Reduced diversity and altered composition of the gut microbiome in individuals with ME/CFS

[Farmkeeper]

Here's a summary of the results in Science Daily:

https://www.sciencedaily.com/releases/2016/06/160627160939.htm

 

[Farmkeeper]

From my perspective this is pretty big news. Especially when you consider the source (Cornell University) and the fact that it was funded by the NIH. I'm wondering if this information is going to be shared with the current larger NIH study.

Here is the article: http://www.news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria

A couple things I found interesting:



@Hip I believe that this could back the research that you have found suggesting leaky gut may play a larger role than expected.

I also noticed the reference to "leaky gut." I thought the validity/existence of "leaky gut syndrome" was widely poo-poohed in conventional medicine.

I was surprised to see this side-reference tossed in with no acknowledgement of how controversial it is. I do know that a healthy small intestine is largely bacteria-free, which is why people with small-intestinal bacterial overgrowth (SIBO) are treated with antibiotics.

 

[A.B.]

I also noticed the reference to "leaky gut." I thought the validity/existence of "leaky gut syndrome" was widely poo-poohed in conventional medicine.

I don't know how it's viewed these days but I keep seing research papers talking about bacterial translocation which is just another name for the same thing.

 

[msf]

I also noticed the reference to "leaky gut." I thought the validity/existence of "leaky gut syndrome" was widely poo-poohed in conventional medicine.

I was surprised to see this side-reference tossed in with no acknowledgement of how controversial it is. I do know that a healthy small intestine is largely bacteria-free, which is why people with small-intestinal bacterial overgrowth (SIBO) are treated with antibiotics.

Yes, as A.B. suggests above, I think you have misunderstood. I don´t think any serious doctors question the existence of increased bacterial translocation in some patients, I think they just object to the unscientific term ´leaky gut´, and also perhaps the use of the term by some practitioners without any evidence that the patient in question has increased bacterial translocation.

The small intestine is not largely bacteria-free either, it just has far fewer bacteria than the large intestine.

 

[Kyla]

I also noticed the reference to "leaky gut." I thought the validity/existence of "leaky gut syndrome" was widely poo-poohed in conventional medicine.

I was surprised to see this side-reference tossed in with no acknowledgement of how controversial it is. I do know that a healthy small intestine is largely bacteria-free, which is why people with small-intestinal bacterial overgrowth (SIBO) are treated with antibiotics.

"Intestinal permeability" is the medically accepted term, it basically means the same thing, but the term 'leaky gut' still unfortunately has a hangover of association with pseudoscience

 

[msf]

"Intestinal permeability" is the medically accepted term, it basically means the same thing, but the term 'leaky gut' still unfortunately has a hangover of association with pseudoscience

That´s it!

 

[Hip]

"Intestinal permeability" is the medically accepted term, it basically means the same thing, but the term 'leaky gut' still unfortunately has a hangover of association with pseudoscience

The term "leaky gut" is also used in the medical literature, and is synonymous with the more common medical term "intestinal permeability" as well as a less well used term "intestinal hyperpermeability."



The controversy is not whether leaky gut / intestinal permeability exists — there is no question that it does (you can find over a 1000 papers on PubMed with "intestinal permeability" in the title) — but rather whether leaky gut / intestinal permeability can cause symptoms, or play a role in triggering disease.

The idea or theory that a leaky gut can cause symptoms or play a role in triggering disease is referred to as "leaky gut syndrome," and some alternative health practitioners believe that it can.

The diseases leaky gut syndrome is proposed to cause include ME/CFS, asthma, lupus, rheumatoid arthritis, multiple sclerosis and autism. Ref: 1

In summary: leaky gut is a fact; whereas leaky gut syndrome is an unproven controversial idea.



However, as an ME/CFS treatment, in this 2008 paper, Michael Maes studied 41 ME/CFS patients who he put on "natural anti-inflammatory and anti-oxidative substances, such as glutamine, N-acetyl cysteine and zinc, in conjunction with a leaky gut diet" for a period of 10 to 14 months. Up to 24 patients showed a significant clinical improvement or remission after this protocol, along with attenuation of their IgA and IgM responses to LPS.

