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

[Forbin]

This may be a naive question, but... in Crohn's, ulcerative colitis, dysentery and even in stomach ulcers you can have blood getting into the GI tract. If blood can get in, can "microbial components" take the same route out?

 

[kangaSue]

This may be a naive question, but... in Crohn's, ulcerative colitis, dysentery and even in stomach ulcers you can have blood getting into the GI tract. If blood can get in, can "microbial components" take the same route out?

Don't know about the blood side of things but in Crohn's and UC, translocation of bacteria is also possible through breakdown of the mucosal layer. Microvascular Ischemia (a form of Chronic Mesenteric Ischemia) is something being looked at as a causative for IBD's and is the form of bowel ischemia I have which causes me gastroparesis and chronically impaired GI function including major food and medication intolerance.
http://www.ncbi.nlm.nih.gov/pubmed/19685450
http://onlinelibrary.wiley.com/doi/10.1196/annals.1326.003/abstract

 

[M Paine]

This may be a naive question, but... in Crohn's, ulcerative colitis, dysentery and even in stomach ulcers you can have blood getting into the GI tract. If blood can get in, can "microbial components" take the same route out?

I don't think this is naive, it sounds like a very good question. As far as I know, the jury is still out on if bacterial, or just their cellular components are getting out of the gut, and into the bloodstream. Measuring for antibodies against LPS just tells you that the outer membrane is in the blood. Doing PCR would tell you that Nucleic Acid is in the blood.

Perhaps the size of the gaps in the tight junctions does not permit molecules of any great size to pass through. Red blood cells are fairly large in the scheme of things. Most bacteria are many times smaller.

 

[EastTenn]

I'm convinced my CFS arose because I was on tetracycline for more than a year as an anti-acne regiment when I was a teenager in the 70's. The antibiotics killed off much of my beneficial bacteria and a massive fungal overgrowth messed up my small intestinal lining. I was rarely ill before, but often got viral symptons after. Didn't know anything about probiotics then.

 

[Biarritz13]

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].

Is high value of lactate during exercice due to this translocation of microbiota or is it due to an issue with some metabolites?

 

[kangaSue]

Is high value of lactate during exercice due to this translocation of microbiota or is it due to an issue with some metabolites?

I'm not qualified to give an informed answer on that, just be aware that measurement of lactate levels from exercise usually looks at L-lactate which is a normal product of anaerobic metabolism but D-lactate is a reflection of bacterial overgrowth in the gastro-intestinal tract that's usually encountered in short bowel syndrome.
http://www.biolab.co.uk/docs/dlactate.pdf

 

[JaimeS]

Anyone want to show their results? My metagenomics stool analysis (through Red Labs):

Fimicutes were 49%, normal would be 50-85% in Europeans. The test indicated that I have low diversity. My sCD1 was also high, but just barely. Seems loosely in line with the findings here.

The "Firmicutes being off" thing has been found in three studies so far:

Post-exertionally, Shukla et al. (2015) found that both blood and stool sample microbiota differed significantly in ME/CFS patients in the abundance of “several major bacterial phyla”, especially Bacilli in blood 48 hours post-exercise and Clostridium XIVa and IV (Firmicutes) in blood samples collected 15 minutes after exercise. Following exercise challenge,

“there was an increase in relative abundance of 6 of the major 9 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... in ME/CFS patients versus... controls” (Shukla et al., 2015).

Though this was a very small study, other studies have verified dysregulation in the intestinal microbiota in ME, CFS, or ME/CFS as defined by the CCC. Moreover, these findings were consistent with those in the previous study, featuring a significant dysregulation in the Firmicutes phylum in Norwegian ME patients over controls, including a fifty-fold decrease in Holdmemania, a 20-fold increase in Lactonifactor, and Bacteriodes genera Alistipes (Frémont, Coomans, Massart, & De Meirlier, 2013).

Recently, Giloteaux et al. (2016) measured plasma levels of hsCRP, lipopolysaccharides (LPS) as a marker for microbial translocation, and intestinal fatty acid binding protein (I-FABP) as a marker for GI damage. ME/CFS patients showed significantly higher LPS, sCD14, and plasma LBP.

“ME/CFS samples had a significant overall lower microbial diversity.... [which] differed at the phylum and family levels...” which were so distinctive that utilizing a machine learning approach, differences in bacterial populations could be used to accurately diagnose 82.93% of ME/CFS patients (Giloteaux et al., 2016). Giloteaux et al. also found dysregulation in Firmicutes gut populations in particular.

