Dr Ian Lipkin's $1.27m gut microbiome study - crowdfunding campaign - news and updates

[aimossy]

Facebook:

ME/CFS stories:

The main reason that I’m keen on this research is probably the same as everyone else – recognition, effective treatment and cure. It seems to me that this research is on the right track in looking at bacteria, viruses and fungi. It seems to me that there must be something which is causing an upset in susceptible individuals and that the body’s stress response plays a part in allow...ing the culprit to do its mischief.

I feel especially sorry for the young people with ME and even if it’s too late for me, would like to see something which can help these people live a halfway normal life when they grow up, so they can study, achieve some of their dreams, have families and have the energy to look after and play with their children, travel, etc.

I’m 60 years old and live in Australia. I was diagnosed 5 years ago, when I was feeling unusually fatigued nearly all of the time and then pretty much ground to a halt, unable to get out of bed in the morning. In hindsight I realised that a somewhat similar crash I had in 2006 was the first major ME flare. About a year before this, in mid-2005, I developed unexplained skin rashes for weeks and felt under par, although not very sick. I think this may have been viral illness, and/or something picked up after being bitten by insects on holiday in New Zealand a few weeks earlier.

I was working as an IT business analyst/project manager when diagnosed. After long periods off work and then trying to return part-time, found that I couldn’t increase my hours and kept relapsing. I finally had to stop work in March 2013, claiming Total and Permanent Disability insurance.

Major impacts on my life have been having to give up work, most of a social life, and the ending of a long marriage. Fortunately I do have good friends who have stood by me, but on the whole I am much more isolated, not having the social interaction which came with my workplace (working as part of a team) and most of the time not being able to act spontaneously upon ideas to do interesting things with other people. Because of sensory overload, I can’t tolerate noisy or busy places for long at all without suffering ill effects and needing to lie down.
I think I am generally better now that I’m not working, but my activities have to be planned and limited. I think that the doctor estimated that I was functioning at about 20% capacity at the time I stopped work. I could be up to 30-40% these days, although it varies from day to day, week to week, month to month.

Fatigue and brain fog are probably the most debilitating.
Faecal analysis showed overgrowth of streptococcus and undergrowth of e.coli. Wishing you all the best and here’s hoping for at least one answer to part of the puzzle…
Kind regards, Anonymous
.......................................................................................................
Thank you so much for your story! We appreciate them greatly. So many people out there can identify and have untold stories. Hundreds of thousands of them--many do not even know they have ME/CFS. This illness has been ignored for too long and is a public health concern.

 

[aimossy]

Facebook: I couldn't get the image on here that was with this

Rachel Donahue, along with the "Make a Joyful Noise Studio" organized a benefit concert "Music for M.E.", which was hosted at Zionsville Fellowship Church, in Indiana. Children and adults played music for 2-3 hours, and raised more than $90...0 for Dr Lipkin's ME/CFS research.

Many thanks to the Zionsville Fellowship Church, and Rachel Donahue, and "Make a Joyful Noise Studio". And many thanks to the many volunteers who made the day happen, including Matt Beauchamp, Christine Jarrett (whose husband Tom has been ill with M.E. for 7 years) and others who played a big part in making the recital fundraiser a success.

Many thanks from all of us to everyone involved. This wonderful community effort will make a huge difference.

 

[aimossy]

There is 820 followers on Facebook.

 

[aimossy]

I'm just putting them up here so people on here don't miss out on things from FB.

This research article has some unfortunate terminology and may cause the odd grin for some

About 75% of the DNA analysed in human stool samples don’t match any known sequences in databases. A new analytical technique, known as 'cross-asse...mbly' developed at San Diego State University (SDSU) has enabled the discovery of a previously unknown bacteriophage, a type of virus that infects bacteria. The new virus has been dubbed crAssphage.

In a study by SDSU, crAssphage was present in three-quarters of the samples analysed and it accounted for 1.7% of all sequences, a percentage six times greater than all other known bacteriophages put together.

