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Fecal metagenomic profiles in subgroups of patients with ME/CFS

Kati

Patient in training
Messages
5,497
This is a press release from eureka Alert regarding a new publication from the Lipkin team at Columbia University:

Chronic fatigue syndrome linked to imbalanced microbiome
Scientists identify abnormal levels of specific gut bacteria in individuals with chronic fatigue syndrome, including those with and without co-morbid IBS

https://eurekalert.org/pub_releases/2017-04/cums-cfs042117.php

Exerpt:

Scientists at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health have discovered abnormal levels of specific gut bacteria related to chronic fatigue syndrome/myalgic encephalomyelitis, or ME/CFS, in patients with and without concurrent irritable bowel syndrome, or IBS. Findings are published in the journal Microbiome.

The study is among the first to disentangle imbalances in the gut bacteria in individuals with ME/CFS and IBS. ME/CFS is a complex, debilitating disorder characterized by extreme fatigue after exertion and other symptoms including muscle and joint pain, cognitive dysfunction, sleep disturbance, and orthostatic intolerance. Up to 90 percent of ME/CFS patients also have IBS.

The researchers followed 50 patients and 50 matched healthy controls recruited at four ME/CFS clinical sites. They tested for bacterial species in fecal samples, and for immune molecules in blood samples.

They report:



  • Levels of distinct intestinal bacterial species--Faecalibacterium, Roseburia, Dorea, Coprococcus, Clostridium, Ruminococcus, Coprobacillus--were strongly associated with ME/CFS; their combined relative abundance appeared to be predictive of diagnosis




  • Increased abundance of unclassified Alistipes and decreased Faecalibacterium were the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS




  • An analysis of bacterial metabolic pathways associated with disturbances in gut bacteria revealed distinct differences between ME/CFS and ME/CFS subgroups relative to healthy controls




  • In ME/CFS subgroups, symptom severity measures, including pain and fatigue, correlated with the abundance of distinct bacterial types and metabolic pathways




  • No changes were observed in immune markers--a finding that may reflect the dearth of participants who had been ill for a short time; earlier research suggests immune changes may only be evident when comparing short and long duration cases


More at the link above. I do not have a link to the paper as of yet.

Edit: for the purpose of clarity, here is the full abstract and the link to open access paper:

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome
  • Dorottya Nagy-Szakal†, Brent L. Williams†, Nischay Mishra, Xiaoyu Che, Bohyun Lee, Lucinda Bateman, Nancy G. Klimas, Anthony L. Komaroff, Susan Levine, Jose G. Montoya, Daniel L. Peterson, Devi Ramanan, Komal Jain, Meredith L. Eddy, Mady Hornig and W. Ian Lipkin
†Contributed equally
Microbiome20175:44
DOI: 10.1186/s40168-017-0261-y

Received: 11 January 2017, Accepted: 4 April 2017, Published: 26 April 2017

Abstract

Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS).

The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear.

We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling.

Results

Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules.

IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways.

Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy.

Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS.

Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroidesabundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS.

Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity.

Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort.

In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways.

Conclusions

Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity.

However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS.

These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.

Keywords
Myalgic encephalomyelitis Chronic fatigue syndrome Microbiota-gut-brain axis MetagenomicTopological data analysis Irritable bowel syndrome Metabolic pathway

https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y
 
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Cheshire

Senior Member
Messages
1,129
Article in The Times: https://www.thetimes.co.uk/article/gut-bacteria-linked-to-chronic-fatigue-30wkq5fjp (behind Paywall)

Couldn't prevent themselves from refering to "Yuppie flu":
Chronic fatigue syndrome has been linked to changes in the gut’s bacteria in the latest research showing that the condition once derided as “yuppie flu” has real physiological effects.

The scientists involved said that they were hopeful the work could lead to treatments for at least some of those suffering from the condition.


And link to the paper: http://download.springer.com/static...41fb5e8044a6194276c6f84b19b58b950f092764bb353
 

Cheesus

Senior Member
Messages
1,292
Location
UK
I really wish Lipkin's fundraising effort was doing better. His Monster Study would surely add heaps of useful data to existing literature. However the target amount is so high that it is simply daunting, and he is in direct competition with the likes of Ron Davis who has managed to capture the community's imagination more effectively.

