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Gut Bacteria Are Different in People With Chronic Fatigue Syndrome (TNYT)

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
"The scientists also discovered that people with C.F.S. had higher blood levels of lipopolysaccharides, inflammatory molecules that may indicate that bacteria have moved from the gut into the bloodstream, where they can produce various symptoms of disease."

are lipopolysaccharides in the bloodstream proof of leaky gut?

Elevated LPS from bacteria you'd expect to see in the gut would be. I think they're just not calling it 'leaky gut' because the alt. medicine practitioners pioneered the idea of inflammation causing leaky gut and leading to food intolerances (the latter of which is still 'imaginary' in the minds of many mainstream practitioners). Now there is better evidence that this is a common phenomena, but mainstream med has to call it something else, or it will keep the alt med connection in people's minds. It's a 're-branding' of an old idea.

Also, the researchers had other markers that specifically indicated gut damage, apart from LPS.

What are 'firmicutes'? Are they the Beneficial Bacteria in the gut?

Firmicutes is a huge and inspecific category that contains many kinds of bacteria, some of which are associated with illness, some of which are associated with good health.

My Genova test did not mention firmicutes.

Perhaps they broke things down more or less specifically. Clostridium, e.g. are Firmucutes -- bet they mentioned those.

I had RedLabs stool test done last year. My bacterial findings were identical to those in the study -- even the inflammatory markers followed the patterns they talk about. The only difference is that my level of bacterial diversity was exactly mid-range normal. I had almost never in my life taken antibiotics at that time. After long-term abx, I wonder what the story would be, now.

My article on this study and other gut studies is up on #MEAction as of yesterday -- it has more info than I've put here. :) Follow the link on the title below

New research: gut microbes identify 83% of patients

Gut-enterotype-e1468376165912-330x330.jpg

July 13, 2016

 
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ebethc

Senior Member
Messages
1,901
Elevated LPS from bacteria you'd expect to see in the gut would be. I think they're just not calling it 'leaky gut' because the alt. medicine practitioners pioneered the idea of inflammation causing leaky gut and leading to food intolerances (the latter of which is still 'imaginary' in the minds of many mainstream practitioners). Now there is better evidence that this is a common phenomena, but mainstream med has to call it something else, or it will keep the alt med connection in people's minds. It's a 're-branding' of an old idea.

Also, the researchers had other markers that specifically indicated gut damage, apart from LPS.

politics aside, is lps in the bloodstream evidence of leaky gut (or "intestinal permeability"...)? I think you're saying "yes" ... so, is there a blood test for this?

thanks.
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
For the 83% accuracy is there a breakdown for false positives and false negatives?

They do:

40168_2016_171_Fig6_HTML.gif

Fig 6
Receiver operating characteristic curves (a) for controls and ME/CFS patients determined using the inflammatory markers and sequencing datasets (even sampled at 32,233 sequences) and a supervised learning approach with randomForest algorithm and (b) confusion matrix for random forest analysis (values are presented as percentage) and ROC area under the curve (AUC) value for 97 % OTUs collapsed at the genus level. Mean AUC ROC value for five times repeated, 10-fold cross validation

The bottom graph is an error matrix (or a 'confusion matrix'). The upper left-hand shows percentage that did NOT have markers that were supposed to NOT have markers. The bottom right hand corner shows the percentage that WERE supposed to have markers who DID have markers.

Below is a simplified example in order to demonstrate how the above type of chart works:

confusion_matrix_simple2.png


Basically, the 30.09% were 'right' and the 52.93% was also 'right', giving us an 83% correct total percentage likelihood of identifying controls and ME patients correctly.

At least, that is what I can tell with my common sense -- I would never claim to be a stats expert!!!

The full-text is available. They also have an additional data file attached to the article that further describes this data. (How refreshing, eh?)
 
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JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
politics aside, is lps in the bloodstream evidence of leaky gut (or "intestinal permeability"...)? I think you're saying "yes" ... so, is there a blood test for this?

thanks.

That's def the way they're making it sound in the article, for sure. Being pedantic, LPS elevated in blood just means a gram-positive bacterial infection that has made it to the general bloodstream -- from anywhere.

From the article on #MEAction:

ME/CFS patients showed significantly higher levels of lipopolysaccharides (LPS) in their blood, which means that they had more gram-negative bacteria than controls. These elevated levels of bacteria then caused the liver to produce LPS-binding protein, which was also elevated above levels found in controls. sCD14 is one of the ways that the body senses invading bacteria. Levels of this inflammatory marker are high in those experiencing severe bacterial infections. CD14 levels were also high in ME/CFS patients.

I was careful not to say that the inflammatory markers on their own prove that the infection is in the gut. However, the LPS plus the markers for gut damage plus the dysbiosis is probably enough to reasonably claim that LPS are elevated because of infections in the gut.

sCD-14 is a reasonable blood test for systemic infection IMO. They used it in this study, and I've had it tested, so I know it's commercially available.

