Monday, February 23, 2009

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

7 comments:

Anna said...

The phrase that comes to mind is "can't see the forest for the trees".

Reminds of people who won't use table sugar, maple syrup, or honey because of the glycemic index, but load up on agave syrup on a daily basis instead.

Thackray said...

Peter,

The chylomicrons package the long chain fatty acids in the small intestine. So how does the bacteria in the small intestine differ from the large intestine? I take it that the researchers are referring to gram negative anaerobic bacteria?

As you have mentioned before, the makeup and quantity of anaerobic bacteria in the large intestine is influenced by the availability of fermentable carbohydrates. What influences the bacteria types and concentrations in the small intestine?

From what you have stated before, a human carnivore should not be heavily colonized with anaerobic bacteria. So maybe AGAIN, the problem is long chain fatty acids in combination with carbohydrates?

Our chickens are laying well now!! Hope yours are doing fine!

Regards,

Philip Thackray

Peter said...

Yes, the SI bacteria will be influenced by the dysbiosis which will be present in an overweight American or a mouse on lab chow. What is normal is not up for study at the moment. But some endotoxin uptake looks normal to me as this seems to be hat keeps the immune system working correctly. Once you mangle the immune system (Hypovitaminosis D, omega six excess, high sucrose intake...) the response to endotoxin may then become pathological

Peter

Eight eggs per day is the current average but one day we had 11 eggs from 10 chickens... Doing well!

ItsTheWooo said...

In summary, a moderate amount of endotoxin is good, but excessive amounts or too little is lethal. I suppose this makes sense; excessive amounts of endotoxin would only ever occur during overwhelming infection (an unnatural circumstance) or after being sterilized with antibiotics (another unnatural circumstances). The immune system can only cope with what it was genetically instructed to cope with after all...


Regarding intestinal dysbiosis I've observed that when I start gaining weight (indicating and causing metabolic/immune system dysfunction) then immediately I start having difficulties with abdominal bloat, gas, bad breath so on. When I restrict calories and go borderline ketogenic for a few days, everything gets back in order. I wonder if this calorie restriction and borderline ketotic dieting starves gut bacteria and may be partially responsible for the normalizing of bloat/gas/breath.

Sometimes I wonder if there is a relationship between my emotional malaise and the gut bacteria issues when eating less strictly and gaining weight.

Óscar said...

I know t's an old thread but came here after searching for LPS after eading this: http://www.dovepress.com/comparison-with-ancestral-diets-suggests-dense-acellular-carbohydrates-peer-reviewed-article-DMSO

What's your opinion on the theory?

Óscar said...

I know t's an old thread but came here after searching for LPS after eading this: http://www.dovepress.com/comparison-with-ancestral-diets-suggests-dense-acellular-carbohydrates-peer-reviewed-article-DMSO

What's your opinion on the theory?

Peter said...

It's interesting but I can't see where, from the abstract, he links the microbiota/LPS to spontaneous appetite normalisation on LC eating. Surely this should maximise endotoxin absorption? Though it is quite possible that w/o fat endotoxin is still absorbed, it just goes straight to the liver...

I also see ageing of the electron transport chain as crucial to the irreversibility of the changes induced by modern diets. I see plenty of people describing health on all sorts of macro nutrient ratios but I'm quite cautious that these are real in terms of mitochondrial health. I find it difficult to see reversal of oxidatively damaged mitochondria. Side step the damage with LC or high exercise and you have still just side stepped the problems...

Peter