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Lipkin's Microbiome Research -- new or old topic? (split thread)

Daffodil

Senior Member
Messages
5,875
Hi Daffodil.

I totally agree with you... As far as I understand, KDM sees that most PWCFS have Lyme, and that Lyme, interacting with the TCR receptor (and probably by other indirect routes), contributes to this negative vicious cycle, that IS NOT NEW. The new thing here is to have found that ONLY the macrophages of the gut, known as plasmacitoid dendritics cells, are the ones expressing HERV proteins, and ONLY in PWCFS and not in ANY healthy control... This is important to highlight! We have a specific cell to look at, in the gut!!! This is big, and it is a fact. The flaw is the low number of participants in the study...that's why we need another study to confirm it!, then the pharmaindustria will have a very very sweet candy to put money in... But only if another team, and if possible with higher "n", replicates the results.


BTW, could you please give me the link of this study about influenza??


Thank you!

Sergio


sure, here is the abstract:

http://www.ncbi.nlm.nih.gov/pubmed/24478419
 

serg1942

Senior Member
Messages
543
Location
Spain
Thank you Daffodil!

I just wanted to make a final reflection on the subject: When XMRV was found in PWCS and published in Science, most of us agreed that the next step forward was necessarily to replicate that study. It was so obvious. If it could be replicated, then there would be trials for drugs, a reliable test, etc., etc.

OK, this is kind of the same, and even better in one way: They've learned from the past. The know XMRV was an antiretroviral sequence, but were wrong about the name and about the origin... But it was a retroviral sequence after all...

Ok, what's the difference?? that they have not found an specific HERV yet, that the number of patients and controls are much more smaller, and than the journal is not Science. But the gist, is the same if not better: They have found HERV proteins acting as superantigen; It is known what they cause, and it totally would fit with CFS. And moreover, they have found the cells expressing these abnormal proteins ONLY in CFS...

Remember: In the first XMRV-CFS study they didn't find the resident cells nor the pathogenic mechanism for XMRV. Well, they have now found both for the HERV yet to be identified.

Really, this is as big as XMRV, with more caution and with more knowledge having learned from the past.

So, It is so obvious for me, that the efforts of scientists an doctors should go in the direction of either confirm or not these findings. As important as it was before...

Best,
Sergio
 

vli

Senior Member
Messages
653
Location
CA
Just so everyone knows, I am by no means against the KDM work--why else would I be here asking you all to explain the HERV work to me??? And after hearing you all, I think this is extremely promising. You've got my saying that on record.

But to put it bluntly, KDM has money. Now nobody has said that to me, but a) he didn't make an appeal to the public for funds, and b) he's already doing the work now (as @serg1942 and @Daffodil you've told me on this thread). So where could he be getting the money to do this work? He hasn't asked people; it must be a grant.

This thread was split off from the original Lipkin thread because people were saying funds should be given to the WPI. Well as we've seen, not only is no one PREVENTING anyone from giving to the WPI, but that in fact KDM already has the money to do the work that all his supporters are saying should be done (otherwise, hey, he wouldn't now be doing it). So to put it bluntly, what's the problem?

btw I'd still really appreciate an answer to the question I asked before below. as far as I am aware, no one has been able to answer me.
I disagree. IF enteros ARE the trigger for the HERV expression, wouldn't you want to turn them off??? I understand that the goal is to develop a drug that will stop the HERV expression but I am not sure it is so easy to turn off HERVs all over the body.

Maybe there are two points of attack here: you can develop a drug to stop the HERV from being expressed, or a drug that stops the thing that's triggering the expression in the first place (the actual cause of the pathology).
 

serg1942

Senior Member
Messages
543
Location
Spain
VLI:

Straight to your question: that's the thing. What we need is a different team trying to replicate this study. So if the WPI with KDM and Lombardi and the rest of the team are working on something, great! But We need a different team working on this. In other words, if we can make that Lipkin (for example) tries to replicate this study instead of the microbiome one, I think that money would be invested in a better way (this money, and of course, any other funds directed to other issues nothing to do with this...)

As for your other question: If enteroviruses would be triggers (we don't know that, they could be just opportunistic as most of the "bad bugs"), they would be the same as HHV-6, or EBV (probed to actually be triggers). Do people in general get cured treating these viruses?: No.

Finally, sure Vli, there'd be two ways to treat this: inhibit the specific HERV (this is what we need to research...), and what we are doing at the moment, that is, to treat the terrain (antivirals, ABX, GcMAF, gammaglobulines, improve the microbiome, lower the toxic load, improve the redox status--methylation, NO/ONOO- cycle, support the mitochondria, etc.).

Treating the terrain gives a variety of results. Some patients improve nothing, some a little, some a lot, and few get "cured" (while they continue treatment forever). Also these treatments are outrageously expensive..., not available for most.

On the other hand, treating the cause, the potential HERV that could be the very core of the pathogenesis of CFS, would lead us to: 1- reliable and international test for CFS, 2- Be attractive to the pharma-industry, what means money, BIG trials, possible real drugs/treatments, and of course recognition of the disease as we deserve.

This is my humble opinion. Hope it is helpful.,
Sergio

PS- I've highlighted the important things of the text in order to be easier to read for our fellows. Not trying to emphasize my ideas because I think I am right, or something like that. People may get offended with uppercase or bold letters, so I better explain.
 

vli

Senior Member
Messages
653
Location
CA
OK @serg1942 I think this is my problem. Please understand that I am only trying to understand!!!