FWIW, mine was high!

-J
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
I really would've liked to have seen this for patients that met ICC rather than Fukuda. I'll bet it would have been easier to predict who was who, since the CCC and ICC criteria are more specific, and likely contain a narrower range of illness-types than Fukuda's CFS.
 

rosie26

Senior Member
Messages
2,446
Location
NZ
I'm going to play devil's advocate here and say our diet on average differs from regular people. When we lack energy our diets tend to be more spartan and less varied. And I know for my IBS I have to avoid a lot of foods. Given the expected reduced food diversity intake of PWME and IBS shouldn't it be expected that there is less species in our stool?

Has the above type of argument been ruled out?
I've never been a 'takeaways' kind of person. I've always cooked a fair variety of food and have been fortunate enough not to have problems. There are just a small amount of foods that I have to be careful not to eat too many days in a row and one of those is tomato's.

I think looking back, I wish I had taken a multivitamin at least once a week along with a B complex for the last 20 years. I do think now, that this illness robs us/me of more minerals than should be. I could be wrong but I could never understand why I had so many problems with my teeth and my bone density was not as good as it should have been in my thirties.
 
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JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
A new book on the microbiome's relationship to chronic illness is coming out this October! I added it to the bottom of the article, with a link. It has a whole chapter on gut dysbiosis and the CNS! :wide-eyed: :D :thumbsup:
 

kangaSue

Senior Member
Messages
1,857
Location
Brisbane, Australia
politics aside, is lps in the bloodstream evidence of leaky gut (or "intestinal permeability"...)? I think you're saying "yes" ... so, is there a blood test for this?

thanks.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980675/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980675/
[Translocation of bacteria and their products
Breakdown of the mucosal barrier potentially leads to translocation of microbiota or their toxic products. Two promising plasma markers, reflecting translocation of bacteria or their products, are D-lactate and endotoxin lipopolysaccharide (LPS), which are metabolic products or components of the commensal bacteria of the gastrointestinal tract. D-lactate is only produced by bacteria as a product of bacterial fermentation[10]. Baseline levels of D-lactate in healthy subjects are very low. Increased levels of D-lactate have been correlated with conditions in which the number of bacteria elevates rapidly, including in patients with bacterial overgrowth due to infection, short bowel syndrome, and mesenteric ischaemia[11]. LPS, the major constituent of the outer membrane of Gram-negative bacteria, is released by Gram-negative bacteria when replicating or dying. Increased circulating LPS levels have been related to an impaired mucosal barrier. The presence of LPS can be measured directly in blood, e.g. by the Limulus Amoebocyte Lysate assay[12]. In addition, anti-LPS antibodies can be measured by endotoxin-core antibody (EndoCAb), an indirect measurement of LPS leakage into the circulation[13]. A drop in levels of circulating anti-LPS antibodies is considered to indicate consumption of antibodies to LPS by exposure to LPS[14].]
 

kangaSue

Senior Member
Messages
1,857
Location
Brisbane, Australia
As bacterial translocation is implied to occur in concert with the breakdown of the mucosal barrier in a host of conditions that result in GI dysfunction, something to keep an eye out for is delayed release phophatidylcholine which has been shown to heal the mucosal barrier in trials into Ulcerative Colitis.
http://www.nature.com/ajg/journal/v109/n7/full/ajg2014104a.html

There is another product already on the market out of Germany that is available in some European countries, PC Medicus Phosphatidylcholine. It's not the same strength as that being used in the UC trials but it's available on the amazon.uk website
 

TiredSam

The wise nematode hibernates
Messages
2,677
Location
Germany
They do:

40168_2016_171_Fig6_HTML.gif

Fig 6
Receiver operating characteristic curves (a) for controls and ME/CFS patients determined using the inflammatory markers and sequencing datasets (even sampled at 32,233 sequences) and a supervised learning approach with randomForest algorithm and (b) confusion matrix for random forest analysis (values are presented as percentage) and ROC area under the curve (AUC) value for 97 % OTUs collapsed at the genus level. Mean AUC ROC value for five times repeated, 10-fold cross validation

The bottom graph is an error matrix (or a 'confusion matrix'). The upper left-hand shows percentage that did NOT have markers that were supposed to NOT have markers. The bottom right hand corner shows the percentage that WERE supposed to have markers who DID have markers:

confusion_matrix_simple2.png


Basically, the 30.09% were 'right' and the 52.93% was also 'right', giving us an 83% correct total percentage likelihood of identifying controls and ME patients correctly.

At least, that is what I can tell with my common sense -- I would never claim to be a stats expert!!!

The full-text is available. They also have an additional data file attached to the article that further describes this data. (How refreshing, eh?)

Sorry I'm getting confused by this. I thought that table b referred to percentages of participants, but it can't because when you convert the percentage figures back to actual number of participants, 5.11 percent of 87 participants (48 ill + 39 controls) is 4.4457 actual participants instead of a whole number.