Here's hoping he can get some money via the RFAs due in at the start of next month. Here is a link to make a donation:

https://giving.columbia.edu/giveonline/?schoolstyle=5881&alloc=21677
 
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I really wish Lipkin's fundraising effort was doing better. His Monster Study would surely add heaps of useful data to existing literature. However the target amount is so high that it is simply daunting, and he is in direct competition with the likes of Ron Davis who has managed to capture the community's imagination more effectively.

Here's hoping he can get some money via the RFAs due in at the start of next month. Here is a link to make a donation:

https://giving.columbia.edu/giveonline/?schoolstyle=5881&alloc=21677
Couldn't agree more about wanting more funds to go towards the work at CII (Centre for Infection and Immunity). Having said that, I haven't ever seen a total given for OMF, while the Microbe Discovery Project, who fundraise in support of CII, give occasional updates, and didn't Ron recently say that ideally he needs $5 million, which is the same target that MDP has? Of course, the ideal situation would be if both teams were properly funded.

From a recent MDP blog, http://microbediscovery.org/2017/02...l-this-mean-for-columbia-ciis-mecfs-research/
If the CII are successful with their RFA proposal the Microbe Discovery Project will still continue our fundraising efforts, with the same target of $5 Million. In total, $10Million would be required for CII to do the strongest and broadest range of analyses needed on all of the collected samples for the monster study and this does not even take into account other needed studies that they are seeking funding for. Researchers need far more than is forthcoming!
 

Manganus

Senior Member
Messages
166
Location
Canary islands
This is a press release from eureka Alert regarding a new publication from the Lipkin team at Columbia University

The conclusions are comprehensive:

Conclusions
Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
All very interesting but apart from obvious examples (dysentery) is there any evidence that the gut microbiota directly and unamiguously cause any disease?

This seems a more reasonable assessment (bold added) :

"The role of the microbiota in specific diseases and conditions

The above sections have described some of the many ways that the microbiota can influence human physiology, and it is no surprise that there is great interest in studying microbiota changes associated with diseased states, often referred to as dysbiosis (Table 1). However, the relationship between dysbiosis and disease pathogenesis is uncertain in the majority of examples at this time. It is often not clear what microbiota changes associated with disease are meaningful and distinguishing between cause and effect is inherently challenging. While it is intriguing to speculate that dysbiosis may cause disease as we learn more about how the microbiota can influence the host, it is also noted that the diseased state can lead to changes to the microbiota through various mechanisms, including changes in eating habits and bowel function as well as through the addition of medications such as antibiotics. In this section, we highlight a few of the recent findings on the role of the microbiota in particular diseases or conditions, but we cannot touch on all of the emerging findings in a multitude of other diseases both inside and outside the gut, including but not limited to rheumatoid arthritis (25), colorectal cancer (26), obesity (27), and diabetes (28)."

The gut microbiome in health and in disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290017/
 
ll very interesting but apart from obvious examples (dysentery) is there any evidence that the gut microbiota directly and unamiguously cause any disease?
And where does this paper make that claim?

From the paper, https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y, my bolding.
Conclusions
Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.

ETA: Associated does not equal caused by. There is a connection but they make no claim as to which way the link goes.
 
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Forbin

Senior Member
Messages
966
I really wish Lipkin's fundraising effort was doing better. His Monster Study would surely add heaps of useful data to existing literature. However the target amount is so high that it is simply daunting, and he is in direct competition with the likes of Ron Davis who has managed to capture the community's imagination more effectively.

Here's hoping he can get some money via the RFAs due in at the start of next month. Here is a link to make a donation:

https://giving.columbia.edu/giveonline/?schoolstyle=5881&alloc=21677

I agree. However, I suspect that using their resources to publish smaller studies like this may help them to bootstrap their way toward getting more sizable grants and getting the interest of additional donors. Hopefully, it will contribute to a process that will "snowball" in the future.
 

