Lipkin's new microbiome study, "Fecal metagenomic profiles in subgroups of patients with ME/CFS"

[Anomie]

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

 

[Anomie]

Update: the full study has now been published in Microbiome:

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

 

[Remy]

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 Bacteroides abundance 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.

 

[Remy]

PUBLIC RELEASE: 26-APR-2017
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
COLUMBIA UNIVERSITY'S MAILMAN SCHOOL OF PUBLIC HEALTH

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
  

"Individuals with ME/CFS have a distinct mix of gut bacteria and related metabolic disturbances that may influence the severity of their disease," says co-lead investigator Dorottya Nagy-Szakal, postdoctoral research scientist at CII.

"Our analysis suggests that we may be able to subtype patients with ME/CFS by analyzing their fecal microbiome," says co-lead investigator Brent L. Williams, assistant professor of Pathology and Cell Biology at CII. "Subtyping may provide clues to understanding differences in manifestations of disease."

"Much like IBS, ME/CFS may involve a breakdown in the bidirectional communication between the brain and the gut mediated by bacteria, their metabolites, and the molecules they influence," says senior author W. Ian Lipkin, director of CII and John Snow Professor of Epidemiology at Columbia's Mailman School. "By identifying the specific bacteria involved, we are one step closer to more accurate diagnosis and targeted therapies."

###​

The study was supported by the Chronic Fatigue Initiative of the Hutchins Family Foundation; the National Institutes of Health Center for Research in Diagnostics and Discovery (AI109761); John, Cynthia, and Lisa Gunn; and anonymous donors through the Crowdfunding Microbe Discovery Project.

Additional co-authors include Nischay Mishra, Xiaoyu Che, Bohyun Lee, Komal Jain, Meredith L. Eddy, and Mady Hornig at CII; Lucinda Bateman at the Fatigue Consultation Clinic, Salt Lake City; Nancy G. Klimas at Nova Southeastern University; Anthony L. Komaroff at Harvard Medical School; Susan Levine at Levine Clinic, New York City; Jose G. Montoya at Stanford University; Daniel L. Peterson at Sierra Internal Medicine, Incline Village, NV; and Devi Ramanan at Ayasdi, Inc., Menlo Park, CA.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
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[Remy]

This part about no difference in cytokine levels is disappointing and frustrating to me because I really think access to some of the newer monoclonal antibody treatments might be helpful.

Plasma cytokine concentrations do not distinguish ME/CFS groups

Immune profiling (Additional file 1: Table S4A) was performed to test for alterations in the ME/CFS and IBS subgroups. No significant findings were obtained after adjusting for multiple comparisons of all 61 cytokines. However, prior to adjustment, TNF-α was increased in the ME/CFS cases compared to the controls (Additional file 1: Table S4B) and plasma levels of leptin, CSF-2, CXCL-8, and TNF-α were higher in the ME/CFS + IBS patients than the controls (Additional file 1: Table S4B). The ME/CFS patients without IBS had a pre-adjustment trend toward increased TNF-α compared to controls.

Unsupervised hierarchical clustering was used to visualize the variation in plasma cytokine levels between the total ME/CFS, ME/CFS + IBS, ME/CFS without IBS, and controls. Although the clusters did distinguish a range of cytokine profiles in individuals (ranging from high to low cytokine profiles), there was no distinct clustering observed between disease groups (Additional file 2: Figure S2).

 

[Remy]

http://microbediscovery.org/2017/04...eria-in-mecfs-may-influence-disease-severity/

• • Levels of distinct intestinal bacterial species—Faecalibacterium, Roseburia, Dorea, Coprococcus, Clostridium, Ruminococcus, Coprobacillus—were strongly associated with ME/CFS; their combined relative abundance appears to predict if someone has the illness.

  • Increased abundance of the Alistipes group of bacteria, and decreased Faecalibacterium were the top biomarkers of ME/CFS with IBS.