Ref:
Frémont, M., Coomans, D., Massart, S., & De Meirlier, K. (2013, August). High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients. Anaerobe, 22, 50-56. doi:10.1016/j.anaerobe.2013.06.002

Giloteaux, L., Goodrich, J. K., Walters, W. A., Levine, S. M., Ley, R. E., & Hansen, M. R. (2016, June 23). Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome, 4(30), 1-12. http://doi.org/10.1186/s40168-016-0171-4

Shukla, S. K., Cook, D., Meyer, J., Vernon, S. D., Le, T., Clevidence, D., … Frank, D. N. (2015). Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PLoS ONE, 10(12), e0145453. http://doi.org/10.1371/journal.pone.0145453

 

[JaimeS]

Mine were 'off' in Redlabs as well.

 

[John Mac]

The study has now been covered in a New York Times blog by Nicholas Bakalar

http://well.blogs.nytimes.com/2016/...rent-in-people-with-chronic-fatigue-syndrome/

 

[Horizon]

I'm really pleased the media is covering this because they can use the sensational headline that CFS is not in your head, it's in your gut!

I wish there was more clarity on what specific organisms are missing or low. Are any of these ones we can buy as a probiotic supplement?

 

[CaptainA]

I wish there was more clarity on what specific organisms are missing or low. Are any of these ones we can buy as a probiotic supplement?

I second this question? I've heard antidotal accounts of people hap hazardly shoving every different probiotic strain possible into their bodies and getting better which I think could possibly turn out bad for some people. I also know that some of these bacteria can't be grown in a lab. I would love to see which ones are missing and the best way to get them back apart from finding those Amazonian tribespeople with no contact with the outside world and amazing gut flora do to a fecal transplant with.

 

[knackers323]

I missed what condition it was for but going by the rest of the bulletin and the info here I think this was reported on aust syd radio today. 101.7 2pm news broadcast

 

[Forbin]

I wish there was more clarity on what specific organisms are missing or low. Are any of these ones we can buy as a probiotic supplement?

Dr. Hanson addresses this question near the end of this radio interview on WRFI community radio in New York.

http://www.wrfi.org/2016/06/28/dr-m...bout-chronic-fatigue-syndrome-june-28th-2016/

INTERVIEWER: And the bacteria that are missing from the microbiomes of CFS patients... Can they be restored by taking probiotics, or eating yogurt, or eating fermented vegetables that have various bacteria?

DR. HANSON: No... when we say there is reduced diversity, these are not the common bacteria that you could get by eating yogurt or taking probiotics. Whether taking probiotics might help in other ways, we don't really know. We'd need to do a controlled trial to find that out. But, no, the bacteria that are missing are not ones that you can easily just take by ingesting some sort of food.

 

[kangaSue]

DR. HANSON: No... when we say there is reduced diversity, these are not the common bacteria that you could get by eating yogurt or taking probiotics. Whether taking probiotics might help in other ways, we don't really know. We'd need to do a controlled trial to find that out. But, no, the bacteria that are missing are not ones that you can easily just take by ingesting some sort of food.

If the implication here is that the reduced species is anaerobic, maybe openbiome's FMT product could be an answer seeing as they use an anaerobic extraction process.
http://www.openbiome.org/treatment-information/

 

[Forbin]

If the implication here is that the reduced species is anaerobic, maybe openbiome's FMT product could be an answer seeing as they use an anaerobic extraction process.
http://www.openbiome.org/treatment-information/

Yes, I noticed that she did not include a reference to some form of fecal transplant in her answer. She did follow up by addressing the origin of the low diversity.

INTERVIEWER: Is it known why they [the bacteria] might by missing? Do the immune systems of affected patients attack those bacteria and eliminate them?

DR. HANSON: Well, that's a very interesting question. It's really not understood why people with this reduced diversity - why they do have a reduced diversity. It certainly is possible that the immune system is attacking those bacteria improperly, but it is also possible that the environment in the gut is less hospitable for those bacteria. Perhaps they're [the bacteria] not getting the nutrients as easily as they would like because of some issue with digestion or other aspects of the intestine.

If this is the case, simply replacing the missing bacteria might not be enough. The system may be actively suppressing the diversity of the microbiome as opposed to some kind of "hit and run" scenario.

 

[knackers323]

this is great news but haven't we seen these or similar findings before?

I remember when I first got sick 20 years ago Newcastle uni in AU came out with big news that they had found some answers through fecal tests. I'm pretty sure that was the start of bioscreen, I got the test done but nothing came of it.

there was some new finding that was advertised as "for the first time finding biomarkers in cfs proving it wasn't all in the head" just like this is being reported in many places just a couple years ago and I haven't heard anything of that again either.

are drs going to start testing us for these markers as routine now? will these results be excepted by gov, social security etc?

as others have said, there are still many questions. why does fmt help some and not others?

