause systemic inflammation? Any kind of chronic stress or physical stress can. Antibiotics can, of course, cause or contribute to dysbiosis and increased intestinal permeability.

Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion.
Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.

I think the current research of the 4 NIH-funded collaboratives focused on the gut, the brain, the immune system and metabolomics are rate on the money. I think that's where they will get their best answers. Obviously they do too.:)