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Fecal metagenomic profiles in subgroups of patients with ME/CFS

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
I'm curious, does Lipkin write about SIBO in this or another study?

I"m not aware of Lipkin writing about SIBO specifically, just an altered microbiome.


to what degree is the small intestine in CFS/ME deranged as opposed to standalone SIBO? I guess I would like to see study like this comparing CFS/ME+SIBO to CFS/ME and SIBO instead of IBS.

I would like to see a study like that also! From all the reading I have done, there are varying degrees of SIBO. Some people can have SIBO and not have any significant degree of leaky gut.

Others can have SIBO and a leaky gut that ranges from mild to severe, with various degrees of bacterial translocation (ie.-LPS). There are of course many factors, that you are probably aware of, that make one more or less vulnerable to the severity of SIBO and a leaky gut.

Many of the triggers of CFS are also known to cause or worsen, SIBO/dysbiosis and a leaky gut. Excessive stress from everyday life, a viral or bacterial infection, a car accident or the loss of a loved one,etc. can have a big impact on the microbiome and a leaky gut.

These triggers might, in some cases, be the straw that broke the camels back, so to speak. Here is paper talking about stress and an altered microbiome.

The composition of the core bacteria that we harbour throughout our adult life is established early in our first few years of life and are shaped by a number of factors including mode of delivery (vaginal or C-section), whether we are breastfed or bottlefed, diet, medication (in particular antibiotic medication), and exposure to viral or bacterial infections and stress (Borre et al., 2014b).

Chronic stress also can cause or worsen a leaky gut -

Chronic stress also makes the gut leaky, increasing circulating levels of LPS.
LINK

ETA: Thanks for the hesperidin and lps link- I will definitely read!
 
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Manganus

Senior Member
Messages
166
Location
Canary islands
That is quite different from what I was talking about which is bacterial translocation - when gut bugs end up in the blood stream. There is really only one way for them to get there - through the intestinal wall/tight junctions. They should definitely NOT be in the blood stream - can lead to sepsis and death and every effort should be made to treat them with antimicrobials, and then attempt to tighten up the junctions in the gut that are letting them through. I wasn't suggesting treating an altered microbiome WITHOUT translocation with nuke level abx.

Sorry to have to ask, but in my understanding it's a huge difference between, on one hand, free LPS that may be dissolved in the intestinal fluids and get squeezed through thin gaps of the intestinal wall, when too many tight junctions have given up, resulting in a gap between the epithelial cells, and on the other hand whole bacteria, that ends up outside of the intestin, in the tissues, gets into the lympatic system, and possibly into the blood stream.

Without doing the math, I think the dimensions of the gap that bacterias can pass through must be magnitudes larger that that kind of gaps that LPS may get filtered through.



200px-LPS.svg.png
 

aaron_c

Senior Member
Messages
691
When trying to kill off specific bacteria the only strategy I am aware of is to kill them all and repopulate. Is anyone aware of other scientifically established protocols?

I'd be very careful about just trying to strike off different bacteria without any testing or help from a specialized doctor. I had a bacteroides overgrowth(40%) and now I am left with a streptococcus overgrowth. Both take different meds to cure apparently.

My concern is mostly that prior to a fecal transplant I am supposed to take antibiotics--but I'm not clear on what antibiotics I should take. Like Solstice, I am under the impression that some antibiotics are better at killing some bugs than others. So this gives me an idea of what bugs I should make sure that my antibiotic can kill.

Maybe it's not that simple? But that was my thinking.
 

aaron_c

Senior Member
Messages
691
@AdamS that is very interesting! I see that alcoholic and lactic acid fermentation. The only thing that relieve my ME is alcohol. Lots of alcohol. 12 beers makes me feel almost 100% healthy. Could this have anything to do with that?

I have this too. I'm a bit of a lightweight with alcohol, although I don't know if that's ME/CFS or just how little I drink. But I get more energy from just a glass or possibly two of wine (that's as much as I ever drink). Even after the "drunk" wears off, for the next 24 hours my energy is way better!

I've always figured that this "cure" would have diminishing returns, so I haven't really done much with it. It would be interesting if there were some kind of connection to the metabolics of my gut bacteria.
 