The team at SDSU think that the most likely 'hosts' for crAssphage are a group known as Bacteroides (symbiotic bacteria involved in digestion, the immune system and protection from pathogenic bacteria.) Changes in Bacteroides populations are thought to be linked to obesity and diabetes.

Dr Lipkin is looking for changes in populations of gut bacteria, viruses and fungi, and also looking for specific bacteria, viruses or fungi, that could be impacting in ME/CFS.
http://phenomena.nationalgeographic...eally-common-virus-only-just-been-discovered/

 

[aimossy]

latest Post on FB:

We have a video message posted to our page: Nicolette! You brave soul! Thank you so very much!

About the video she says:
This is a very non-scientific video from someone (me!) who is at the mercy of stalled scientific research and funding.... There are many, many more like me out there (17 million). While medications & research are constantly getting fast-tracked, Myalgic Encephalomyelitis (aka chronic fatigue syndrome) seems to get a big yawn from the medical & research community...and government agencies. Countless lives have been destroyed beyond measure by this misunderstood illness. Luckily, we have a number of doctors and researchers committed to getting toward some answers, toward a cure! But, here again, the NIH will not fund Dr. Ian Lipkin's proposed research project. All the while, Dr. Lipkin remains a renowned virologist and researcher. This is my private video message, my private appeal.
To donate directly: www.bit.ly/DonateToDrLipkin

https://www.youtube.com/watch?v=7iBJ9bzjppk

 

[aimossy]

From this link from IACFSME conference posters.
http://www.iacfsme.org/DesktopModules/DigitalDownload/2014Syllabus25.pdf

Altered Gut Microbiome in ME/CFS Patients in Comparison to Healthy Controls
Maureen R. Hanson1, Ludovic Giloteaux1, Julia K. Goodrich2, Susan M. Levine1,3, and Ruth E. Ley1,2
1 Cornell University, Dept. of Molecular Biology and Genetics, Ithaca NY, 2 Cornell University, Dept. of Microbiology, Ithaca NY, 3 Private Practice, New York City

Objectives. As well as the symptoms of fatigue, pain, malaise, immune dysfunction and exercise intolerance, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is associated with a variety of gastrointestinal complaints. In order to investigate the possible basis of this comorbid condition, we undertook a study to determine whether the gut microbiome in a ME/CFS population from the New York City area differs from healthy individuals.

Methods. We characterized the gut microbiota of a cohort of 48 patients with ME/CFS and 36 healthy controls from the New York City region by sequencing amplicons of the V4 region of 16S rRNA genes using the Illumina platform. Of the ME/CFS subjects, average age was 50.6 ± 13.3, 38 were female and 10 were male, while of the controls, average age was 46.5 ± 9.7, 29 were female, 7 were male. All patients fulfilled the Fukuda criteria for diagnosis of CFS. Levels of markers of inflammation, i.e. lipopolysaccharide (LPS), soluble CD14 (sCD14) and lactoferrin (LF) levels were also determined in plasma samples using standard assays.

Results. We obtained an average of 140,000 (± 86,000) high quality reads per sample. In both cases and controls, the most represented phyla were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Comparisons between cases and controls indicated a shift of diversity in the patient cohort. Statistical analysis revealed significant differences between groups, i.e. a reduction in members of the Bacteroidetes and an increase in members of the Firmicutes in the patient population, also reported in Crohn’s disease and acute ulcerative colitis. Specific species, including reduction of butyrate-producer Roseburia faecis (p = 0.001, q = 0.03) and increase of Ruminococcus spp. (p < 0.001, q = 0.004), were detected in subjects with ME/CFS. The amounts of LPS, sCD14 and LF in plasma in our cohort were not statistically different from controls and fell within normal ranges. Our data do not corroborate prior reports of significantly higher levels of Lactonifactor, Alistipes and Enterococci in the feces of patients.