So this suggests there may be something to leaky gut syndrome.

In my own case, I started taking a regimen of leaky gut supplements (detailed in this post) for around 9 months. In the last three months of talking this regimen, I noticed major improvements in my ME/CFS.

However, I don't really know if my leaky gut regimen was responsible for this improvement, because in those last three months, I also started taking high dose selenium, which I think was more likely the reason for my improvement.

 

[M Paine]

In previous findings of LPS in blood, and disrupted microbiome, the findings have been spread across multiple papers, each with their own critiques about method, cohort number, case definitions etc. etc.

Leaky gut was still a finding that needed reproduction in patients from a big player, and a well funded study. This is it. Perhaps the other papers carved the way, but this paper is making waves. I've had two friends who don't follow CFS papers forward me a link to this paper. Mainstream Science news is jumping on this paper. Maybe because the Gut Microbiome is hot news... maybe because NIH funded it, who knows. But it's excellent news, and this area needs more attention as it seems like a very promising area of research.

LPS in blood seems like a fairly straight-forward biomarker, does anyone know why that can or can not be used?

 

[Simon]

I also noticed the reference to "leaky gut." I thought the validity/existence of "leaky gut syndrome" was widely poo-poohed in conventional medicine.

Leaky gut was still a finding that needed reproduction in patients from a big player, and a well funded study. This is it.

As far as I can tell, while this study argues for leaky gut/microbial translocation, the only measure of gut permeability they reported found no difference with controls:

If there is damage to the gut mucosa, microbial translocation could increase, altering antimicrobial regulators and dysregulating the innate immune system.

...We also examined … I-FABP as a marker for gastrointestinal tract integrity [21]…

Though the median I-FABP levels in the ME/CFS group was higher than that of the healthy group, the difference was not statistically significant (P = 0.27)…

We also analyzed whether enterocyte damage (i.e., I-FABP levels) was associated with the proposed microbial translocation markers LPS, sCD14, and LBP. We found no relationship between I-FABP and LPS levels (r = −0.125; P = 0.278), I-FABP and sCD14 levels (r = −0.117; P = 0.310), or I-FABP and LBP levels (r = −0.08; P = 0.488)

So that's no evidence for leaky gut using their chosen measure.

The point is that LPS (& related LBP, sCD14 levels) could be elevated for other reason: LPS is released when gram-negative bacteria are present/breakdown - and the body has a system to react because LPS signals danger. But it isn't specific to the gut.

My guess is this also explains why there's no mention of microbial translocation in the title.

 

[aimossy]

Thank you @Simon I was wondering about that specific part of the paper. Really interesting! I had thought this isn't strong for showing leaky gut specifically but there are good things about this paper - in the big picture?

 

[msf]

That´s very conservative of them if that´s true, Simon. I-FABP seems to be more about enterocyte damage than increased permeability per se.

Also, I believe close observation of patients would lead them to conclude that the LPS must be coming from the gut.

 

[ScottTriGuy]

... but this paper is making waves. I've had two friends who don't follow CFS papers forward me a link to this paper. Mainstream Science news is jumping on this paper. Maybe because the Gut Microbiome is hot news... maybe because NIH funded it, who knows. But it's excellent news...

Indeed. I was interviewed yesterday by a reporter for a local paper (Toronto Star) who is doing a story on the study.

She didn't ask me anything specific about the study, only about my experience living with ME. I conveyed in no uncertain terms that we are 'healthcare system victims'. She audibly gasped when I said 'I hope I get cancer' - I then explained about Rituximab / Norway.

 

[Mark]

As far as I can tell, while this study argues for leaky gut/microbial translocation, the only measure of gut permeability they reported found no difference with controls:
So that's no evidence for leaky gut using their chosen measure.

The point is that LPS (& related LBP, sCD14 levels) could be elevated for other reason: LPS is released when gram-negative bacteria are present/breakdown - and the body has a system to react because LPS signals danger. But it isn't specific to the gut.

My guess is this also explains why there's no mention of microbial translocation in the title.