AdamS

Senior Member
Messages
339
From a brief scan it seems that some of the intestinal bacterial species that were seen to be increased are associated with the following:

- Increased fermentation
- Glucose tolerance/metabolism

Now i'm no expert but we already know from Davis/Fluge & Mella that there's something wrong with energy production and we seem to be falling back on the less efficient methods. Would it not make sense then to see increases in these bacterial species if we're having to rely on anaerobic respiration/fermentation more? 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! :)

9baazt.jpg
 

AdamS

Senior Member
Messages
339
@deleder2k Haha that's awesome. In all honestly i'm not entirely sure. There have been some theories thrown around that alcohol can help because of its vasodilatory effect. You would think that beer would be counterproductive though because of it's toxic load on the liver...it does contain a hell of a lot of sugar too. Some seem to be intolerant of alcohol and others get on fine with it which I find interesting.
 

Forbin

Senior Member
Messages
966
This study would seem to support the June 2016 study by Ludovic Giloteaux and Maureen Hason of Cornel University which found a decrease in the diversity of bacteria in the microbiomes of ME/CFS patients vs. controls.
https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4

Both studies found fewer bacteria of the type Faecalibacterium prausnitzii (F. prausnitzii), which apparently have anti-inflammatory properties.

Lower numbers of Faecalibacterium prausnitzii are also seen in Chron's disease and chronic ulcerative colitis, two inflammatory bowel diseases thought to be autoimmune in nature.
Association of Faecalibacterium Prausnitzii and Disease Activity in Ulcerative Colitis (May 2011)
CONCLUSION: A significant underrepresentation of F. prausnitzii was observed in UC patients when compared to healthy controls. We also observed an inverse correlation between the amount of F. prausnitzii and the disease activity. Our findings persisted, even after correcting for fecal water content. These results suggest that dysbiosis plays also a role in UC pathogenesis, and in particular points to the protective effects of F. prausnitzii against inflammation.
http://metcorner.gastro.org/article/S0016-5085(11)60576-3/pdf

Bacterium 'to blame for Crohn's' (October 2008)
Researchers believe the lack of a specific bacterium in the gut may be a cause of Crohn's disease.

A shortage of naturally-occurring bacteria is thought to trigger the inflammatory gastrointestinal disorder by over-stimulating the immune system.

Now a French team has highlighted the bug, Faecalibacterium prausnitzii, which they show secretes biochemicals that reduce inflammation.

The study appears in Proceedings of the National Academy of Sciences.

The researchers, from the Institut National de la Recherche Agronomique, had already shown that patients with Crohn's disease have a marked deficiency in bacteria from the Clostridium leptum group.

Their latest work shows that F. prausnitzii - a major component of this group - accounts for a large part of the deficit.
http://news.bbc.co.uk/2/hi/health/7679347.stm

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients
http://www.pnas.org/content/105/43/16731.abstract

[bolding mine]
 
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Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Wow, that's deep. What indeed is the point of this research, or any research for that matter?

Lighten up. It's a legitimate question and the first question that any funding panel member would ask. In fact they shouldn't/wouldn't need to as a funding application would state a working hypothesis (that ME/CFS will be found to be 'associated' with changes to the microbiome and that association is theoretically/clinically relevant because ....etc.

I expect they will state this in the full paper - I was hoping someone had an idea what their working hypothesis was.
 

AdamS

Senior Member
Messages
339
Both studies found fewer bacteria of the type Faecalibacterium prausnitzii (F. prausnitzii), which apparently have anti-inflammatory properties.

Hmm interesting. Looks like Faecalibacterium Prausnitzii could be quite relevant to us then. I've done a bit of digging and found this:
Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses
These mechanisms may contribute to the anti-inflammatory effects of F. prausnitzii in colitis and support the notion that this abundant bacterium might contribute to immune homeostasis in the intestine via its anti-inflammatory properties.

Cytokines-and-balance.jpg


Perhaps there is an argument to suggest that the microbiome could be a cause of ME then. If low Faecalibacterium prausnitzii (along with other changes to other bacterial species) can impact serum cytokine levels at such a 'high capacity' then maybe this could impact pyruvate catabolism and thus impact energy production. Again just throwing stuff out there, open to comments/criticism.

Source: https://www.nature.com/articles/srep18507
 
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