Conclusion. Subjects with ME/CFS in our cohort have a shift in overall microbial composition in comparison to healthy donors, a finding also characteristic of patients with inflammatory bowel disease. Our analyses highlight the contrast between the distribution of anti-inflammatory species, such as Roseburia species, which are more prevalent in healthy individuals, and potentially pro-inflammatory Ruminococcaceae, which are associated with irritable bowel syndrome and found to be more frequent in ME/CFS cases. Despite the differences in gut microbiome, three inflammatory markers did not differ between patients and controls in plasma. Whether deliberate manipulation of the composition of the gut microbiome in ME/CFS patients may ameliorate symptoms in some patients remains to be investigated.

Maureen R. Hanson, Ph.D., Liberty Hyde Bailey Professor, Dept. of Molecular Biology and Genetics, Biotechnology Bldg., Ithaca, NY 14853 USA, mrh5@cornell.edu

 

[aimossy]

And this because it has Ian Lipkin in it. From the same link.
http://www.iacfsme.org/DesktopModules/DigitalDownload/2014Syllabus25.pdf

Allergy-related immune signatures and duration of illness in CFS
Susan Levine,1 Xiaoyu Che,2 Andrew F. Schultz,2 W. Ian Lipkin,2 Nancy Klimas,3 Lucinda Bateman,4 Dan Peterson,5 Donna Felsenstein,6 Elizabeth Balbin,7,8 Aundrea Carter,9 Korinne Chu,7 Mary Ann Fletcher,3 Anthony Komaroff,6 Gail Ironson7 and Mady Hornig2
1Private practice, NY, NY; 2Columbia U Mailman School of Public Health, NY, NY; 3Nova Southeastern U, Fort-Lauderdale-Davie, FL; 4Fatigue Clinic, Salt Lake City, UT; 5Simmaron Research Inst, Incline Village, NV; 6Harvard Med School, Boston, MA; 7U of Miami, Miami, FL; 8Miami VA, Miami, FL; 9U of North Carolina, Greensboro, NC; 10Physicians for Peace, Norfolk, VA

Objectives: Clinical features consistent with atopic and allergic disorders are reportedly more common among CFS patients. We sought to identify evidence for an enhanced allergic phenotype in CFS by comparing plasma levels of allergy-associated immune/inflammatory molecules in CFS patients with shorter vs. longer illness duration.

Methods: 293 CFS patients from two studies (NIH CFS and Chronic Fatigue Initiative studies) were pooled for analysis: 52 short duration (<3 years) and 241 longer duration subjects (>3 years). Plasma samples acquired at clinic visits were subjected to immune profiling analysis, and levels of allergy-related immune molecules were compared in short and long duration CFS.

Results: As compared with long duration CFS patients, patients with shorter illness duration had higher IL4 (p<0.001), IL13 (p=0.014), IL10 (p<0.001), IL6 (p=0.005), IL17A (p<0.001) and CCL5 (p<0.006). There was a trend toward lower eotaxin levels in the short duration subset (p=0.052). Short duration subjects also had elevations in other cytokines implicated in allergic responses, including IL1α, IL1β, IL1RA, IL8, MCP1, CXCL10, MIP1α, IL12p40 and TGFα (all p<0.002), as compared with longer duration CFS subjects.

Conclusion: Elevated levels of allergy-associated cytokines and chemokines in CFS of <3 vs. >3 years’ duration has led us to postulate a role for these mediators in producing allergic-type clinical phenotypes. Previous studies examining allergic disorders (asthma, allergic rhinitis) - often implicated as comorbid conditions in CFS - support the presence of elevated plasma IL4, IL5 and IL17. Our finding of elevated levels of molecules involved in the allergic diathesis, including IL4 and IL17A as well as IL6, IL8, IL10, and eosinophil-recruiting chemokines such as CCL5, lends support to the hypothesis of a Th2 shift with a distinct immune signature in a subset of CFS. IL4 produced by basophils following encounters with allergens leads to T cell differentiation and IL17A production; IL17A in turn recruits eosinophils, mast cells, neutrophils and other cell types that then produce IL6 and IL8 in addition to other allergic mediators.Elevated plasma eosinophil cationic protein has been reported in a group of CFS patients, but few other studies have investigated the role of allergic mediators. Our findings suggest pathways for possible therapeutic intervention and clinical trials. Leukotriene inhibitors used to treat asthma that reduce plasma IL-4 could potentially play a therapeutic role in certain CFS subsets. The unique immune signature found in our short duration subjects suggests at least one important pathophysiologic mechanism by which we can begin to understand the allergic CFS phenotype. The influence of eosinophil and basophil levels, age, level of disability, comorbidity, heritable conditions, ethnicity, sex and geographic site will be examined in addition to temporal and seasonal changes in the allergy-related cytokines/chemokines. Future studies should include determinations of levels of histamine, total and specific IgE, prostaglandin E2, tryptophan and serotonin, in addition to comparisons with healthy controls.

