Fats and absorbing endotoxin

Chris sent me a very interesting link a while ago and it just brought home to me how difficult it is to interpret a study in isolation. In fact, how random the world is in terms of what anyone does or doesn't know.

Bacterial endotoxin is a breakdown product of the cell wall of gram negative bacteria. It's a lipopolysaccharide and even quite small amounts of it are extremely unpleasant. In overwhelming gram negative infections killing the bacteria releases endotoxin which can itself be fatal to the patient. Not killing the bacteria can have the same effect on mortality, so the best advice I can give is to avoid overwhelming infection.

Now the scary thing is that eating a high fat meal, probably based on any fat which generates chylomicrons, markedly increases you uptake of endotoxin from your gut, which is obviously full of gram negative bacteria. Eating short chain fatty acids or carbohydrate does not have this effect.

OK, so the prediction from this research is that eating a diet which generates chylomicrons will produce all sorts of nasty changes in your body. Hmmmmm, well maybe, but I've not noticed.

Then came a fascinating random paper through my wife's journal club meetings, which are a routine part of her PhD. It's about superinfection with resistant bacteria when broad spectrum antibiotics are used. This is a routine problem for anyone in medicine, especially patients. The concept is very simple, you kill off the susceptible commensal bacteria in the gut and resistant pathogens have no competition, so they have a field day and superinfection causes severe problems for the unlucky patient.

Simple, straightforward and wrong.

It turns out that the immune system, that is the innate immune system (of course), continuously monitors the contents of the gut by looking at endotoxin production. Lots of bacteria mean lots of endotoxin and an active, on-guard innate immune system. Kill off 99% of your gut bacteria and exdotoxin production drops. The innate immune system goes on vacation and clostridium difficile gets in and wipes out your granny.

Simple administration of oral endotoxin to the experimental mice stopped this effect completely.

So yes, it looks like chylomicrons carry endotoxin. Phew. That's better than a clostridium difficile infection!

Reminds me of Uffe Ravnskov's paper on the benefits of LDL cholesterol in gram negative septicaemia. Must dig it out for an airing.

Peter