Changes in Gut and Plasma Microbiome following Exercise Challenge in ME/CFS

[msf]

This kind of finding will substantiate leaky gut theory. Definitively if its repeatedly and independently replicated. However it might show that the problem is transient, and has triggers, rather than continuous.

Well, they need to test the total levels of these bacteria at rest in both ME patients and controls.

 

[jimells]

Yes, as has been said before, exercise increases intestinal permeability.

I get PEM long before my activity levels reach that of "exercise", and so do many others.

 

[ScottTriGuy]

Yes, as has been said before, exercise increases intestinal permeability.

I'd assumed it went the opposite way - in the triathlon-geek world the mantra is 'as exercise intensity increases, calorie absorption decreases' - so I'm just extending that thought to permeability.

 

[John Mac]

I get PEM long before my activity levels reach that of "exercise", and so do many others.

It depends on what you mean as exercise. If walking to the bathroom causes PEM then that's exercise for you.
I would guess the patients volunteering for this trial were on the mild side.

 

[jimells]

Yes, as has been said before, exercise increases intestinal permeability.

Do we know specifically what it is about "exercise" that increases permeability? An increase of lactate or some other product of cell metabolism?

 

[Simon]

What do some of our thinkers think of this? @Jonathan Edwards @alex3619 @Simon @Bob

Don't know about 'thinker' but I've had a quick look. Few comments:

• with such a small sample size it's hard to draw any conclusions, other than 'this looks interesting, worth repeating'
• however most things they looked at weren't significantly diff between patients and controls, and this may be a false positive, esp as they didn't seem to correct for multiple comparisons. Replication is everything
• The patients were pretty fit at VO2 mx of 28 ml/Kg/min for avg age 49, the same as controls (avg age 46). Patient fatigue didn't increase as much as I'd have expected for a maximal test, though maybe that's related to the higher level of fitness. And the post-test fatigue pattern was v diff in patients than controls

 

[adreno]

Do we know specifically what it is about "exercise" that increases permeability? An increase of lactate or some other product of cell metabolism?

Not sure if the exact mechanism is known. There have been quite a few studies on this, you are welcome to do a review of the data. It would be interesting to know more about this.

 

[A.B.]

The patients were pretty fit at VO2 mx of 28 ml/Kg/min for avg age 49, the same as controls (avg age 46). Patient fatigue didn't increase as much as I'd have expected for a maximal test, though maybe that's related to the higher level of fitness. And the post-test fatigue pattern was v diff in patients than controls

That's good news. If the abnormality is seen even in mildly affected patients, then it's more likely to be a good biomarker candidate. At least that's how I see this.

 

[Gijs]

The important fact is that abnormalities showing themselves after exercise. This is the hallmark of this disease and every study must be done before and after exercise.

 

[msf]

Don't know about 'thinker' but I've had a quick look. Few comments:

• with such a small sample size it's hard to draw any conclusions, other than 'this looks interesting, worth repeating'
• however most things they looked at weren't significantly diff between patients and controls, and this may be a false positive, esp as they didn't seem to correct for multiple comparisons. Replication is everything
• The patients were pretty fit at VO2 mx of 28 ml/Kg/min for avg age 49, the same as controls (avg age 46). Patient fatigue didn't increase as much as I'd have expected for a maximal test, though maybe that's related to the higher level of fitness. And the post-test fatigue pattern was v diff in patients than controls

When you say ´most things weren´t significantly different´ are you including the increase in the 6 out of 9 genera of bacteria? Because that seems to be the significant finding.

 

[Bob]

I've only had a glance at this study so far. Contrary to initial impressions, figure 2 seems to suggest that changes in blood bacteria is less of a potential issue in patients than in healthy controls. And if you compare figure 2 with figure 3, then figure 3 doesn't seem so dramatic or interesting. Is there anything to suggest that the changes in blood bacteria levels is caused by gut permeability rather than differences in immune function related to exertion? I can't see any evidence to suggest that. And figure 2 even suggests less gut permeability in patients on an ongoing basis. But I've only glanced at it - I'll read more later.

