Is PEM due to bacterial endotoxins?

As with my previous blogpost on leaky gut, I can't be sure I have all the facts straight, but wanted to put this out there, having been trying to get my ME-slowed brain around it. Please feel free to point out any errors or provide further relevant info or links.

I have been pondering for some time on possible relationships between the symptoms of ME/CFS and the exacerbation of them by incorrect diet and over-exertion.

Many people describe their adverse reactions to various treatments as 'Herxing'. This refers to the Jarisch-Herxheimer reaction (http://www.patient.co.uk/doctor/jarisch-herxheimer-reaction) which can accompany the death of various pathogens, notably spirochaetes (US spelling spirochetes) (http://virology-online.com/Bacteria/Spirochaetes.htm) that cause diseases including Lyme Disease and syphilis. Symptoms and signs include:

  • Malaise
  • Slight-to-moderate pyrexia
  • Flush due to vasodilation
  • Tachycardia
  • Leukocytosis
  • Any existing skin lesions become more prominent

The Patient UK page also states:
Hyperventilation and tachycardia are accompanied by hypertension, and then by a drop in blood pressure due to vasodilation and declining peripheral resistance.
But I have been struck by the marked similarity between the symptoms of the Jarisch-Herxheimer reaction and those of ME/CFS, and have wondered why some people are so sure that they are 'Herxing' and not just suffering an exacerbation of their ME/CFS (e.g. post-exertional malaise/PEM).

There are other pathogens, notably gram-negative bacteria, that can cause similar symptoms when they are attacked by components of the immune system, and release endotoxins:

Symptoms and signs listed here include:

  • Fever
  • Increased capillary permeability
  • Chills
  • (Hemorrhagic) shock
  • Leukopenia followed by leukocytosis
  • Severe diarrhea
  • Altered resistance to bacterial infection
  • Thrombocytopenia

Researcher Michael Maes and others have reported remission of symptoms following the healing of leaky gut. Maes and others do indeed consider bacterial endotoxins to be causal factors for ME symptoms. In this paper to which I refer in my earlier blogpost here Maes and Leunis relate symptoms to translocation of bacteria and/or their endotoxins across the gut wall (from the gut lumen to the bloodstream).

So if a person has leaky gut, there will be a more-or-less continuous flow of bacteria and/or their endotoxins (LPS) across the gut wall, and continuous triggering of the immune system to attack the bacteria. Perhaps this continuous immune activity is a significant cause of ME/CFS symptoms. In 'normal' disease (e.g. colds and flu), symptoms tend to be mostly due to our own immune response rather than to the direct activity of the pathogens.

Why do symptoms worsen after exertion, and why is there a delay of one, two, three or even more days before the symptoms appear?

This paper, also cited in my aforementioned blogpost, describes how the gut wall becomes more permeable as a result of exertion - even in healthy people.

The immune system will then attack the (presumably increased) intruding bacteria, causing them to release endotoxins.

This paper found that exertional heat stress caused an increase in endotoxins in the blood of both trained and untrained people. The paper states:

Endotoxin, or LPS, is normally found in large abundance on the surface of gram-negative bacteria in the intestinal lumen. Under physiological conditions, endotoxins are contained and not toxic, since only small amounts enter the circulation from the intestinal lumen and are quickly inactivated by several defense mechanisms. However, failure of the body's defense mechanisms and/or barriers results in substantial endotoxin leakage across the intestinal lumen into the portal and, eventually, the systemic circulation.
I don't know whether the delay in symptoms appearing is due to the time it takes for the gut to become more permeable, the time it takes for the immune system to destroy the bacteria, or both. Maybe observing how soon gut symptoms appear after exertion/dietary error (if one gets gut symptoms) and comparing this with when PEM symptoms appear, can provide a clue.

A leaky-gut-exacerbating diet will cause similar problems. This has indeed been my experience. When my symptoms have become worse, and I have become less tolerant of exertion, I have often been able to link it to a food or a bout of over-exertion (but it's not easy making such links, and much harder if one has made multiple changes around the same time).