Hanson did note this at IiME: the LPS results were quite strong but interestingly no real evidence of increased permeability.

 

[msf]

There was no real evidence because they only tested one measure of intestinal permeability. I-FABP is not raised in obese people either, from what I´ve just read.

 

[Mark]

There was no real evidence because they only tested one measure of intestinal permeability. I-FABP is not raised in obese people either, from what I´ve just read.

I expect there are other measures that would be interesting to look at; I think this is the only one they looked at as you say. I think they said this is the one that that's elevated in IBS, thus demonstrating that the elevated LPS they found is not due to IBS.

 

[M Paine]

Thanks @Simon, I missed that in the study, and had not heard of I-FABP as a marker for intestinal permiability. That's fascinating and very thought provoking.

According to this paper, Intestinal fatty acid-binding protein (I-FABP) as a new biomarker for intestinal diseases:

intestinal fatty acid-binding protein(I-FABP) is specifically and abundantly present in epithelial cells of the mucosal layer of the small intestinal tissue

I-FABP is also considered to be rapidly released into the circulation just after small intestinal mucosal tissue is injured

I found the first quote confusing, abundantly present in epithelial cells of the mucosal layer. Are they saying it's part of epithelial cells? Or a part of the mucosa? Anyknow know?

Is it possible that I-FABP requires lysis of epithelial cells? Would tight-junction failure release I-FABP?

 

[Simon]

I found the first quote confusing, abundantly present in epithelial cells of the mucosal layer. Are they saying it's part of epitherlial cells? Or a part of the mucosa? Anyknow know?

Is it possible that I-FABP requires lysis of epithelial cells? Would tight-junction failure release I-FABP?

intestinal fatty acid-binding protein(I-FABP) is specifically and abundantly present in epithelial cells of the mucosal layer of the small intestinal tissue. I-FABP is also considered to be rapidly released into the circulation just after small intestinal mucosal tissue is injured

I-FAB is an abundant small protein within small intestine epithelial cells (enterocytes) needed for transporting and metabolising fatty acids. As it's within epithelial cells, it would need lysis of the cell to be released (as opposed to failure of tight junctions that hold the cells together).

we determined that the reference value of serum I-FABP concentration is designated to 2.0 ng/mL [=2,000 pg/l] or less in the circulation of normal healthy individuals.

The mean for patients was 234 pg/l and even the highest value for patients of 1,000 pg/l was within this normal range. So no sign at all of permeability, at least not by this measure. I don't think tight junction failure would release I-FAB, though it might lead to damage to epithelial cells as a secondary consequence.

 

[Bob]

There's a good article published in the Washington Post today. It's light on the science but a good article for general readers.

New study shows chronic fatigue isn’t just in your head. It may have to do with your gut.
By Ariana Eunjung Cha
June 30, 2016.
https://www.washingtonpost.com/news...in-your-head-it-may-have-to-do-with-your-gut/


Edited to add: the article now has a new title...

New study shows chronic fatigue syndrome may have to do with gut microbes
By Ariana Eunjung Cha
June 30, 2016.

.

 

[Comet]

There's a good article published in the Washington Post today. It's light on the science but a good article for general readers.

New study shows chronic fatigue isn’t just in your head. It may have to do with your gut.
By Ariana Eunjung Cha
June 30, 2016.
https://www.washingtonpost.com/news...in-your-head-it-may-have-to-do-with-your-gut/

Great article!
It got the "ridiculous concept" quote in from Maureen Hanson too:

...said Maureen Hanson, a professor of molecular biology and genetics at Cornell. “Furthermore, our detection of a biological abnormality provides further evidence against the ridiculous concept that the disease is psychological in origin.”

Another great quote, from @viggster:

In an open letter to the National Institutes of Health's director, Francis Collins, last year, my former colleague Brian Vastag described the devastating toll that the condition has taken on his own life and decried the lack of progress in research:

In the past, you've shown a soft spot for certain orphan diseases. Well, the history of ME is akin to having locked an entire orphanage in a cellar and bulldozing the house.

 

[viggster]

I asked Ariana to change the headline to "chronic fatigue syndrome"...