  • Enrichment in the pathway for vitamin B6 biosynthesis and salvage (i.e. recycling B6) was the strongest predictor of ME/CFS, regardless of whether or not patients had IBS. Vitamin B6 helps the body use and store both proteins and carbohydrate, as well as help form the haemoglobin that carries oxygen round the body. There is some evidence B6 is low in patients, but this could be down to changes in the body rather than in gut bacteria.

  • No changes were observed in immune markers which may reflect the lack 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

 

[madie]

In Cort's article Ian Lipkin says “The ME/CFS community is very eager to find solutions. I expect there will be people immediately trying to modify their microbiota. In the end we think all this needs to be done in a full clinical trial but there will be people acting on this.”

Yes, that's me! I'm already wondering how to experiment with this. Anybody got ideas?

 

[rebar]

I'm starting to look more closely at Ken's work, my gut needs serious help, and his approach makes a great deal of sense. Using pub-med as a resource for treatment.

Below is his take on the latest Lipkin study.


https://cfsremission.com/author/lassesen/

 

[Remy]

I'm starting to look more closely at Ken's work, my gut needs serious help, and his approach makes a great deal of sense. Using pub-med as a resource for treatment.

Below is his take on the latest Lipkin study.


https://cfsremission.com/author/lassesen/

Great blog post!

I use acarbose to help manage blood sugar and it works really well. The only side effect is some increased gas after eating a lot of veggies but I just blame that on the dogs.

 

[Ian Mills]

Yes, that's me! I'm already wondering how to experiment with this. Anybody got ideas?

Fecal transplants. People have tried it both orally and anally. Here is the story of one person who has had success using the enema version:

https://www.reddit.com/r/cfs/comments/67udpu/fmt_has_completely_cured_my_ibs_and_cfs_could_be/

 

[Merida]

I found some B.S. with out the I part : "ME/CFS and its underlying pathology or the emotional response to illness in these individuals may predispose ME/ CFS sufferers to IBS."

Oh S***. Literally and figuratively. IBS is a very poorly defined disorder to begin with. I spent 15 years with this diagnosis ( at large university research group) Despite having a a dx of possible tethered cord syndrome ( from the neurosurgeon who defined the pathophysiology of thus disorder!!! ) and a long, redundant, tortuous colon. Just by 'luck' ( if you can call it that) I developed solitary rectal ulcer syndrome - my colon was telescoping. This is difficult to diagnose , as on colonoscopy the bowel is filled with air and the telescoping is not occurring.

A long redundant colon has been considered an incidental finding, but I found one article where researchers felt it was the result of a malrotation/ malattachment phenomenon. This is important, as there can be abnormal bands of soft tissue that can be present and hold the colon in an abnormal position.

So, how many of us have been diagnosed with a long,redundant colon ?
it is not benign and incidental, especially when the neurology takes a hit.

 

[Hustler]

U think Lipkin will find a retrovirus in all that poo ?

Or do u think he ll just find his own ass?

 

[laureano]

I found some B.S. with out the I part : "ME/CFS and its underlying pathology or the emotional response to illness in these individuals may predispose ME/ CFS sufferers to IBS."

Oh S***. Literally and figuratively. IBS is a very poorly defined disorder to begin with. I spent 15 years with this diagnosis ( at large university research group) Despite having a a dx of possible tethered cord syndrome ( from the neurosurgeon who defined the pathophysiology of thus disorder!!! ) and a long, redundant, tortuous colon. Just by 'luck' ( if you can call it that) I developed solitary rectal ulcer syndrome - my colon was telescoping. This is difficult to diagnose , as on colonoscopy the bowel is filled with air and the telescoping is not occurring.

A long redundant colon has been considered an incidental finding, but I found one article where researchers felt it was the result of a malrotation/ malattachment phenomenon. This is important, as there can be abnormal bands of soft tissue that can be present and hold the colon in an abnormal position.

So, how many of us have been diagnosed with a long,redundant colon ?
it is not benign and incidental, especially when the neurology takes a hit.

I know a teenager who got diagnosed with abnormaly long colon and whose only symptom was constipation. I just don't buy it, there must be and underlying cause for that symptom of hers