As my symptoms have improved, I have noticed that not only does PEM become much milder - at one point almost indetectable - the delay before symptoms appear increases. So when I have been at my best, the PEM was hard to detect, and seemed to be coming about a week after exertion. For most of my illness the delay has been a regular 2 days.

What could this mean? Presumably as my gut is behaving better, fewer pathogenic bacteria and/or their endotoxins are entering my bloodstream thanks to reduced gut wall permeability. Perhaps my immune system is also less active. Perhaps it was previously attacking 'good' gut flora as well as the baddies, exacerbating the gut dysbiosis?

But nothing in biology is simple...

There also seems to be variation according to the season. However well I have paced and eaten, PEM delays start shortening with the days, with symptoms getting slightly worse. As the days are lengthening again, my PEM delay seems to be up to 3 days, and it is getting milder again.

I don't think that this is due to Vitamin D levels, as I use a UVB lamp during the darker times of year.

Scientists are coming to the view that the benefits of sunshine go beyond Vitamin D.

So my prescription is: go and live in the opposite hemisphere when the days are too short in yours! :lol:

(and don't forget the pacing and leaky-gut diet)

UPDATE 18TH JUNE 2014

Have just done 2 more blogposts about PEM and a possible easy way to combat it. Watch me try!

Comments

It is possible!

I took 2 weeks treatment in the clinic detox: starvation, droppers vein to the liver and Vascular, to drive out helminthes, ozone in the vein, ozone in the intestines. Intestinal lavage and sauna #10. Now I feel better
 
I have written about LPS before, and still plan to do a blog on it. LPS is found in our blood. It shouldn't be there unless we have a bacterial infection. So its coming from somewhere. The logical source is the gut. For that to happen, first the gut defenses have to be down, then the liver defenses have to be down. LPS sends our immune system nuts, and can induce migration of immune cells. This raises the question as to whether regular blood tests are reliable if the the culprit cells have migrated to specific areas in the body.
 
"Why do symptoms worsen after exertion..."

Hi, MeSci. For exercise-induced gut permeability, you have to get pretty hot to break down tight junctions. I looked into this 2 summers ago after experiencing it, and in fact was surprised by the high temperatures that the gut gets exposed to during intense exercise on hot days - even higher than what gets measured by oral or rectal thermometer. Part of the reason is intestinal ischemia - when blood flow gets diverted from the gut to the muscles and so gut cooling is reduced.

In your 1st cite, increased intensity creates more heat, as shown on Fig 4. They write, "Because the lactulose-to-rhamnose ratio was not elevated at lower intensities of running, there may be a threshold effect of intensity on small intestinal permeability." From what I've read, people here can get PEM from very low intensity exertion.

In your 2nd cite, the exertion is less but the environment is designed to make the subjects hot: "in a climatic chamber (40°C, 30% relative humidity)".

The trained subjects did better, probably because they upregulate heat shock protein 72 (HSP72) to sort of plug the gaps in the gut as a response to heat.


"Watch me try!" I applaud your approach and the way you use logic. :)
.
.
 
Thanks, Sherlock - interesting info.

Re '"Watch me try!" I applaud your approach and the way you use logic', I'm afraid I failed, and am back to lactic acid/lactate as my theorised cause of PEM (see new post today).
 
MeSci, reading your PEM post of today is what prompted me to notice and read this one.

Did you happen to do one on the exercise used in what is apparently called the PACE trial?
 
I haven't done one, Sherlock, but there are lots of threads on it, and maybe some blogposts.
 
I'm afraid I'm not at all well now, for the last 9 months, so maybe I stopped doing something. I'm not thinking at all well, so having problems working things out.

I'm not healthy-gutted now! I went back on the buckwheat, but am ditching it again. Also back on small amount of oats (in bread) for now.

But my diet and supplements are listed here:

http://forums.phoenixrising.me/index.php?members/mesci.6237/

Good luck!
 

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