I believe they find similar abnormalities in autism also. I have heard of big improvements in that with probiotics but haven't heard of any cures, not that I have looked very hard.

it seems there is more to the story.

either a side effect of the true cause or there is something that is continually distorting the biodome.

the other question is. why has it taken so long for such a seemingly simple idea to be looked into and study to be done?

this should have been done years ago

 

[msf]

Is high value of lactate during exercice due to this translocation of microbiota or is it due to an issue with some metabolites?

In my case, my reaction to certain foods suggests it is the former.

 

[Bob]

Figure 5 in the paper shows the differences between ME/CFS patients and healthy controls at the genus/genera level.

Image:
https://static-content.springer.com/image/art:10.1186/s40168-016-0171-4/MediaObjects/40168_2016_171_Fig5_HTML.gif

Full paper:
https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4#Sec2

 

[Bob]

I wish there was more clarity on what specific organisms are missing or low. Are any of these ones we can buy as a probiotic supplement?

I second this question? I've heard antidotal accounts of people hap hazardly shoving every different probiotic strain possible into their bodies and getting better which I think could possibly turn out bad for some people. I also know that some of these bacteria can't be grown in a lab. I would love to see which ones are missing and the best way to get them back apart from finding those Amazonian tribespeople with no contact with the outside world and amazing gut flora do to a fecal transplant with.

Dr. Hanson addresses this question near the end of this radio interview on WRFI community radio in New York.

http://www.wrfi.org/2016/06/28/dr-m...bout-chronic-fatigue-syndrome-june-28th-2016/

INTERVIEWER: And the bacteria that are missing from the microbiomes of CFS patients... Can they be restored by taking probiotics, or eating yogurt, or eating fermented vegetables that have various bacteria?

DR. HANSON: No... when we say there is reduced diversity, these are not the common bacteria that you could get by eating yogurt or taking probiotics. Whether taking probiotics might help in other ways, we don't really know. We'd need to do a controlled trial to find that out. But, no, the bacteria that are missing are not ones that you can easily just take by ingesting some sort of food.

I noticed that she did not include a reference to some form of fecal transplant in her answer. She did follow up by addressing the origin of the low diversity.

INTERVIEWER: Is it known why they [the bacteria] might by missing? Do the immune systems of affected patients attack those bacteria and eliminate them?

DR. HANSON: Well, that's a very interesting question. It's really not understood why people with this reduced diversity - why they do have a reduced diversity. It certainly is possible that the immune system is attacking those bacteria improperly, but it is also possible that the environment in the gut is less hospitable for those bacteria. Perhaps they're [the bacteria] not getting the nutrients as easily as they would like because of some issue with digestion or other aspects of the intestine.

If this is the case, simply replacing the missing bacteria might not be enough. The system may be actively suppressing the diversity of the microbiome as opposed to some kind of "hit and run" scenario.

I think it's worth keeping in mind that we know nothing about the reasons why there might be differences in gut flora. It could be one of, or a combination of, so many different reasons. And it might even be caused by an adaptive and protective response to the environment e.g. whereby the immune system is modifying the gut flora to reduce damage caused by a leaky gut. It might be potentially beneficial for ME/CFS patients to have an altered gut microbiome and it might be potentially harmful to replace the flora. Introducing new gut flora has the potential to overwhelm a weakened or dysfunctional immune system.

Some hypothetical reasons for differences...

• The immune system is dysfunctional (e.g. overactive or underactive), affecting gut flora balance.
• The immune system of ME/CFS patients mis-identifies and attacks certain gut bacteria as if they are harmful invading pathogens.
• A leaky gut might be playing havoc with the immune system; and, as a result, the immune system might be attacking certain gut bacteria either in a random response or in an adaptive response to reduce the damage caused by a leaky gut.
• Different concentrations of digestive fluids or bile causes changes in population.
• A different body temperature causes changes.
• An unusual population of bacteriophages causes differences in gut bacteria either by directly affecting the bacteria population or because they are recognised as pathogens by the immune system causing the immune system to go into overdrive.
• Unknown environmental factors may cause differences.
• Unidentified or identified gut infection/s (virus/bacteria/fungus) may be causing problems with the immune system.

These are just off the top of my heed. I'm sure there are zillions of other potential reasons.

 

[lansbergen]

I think it's worth keeping in mind that we know nothing about the reasons why there might be differences in gut flora. It could be one, or a combination of, so many different reasons. And it might even be caused by an adaptive and protective response to the environment whereby the immune system is modifying the gut flora in response to an infection. It might be potentially harmful to replace the flora. Introducing new gut flora has the potential to overwhelm a weakened or dysfunctional immune system.

Good thinking. Caution should be exercised