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Just wait for someone to test LPS and cytokine levels in people with ME after exercise. I believe we will see a much stronger correlation, with a greater separation between cases and controls.


This study is not exactly what you are looking for, but it might be something you want to look at, if you haven't already.
LINK

We speculate that these bacteria may have translocated into the blood stream from the gut after the maximal exercise challenge.
 

Cheesus

Senior Member
Messages
1,292
Location
UK
They should definitely NOT be in the blood stream - can lead to sepsis and death and every effort should be made to treat them with antimicrobials, and then attempt to tighten up the junctions in the gut that are letting them through.

@Manganus

It is actually quite normal to have bacterial translocation from the gut into the bloodstream. If you run shotgun metagenomics on the blood of a healthy person, you will find a diverse array of microbial DNA.

BACKGROUND:
Recent studies have revealed that the blood of healthy humans is not as sterile as previously supposed. The objective of this study was to provide a comprehensive description of the microbiome present in different fractions of the blood of healthy individuals.

STUDY DESIGN AND METHODS:
The study was conducted in 30 healthy blood donors to the French national blood collection center (Établissement Français du Sang). We have set up a 16S rDNA quantitative polymerase chain reaction assay as well as a 16S targeted metagenomics sequencing pipeline specifically designed to analyze the blood microbiome, which we have used on whole blood as well as on different blood fractions (buffy coat [BC], red blood cells [RBCs], and plasma).

RESULTS:
Most of the blood bacterial DNA is located in the BC (93.74%), and RBCs contain more bacterial DNA (6.23%) than the plasma (0.03%). The distribution of 16S DNA is different for each fraction and spreads over a relatively broad range among donors. At the phylum level, blood fractions contain bacterial DNA mostly from the Proteobacteria phylum (more than 80%) but also from Actinobacteria, Firmicutes, and Bacteroidetes. At deeper taxonomic levels, there are striking differences between the bacterial profiles of the different blood fractions.

CONCLUSION:
We demonstrate that a diversified microbiome exists in healthy blood. This microbiome has most likely an important physiologic role and could be implicated in certain transfusion-transmitted bacterial infections. In this regard, the amount of 16S bacterial DNA or the microbiome profile could be monitored to improve the safety of the blood supply.

https://www.ncbi.nlm.nih.gov/pubmed/26865079
 
Messages
516
So... I truly appreciate they did this study (especially from still having IBS-D), but I can't find anything very actionable, to be expected. The gut is out of my league and my only working solutions involve drastic avoidance.

Is there anyone who's researched the gut populations enough to have any practical ideas based on the distributions, like aaron posted? There was a member @Vegas who seemed to know what he was doing, but he hasn't posted lately... I'd like to know what he thinks...
 

Murph

:)
Messages
1,799
Just wanted to shout out to @ljimbo423 for the link above. That's a good paper that I'd forgotten, and very relevant here.

Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005).

There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls.

These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls.

In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.

This chart shows certain bacteria in the blood at baseline and 15 minutes post exercise.
Screen Shot 2017-04-28 at 7.13.29 AM.png

--

Also, as far as thinking about why changed gut bacteria might be relevant, we should keep in mind the vagus nerve as well as the gut wall.

I was briefly involved in a Twitter exchange with Michael van Elzakker, Harvard Postdoc and ME/CFS researcher. He says "Vagus nerve samples the enteric microbiota on an ongoing basis; probably some peoples' ME/CFS symptoms are driven by inflammatory gut flora."

The vagus nerve links the gut and the brain (which is itself an immune mediation centre) and could in theory cause the brain to trigger systemic effects.
 
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Also, as far as thinking about why changed gut bacteria might be relevant, we should keep in mind the vagus nerve as well as the gut wall.

I was briefly involved in a Twitter exchange with Michael van Elzakker, Harvard Postdoc and ME/CFS researcher. He says "Vagus nerve samples the enteric microbiota on an ongoing basis; probably some peoples' ME/CFS symptoms are driven by inflammatory gut flora."