Also the table below doesn't show percentages (or they would add up to 100), and if it shows actual participants, why has the number gone up from 87 to 165, and why have the proportions changed from table b?
 

mermaid

Senior Member
Messages
714
Location
UK
Firmicutes is a huge and inspecific category that contains many kinds of bacteria, some of which are associated with illness, some of which are associated with good health.

Perhaps they broke things down more or less specifically. Clostridium, e.g. are Firmucutes -- bet they mentioned those.

I had RedLabs stool test done last year. My bacterial findings were identical to those in the study -- even the inflammatory markers followed the patterns they talk about. The only difference is that my level of bacterial diversity was exactly mid-range normal. I had almost never in my life taken antibiotics at that time. After long-term abx, I wonder what the story would be, now.

My article on this study and other gut studies is up on #MEAction as of yesterday -- it has more info than I've put here. :) Follow the link on the title below

New research: gut microbes identify 83% of patients

Gut-enterotype-e1468376165912-330x330.jpg

July 13, 2016

@JaimeS Thank you. Actually Clostridium didn't get a mention, but there is Lactobacillus species - no growth, and E Coli (lots), and Bifidobacterium (not much). Also some additional bacteria listed - gamma and alpha haemotylic Streptococcus (lots), and also lots of Pseudomonas species, and a little Bacillus species. That was it on that area of the test though of course there were other issues.
Perhaps your Redlabs test was more wide ranging than the Genova one.

What are the inflammatory markers I should be looking for please? I did see a private Dr a few years after the test who advised me re various supplments based on the test, including Digestive Enzymes which I now take as some of my markers were off though not too drastically. I also now see a medical herbalist regularly.

Thank you for the link re the article... I will take a look....
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
@JaimeS Thank you. Actually Clostridium didn't get a mention, but there is Lactobacillus species - no growth, and E Coli (lots), and Bifidobacterium (not much). Also some additional bacteria listed - gamma and alpha haemotylic Streptococcus (lots), and also lots of Pseudomonas species, and a little Bacillus species. That was it on that area of the test though of course there were other issues.
Perhaps your Redlabs test was more wide ranging than the Genova one.

What are the inflammatory markers I should be looking for please? I did see a private Dr a few years after the test who advised me re various supplments based on the test, including Digestive Enzymes which I now take as some of my markers were off though not too drastically. I also now see a medical herbalist regularly.

Thank you for the link re the article... I will take a look....

If you check out the article, I list the inflammatory markers quite early. :)

-J
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Sorry I'm getting confused by this. I thought that table b referred to percentages of participants, but it can't because when you convert the percentage figures back to actual number of participants, 5.11 percent of 87 participants (48 ill + 39 controls) is 4.4457 actual participants instead of a whole number.

Also the table below doesn't show percentages (or they would add up to 100), and if it shows actual participants, why has the number gone up from 87 to 165, and why have the proportions changed from table b?

I'm not quite sure what you're saying, but if you're comparing table b to the table after it, I just included the table after it to show what that sort of table is meant to show. The last one was just an example to demonstrate that type of table more clearly. :)
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Looking at the statistics you provided I'm going to say it probably wouldn't matter.

Looking at the n=165 table: Controls were predicted correctly 83.3% of the time. CFS was predicted correctly 95% of the time. If people from the CFS group didn't have CFS we would expect the CFS group prediction rate to be shifted lower. So a MAXIMUM of 5% of the CFS group COULD be misidentified with CFS.

For the other derived table that has the final 83% prediction rate I think they are averaging over the entire population (~99% controls, ~1% CFS). That would explain why it matches the control group rate. It's also possible that it is due to posthoc analysis but I would have read it to figure that out :p

It's really promising though that for patients fulfilling the CFS criteria they have a 95% prediction rate :hug:

Not quite sure I totally understand. I think I'm fried for today! :D

-J
 

msf

Senior Member
Messages
3,650
"I knew two ppl with CFS and they were both depressed."

I love the logic (or lack of it) of this comment. Let´s see, if someone knew two people with CFS and both were depressed that could have at least four implications: one, which I believe the poster was driving at, is that CFS is just depression; two, the people did not actually have CFS (which is something other than depression) and actually had depression; three, the poster (who was probably not a psychiatrist) wrongly diagnosed them with depression; four, they had both CFS and depression.

Now, we are to prefer explanation one because...

This is why only smart people should be doctors.
 

TiredSam

The wise nematode hibernates
Messages
2,677
Location
Germany
I'm not quite sure what you're saying, but if you're comparing table b to the table after it, I just included the table after it to show what that sort of table is meant to show. The last one was just an example to demonstrate that type of table more clearly. :)
I'm just trying to find out how many of the 48 ill participants were correctly identified as having CFS, and how many of the 39 controls were correctly identified as not having CFS. I've looked at the paper and the table in this thread but I still can't manage to extract that information. Converting the percentages in the table back to number of participants doesn't seem to work without ending up with half a participant, so I was wondering why.