Presenting author: Susan Levine, MD; Physician in private practice, address: 115 East 72nd St, Suite 1A, NY NY 10021 USA; email:

 

[aimossy]

Another poster from same link: with Ian Lipkin and Mady Hornig in this one.
http://www.iacfsme.org/DesktopModules/DigitalDownload/2014Syllabus25.pdf

Immune signatures associated with cognitive dysfunction in CFS

Mady Hornig,1* Xiaoyu Che,1 Andrew F. Schultz,1 Susan Levine,2 W. Ian Lipkin1 and the CFI Study Group 1Columbia University Mailman School of Public Health, NY, NY; 2Private practice, NY, NY

Objectives: Mental fatigue, memory deficits and perceptual processing problems are major contributors to dysfunction in CFS, but the severity of cognitive disturbance varies both within individuals over the course of illness and across phenotypic subsets. Access to a robust biomarker of cognitive dysfunction in CFS would accelerate identification of patients responsive to select treatment strategies and also provide clues to pathogenesis. Although cytokine disturbances are reported in many CFS investigations, study populations and findings are heterogeneous, limiting their utility as biomarkers. We used feature selection and 51-plex immunoassays in an effort to define immune signatures associated with cognitive deficit in CFS.

Methods: Data from 298 CFS and 348 control subjects from the NIH CFS and the Chronic Fatigue Initiative studies, frequency-matched on age and gender, were pooled. High/low cognitive impairment subgroups were established using mean scores for 4 mental fatigue items from the Multidimensional Fatigue Inventory (MFI4, cases and controls; cutoff 1 SD > population mean): 142 high/147 low MFI4 cases; 29 high/312 low MFI4 controls. Plasma samples were subjected to immune profiling analysis. Principal components (PCA) and partial least square (PLS) feature selection approaches were applied to the 51-cytokine data set to derive latent variables for application as independent variables in logistic regression. Cytokines with odds ratios (OR) >1.1 or <0.9 (p<0.05) by PCA or PLS for the association with high MFI4 subgroups were included in the final logistic regression model along with age as a covariate.

Results: Elevated IFNγ levels were strongly associated with cognitive impairment in cases (high MFI4) (OR, 67.42; 95% CI, 5.34, 850.83; p=0.0011). Increased CXCL1 levels were also associated with more impaired case MFI4 (OR, 1.23; p=0.0285), with a trend in the same direction for IL13 (OR, 1.26; p=0.08). The pattern within controls was similar to that within cases for IL13, with elevated levels predicting greater cognitive impairment (OR, 1.71; p=0.0088); however, other cytokines associated with cognitive impairment among cases did not show a similar pattern among controls. Stratified analyses showed no relationship with sex.

Conclusion: Cognitive dysfunction in CFS is associated with specific patterns of elevated cytokines. Increased circulating levels of IFNγ have a striking relationship with cognitive impairment. Individuals with CFS but without cognitive dysfunction did not demonstrate these disturbances. These results suggest immune homeostasis may be dysregulated in the subset of subjects with CFS with prominent cognitive disturbance. IFNγ elevations among cases with cognitive impairment may point toward a subgroup with higher probability of viral triggers and/or persistent infection.]