 

[msf]

Wouldn´t they be the same thing? Doesn´t immune function determine intestinal permeability?

 

[MeSci]

Not sure if the exact mechanism is known. There have been quite a few studies on this, you are welcome to do a review of the data. It would be interesting to know more about this.

I raised this in my first blogpost, and it is a subject that interests me greatly. (Probably not everything in that post is right, but I was fumbling my way towards finding a solution, and throwing out ideas for discussion and consideration.)

As I said in that blogpost, a paper describing how exertion can increase intestinal permeability can be read here. And that was in athletes.

Interesting that the microbiome can affect susceptibility to influenza (EDIT - referring to @Kati's linked paper). I have recently been in hospital, where they gave me an antiviral and an antibiotic. Probable consequence - liquid diarrhoea - a messed up gut, and now I have the first bad cold or flu I have had for many years.

I think @alex3619 is right when he says that it is not (EDIT - usually?) bacteria that cross the gut epithelium. It commonly includes lipopolysaccharides (LPS), doesn't it?

 

[Simon]

When you say ´most things weren´t significantly different´ are you including the increase in the 6 out of 9 genera of bacteria? Because that seems to be the significant finding.

Yes, that was significant, but note that it seems this was run as a single experiment: one p value compares the changes over time across nine genera in patients vs controls. I'm not sure how many of the individual genera would have been significant on their own. Basically Im saying this still looks like an interesting study but with only ten patients and ten controls we shouldnt get too excited - yet.

 

[geraldt52]

This might be a stupid question, but could this explain why people tend to respond to antibiotics, at least over the short term, but they never really "cure" anything?

 

[MeSci]

Wouldn´t they be the same thing? Doesn´t immune function determine intestinal permeability?

I think, that as with most things in biology, there tends to be a dynamic interaction between several things: epithelium, diet, microbiota, immune cells, maybe vagus nerve, etc.

 

[ahmo]

I have recently been in hospital, where they gave me an antiviral and an antibiotic. Probable consequence - liquid diarrhoea - a messed up gut, and now I have the first bad cold or flu I have had for many years.

 

[Bob]

This might be a stupid question, but could this explain why people tend to respond to antibiotics, at least over the short term, but they never really "cure" anything?

I was thinking that too, so that's two of us asking stupid questions! Or perhaps it's a really smart question?!

 

[msf]

Yes, that was significant, but note that it seems this was run as a single experiment: one p value compares the changes over time across nine genera in patients vs controls. I'm not sure how many of the individual genera would have been significant on their own. Basically Im saying this still looks like an interesting study but with only ten patients and ten controls we shouldnt get too excited - yet.

Well, the graphs look significant to me, but then I know nothing about statistics! When one goes from bottom left to top right, and the other from top left to bottom right, that´s good, isn´t it?

Re: the small simple size, it´s a shame that so much research into ME has had this limitation, and then never been reproduced in a larger study - hopefully this finding will be.

I know this isn´t how science works (or how a scientific theory is proven rather), but I see this as corroborating evidence that supports the findings of Maes (IgM to gut bacteria in the blood) and Montoya and Lipkin (daily fluctations in Leptin possibly driven by fluctuations in LPS in the blood). Note also that this study reproduces one of the findings of De Meirleir (firmicutes/bacteriodes ratio) from a study with a much larger sample size.

 

[Simon]

Well, the graphs look significant to me, but then I know nothing about statistics! When one goes from bottom left to top right, and the other from top left to bottom right, that´s good, isn´t it?

With such small samples, these average changes might not be significant (ie individual patients might have quite different patterns, and because of that 'noise', the average difference might well not be significant. Plus, do the changes in proportions have clinical significance?

I'm afraid I don't have any more energyy to spare on this so will leave the thread at this point. I hope this approach is repeated and if the findings replicate, then that could be very interesting.