The vagus nerve links the gut and the brain (which is itself an immune mediation centre) and could in theory cause the brain to trigger systemic effects.
You might find this article (http://neurosciencenews.com/parkinsons-vagotomy-6518/) based on this paper (http://www.neurology.org/content/early/2017/04/26/WNL.0000000000003961.short) interesting then.
Parkinson’s disease may start in the gut and spread to the brain via the vagus nerve, according to a study published in the April 26, 2017, online issue of Neurology. The vagus nerve extends from the brainstem to the abdomen and controls unconscious body processes like heart rate and food digestion.

The preliminary study examined people who had resection surgery, removing the main trunk or branches of the vagus nerve. The surgery, called vagotomy, is used for people with ulcers. Researchers used national registers in Sweden to compare 9,430 people who had a vagotomy over a 40-year period to 377,200 people from the general population. During that time, 101 people who had a vagotomy developed Parkinson’s disease, or 1.07 percent, compared to 4,829 people in the control group, or 1.28 percent. This difference was not significant.

But when researchers analyzed the results for the two different types of vagotomy surgery, they found that people who had a truncal vagotomy at least five years earlier were less likely to develop Parkinson’s disease than those who had not had the surgery and had been followed for at least five years. In a truncal vagotomy, the nerve trunk is fully resected. In a selective vagotomy, only some branches of the nerve are resected.
 

msf

Senior Member
Messages
3,650
I know how severe it is.

Joke? Or are you avoiding the obvious implication of the sentence I quoted from the paper, which was that they are interested in the gut in ME because it might be a way of controlling the severity of the illness?
 

M Paine

Senior Member
Messages
341
Location
Auckland, New Zealand
Yes I'm aware of that. The point I was making was that the long duration cases do rather contradict a hypothesis based on bacterial translocation causing systemic inflammation as an ongoing driver of ME/CFS symptoms.

Rather than just 'different' systemic inflammation should be easily recognisable. That's not to say that an inflammatory process at the early stages might not be able to establish a stable self-perpetuating (neuro)immune disease state in the absence of ongoing peripheral stimulation - but that's a different hypothesis.

Compared to controls typical markers for inflammation are often elevated in ME/CFS patients (CRP, IL-6, neopterin etc..). It's not that these patient groups don't have elevated markers for inflammation, rather that they cannot identify a consistent pattern.
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
To me it seems like changes in the microbiome could be a consequence rather than a cause of ME. I'm definitely interested to hear logical arguments as to why I could be wrong though! :)

Or right....

This 2-minute video is worth a watch: describes a triggering infection, think of the ME/CFS "hit-and-run" theory, which then causes microbiota dysfunction and translocation leading to chronic disease (animal model); research published in Cell with commentary in Science:


@Simon wrote an excellent post in 2015 about the findings:

http://forums.phoenixrising.me/inde...t-infection-in-mouse-study.40408/#post-650239
 

Seven7

Seven
Messages
3,444
Location
USA
Wound't we see more Chron's Desease here?? I do have colitis which is related, since the low bacteria Faecalibacterium is implicated in several other diseases.
 

cigana

Senior Member
Messages
1,095
Location
UK
This study is not exactly what you are looking for, but it might be something you want to look at, if you haven't already.
LINK
Very interesting and relevant, thanks.

A general question: how can LPS in plasma make you feel ill if there is no cytokine/C4a/CD14 response?
(My understanding was that the immune response to LPS was what made you ill - is this not true?)
 

cigana

Senior Member
Messages
1,095
Location
UK
Also, as far as thinking about why changed gut bacteria might be relevant, we should keep in mind the vagus nerve as well as the gut wall.

I was briefly involved in a Twitter exchange with Michael van Elzakker, Harvard Postdoc and ME/CFS researcher. He says "Vagus nerve samples the enteric microbiota on an ongoing basis; probably some peoples' ME/CFS symptoms are driven by inflammatory gut flora."

The vagus nerve links the gut and the brain (which is itself an immune mediation centre) and could in theory cause the brain to trigger systemic effects.
I'm suddenly much more interested in the vagus nerve hypothesis now!
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Joke? Or are you avoiding the obvious implication of the sentence I quoted from the paper, which was that they are interested in the gut in ME because it might be a way of controlling the severity of the illness?

If they had set out plausible hypothesis supporting this I'd welcome it. I just don't see it in this paper.