 

[aimossy]

Apologies if I hijacked thread throwing so much on here.

 

[aimossy]

Facebook:

Considering what Dr Lipkin and Dr Hornig are wanting to research in ME/CFS - this is very interesting. Here is a summary article integrating two new research papers:
Is the gut microbiome a potential therapeutic target for autoimmune diseases like multiple sclerosis?

Abstract:
Numerous risk factors are believed to contribute to the development of autoimmune disorders such as multiple sclerosis, and new research is focusing on the role that bacteria in the gastrointestinal tract as well as other cell stress-related chemical signals could have in stimulating inflammation in the central nervous system and activating immunostimulatory cytokines. Two comprehensive Review articles are part of a focus on "Cytokines in Neuroinflammation and Immunity" in a special issue of Journal of Interferon & Cytokine Research (JICR), a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The articles are available free on the JICR website.

http://www.eurekalert.org/pub_releases/2014-08/mali-itg080714.php#.U-TU-LDzU6c.twitter

 

[Bob]

The Team are absolutely delighted!
Dr Anthony L. Komaroff, Professor of Medicine at Harvard Medical School, has donated to the crowdfund appeal and sent us a donation message.

https://www.facebook.com/microbedis...41830.629692043766500/698490590219978/?type=1

 

[Bob]

Today's Crowdfunding Update.

The latest crowdfunding total is:

$110,675 from 504 donations.

Thanku to everyone!

 

[Bob]

Today's Crowdfunding Update.

The latest crowdfunding total is:

$111,446 from 510 donations

Thanku to everyone!

 

[Bob]

Today's Crowdfunding Update.

The latest crowdfunding total is:

$111,526 from 511 donations

Thanku to everyone!

 

[aimossy]

From Facebook

TOUR OF THE MICROBIOME HQ

Recently a member of our (tiny!) team was in New York and had the privilege of visiting the Center of Infection and Immunity at the Columbia University Mailman School of Public Health, where Dr. Lipkin and his 60-...strong team will conduct the study crowdfunded for by the Microbe Discovery Project. This is their report:

I went to CII today. They were fantastic. I only gave them two days’ notice but from 4-5:30pm, they managed to squeeze me into seeing the lab, Dr. Lipkin and also Allison Kanas.

Lorenzo (Dr. Uccellini), one of their ME/CFS researchers, showed me around the huge labs--spread across two floors--and I saw some of the high-tech kit that will be used in the microbiome study (check out the attached photos). And I met several other researchers who would also be involved in the study.

After the lab tour I was directed straight to Dr Lipkin's office (where ironically he was having some sort of virus). He told me about some exciting developments in the research that the team is already doing under the Chronic Fatigue Initiative-- developments which could steer the direction of the crowdfunded study.

Then it was off to see Allison Kanas (Director of Strategic Initiatives & Planning of the CII). She and her team are pursuing some exciting plans to greatly increase publicity of ME/CFS in the near future as a legitimate disease that is extremely worthy of research funding, not only from within but also from outside the patient community.

This visit gave me a tremendously exciting peek into the state-of-the-art facilities and it was great to meet some of the excellent researchers who would be working on the microbiome study. I'm really excited about this study and hope we can all make it happen. Thank you Drs. Lipkin, Hornig and Allison Kanas for everything!

I hope you enjoy the photos--a mini virtual tour of the microbiome study HQ.

 

[aimossy]

Photos from Facebook:

 

[Sasha]

Here's the link to the FB page where the photos are a bit bigger:

https://www.facebook.com/microbediscovery/posts/699976286738075

Sounds like there are some exciting findings and exciting plans coming down the pipeline!

 

[aimossy]

Sorry, I thought people could click on them to make them larger. tehe

 

[Sasha]

Sorry, I thought people could click on them to make them larger. tehe

Ooh! You're right, we can!

 

[misskatniss]

And I suggest many people out there click on the donation button to make the amount bigger too ... Oh, hopefully something helpful turns out from the study, and hopefully the funding´s enough soon!