BECAUSE enteroviruses are from outside the body, Chia and others should NOT have found them in his biopsies of ME patients. What does this tell me? This tells me that I THINK, although I am not sure of course, that HERVs are not the "first cause" of the pathology. Like I said: HERVs are being expressed, so something has to be making them to be expressed, and that something is the "first cause" of the pathology, not the HERV. Why has treating EBV and HHV6 not succeeded in stopping the HERV expression? Well to me that shows that they're not the "first cause".

Right now, however, we don't know whether enteroviruses are the first cause (remember I did not say that I know, just that I think it is possible). And if research can prove that they ARE the cause of the HERV expression, then enteros are not the same as infections like EBV or HHV6.

As for Lipkin: actually, when I was asking Simon McGrath to interview Lipkin to write the Phoenix article, I discussed with him if there was some way we could ask Lipkin why he didn't do a different study (such as your suggestion of replicating KDM's work). But I was told the answer that we, are hardly in a position to tell Lipkin (or any researcher) what study to conduct. Yes, I will say this, in an ideal world I would ask Lipkin why he doesn't collaborate with KDM or try to replicate his work, but in reality I'm sure you know I cannot do that; and don't forget, if I did not contact Dr Lipkin at all, then zero dollars would be spent on ANY work, that still would not increase/decrease the amount of funds given to KDM research. Do you see what I mean? If Lipkin doesn't spend a million on studying the microbiome, it doesn't add more to KDM's funding; if he does spend a million on the microbiome, it doesn't DECREASE the funds for KDM's work. Can anyone try to tell me otherwise?? That the Lipkin appeal is somehow taking money AWAY from KDM (when KDM has a grant)???
 
Last edited:

Jon_Tradicionali

Alone & Wandering
Messages
291
Location
Zogor-Ndreaj, Shkodër, Albania
@vli @serg1942

Below is an extract of a post I made on my thread a few days ago regarding dendritic cells of the gut:

-----------------------------------------------------------------------------------------------------------------------------------------------
A reason why pathogenic bacteria cannot be cleared using antibiotics. In cases that they are cleared, a relapse occurs shortly after:

"High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103(+)CX3CR1(-)CD11c(+) dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate.....Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. "

http://www.ncbi.nlm.nih.gov/m/pubmed/24558351/?i=2&from=bacteria lymph

The ability of bacteria to infect the dendritic cells of the gut and thus avoid detection by the immune system is very plausible.

Dendritic cells are the guts screening system to identify the different bacteriae passing through as pathogenic or non pathogenic.

For the bacteria to infect these cells provides a perfect explanation why the immune system cannot locate them.
---------------------------------------------------------------------------------------------------------------------------------------------------

You must notice, not only viruses can be responsible for triggering HERV expressions.
According to KDM, Streptococcus and Enterococcus are highly over-represented
in ALL PWCFS versus controls.

I feel we are almost there.
 

serg1942

Senior Member
Messages
543
Location
Spain
VLI:
1. If it is not possible to influence Lipkin to do other research than the microbiome, where's the point of asking our opinion? If he is going to do either this one, or none, then go ahead... Why are we discussing this in the first place? (I am delighted of giving my opinion, but, I thought it could make at least a tiny tiny tiny difference...)

2. First cause? Vli, normally there could be like 100 first causes and 100.000.000 combinations between them, in order to put in motion and perpetuate a pathogenic vicious cycle. The important thing is not the trigger, but the triggered mechanism... An clear example: cancer.

You need what is called an iniciator plus a promotor in order to provoke mutations (normally more than 5), in order for a cell to become cancerous. There could be millions and millions of iniciatiors and promotors... They are the triggers... But what really matters is the cancer (triggered mechanism). You can see in this example that triggers are useful to prevent the cancer, but once the cancer has appeared, then what only matters is the cancer itself, right? Well, the very same should be extrapolated to the subject we are talking about.


You must notice, not only viruses can be responsible for triggering HERV expressions.
According to KDM, Streptococcus and Enterococcus are highly over-represented
in ALL PWCFS versus controls.

I feel we are almost there.

Jon, this abstract is great! thank you!

Best!
Sergio
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
Lipkin and Columbia have, and are, doing more than the research project on the Microbiome. If you want them to consider another study, then I suggest you draft a question - along the lines of 'do you think it is possible that this could be happening....' and 'would you consider a replication study....' and include reference to the research from KDM and Lomardi that you evidently think is so good. I - or Vanessa - would gladly pass it along as a general enquiry. I have said similar on another thread and in relation to Chia's work - which again others think deserves replication.

This Microbiome work is different. It is a stand alone piece of research and shouldn't be considered as encroaching on - or taking away - the chance to replicate other people efforts. If Chia, Lombardi or KDM want their work replicated - they can contact Lipkin themselves or - in the case of Chia - apply for more funding. But they can and should also consider other people to do this work too.

The onus in on those researchers to move their initial work along. The Microbiome work is a work of discovery - to try and see what is in our guts that is not in other peoples who do not have our diagnosis. To observe patterns. There is enough diets, supplements, theories, and potions available to and taken by people with our condition - that we really do need some solid research into this area.

There is immune activation being observed - we know this - we will hear more about the evidence found in Lipkins work with Montoya and Peterson et al on the blood, when the paper is finally published. They couldn't discover a source for this activation in the blood or spinal fluid, so let's look in the Microbiome. If they can discover a reason (or reasons) for what might be activating the immune system and causing the symptoms (or some of them) that are a feature of ME, then we could have some answers to at least part of the puzzle for some of us.

It isn't a competition. Research can and does run in parallel. And frankly the more, good quality, research the better.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
It isn't a competition. Research can and does run in parallel. And frankly the more, good quality, research the better.

True - and the high profile of Lipkin means that by fundraising for his study, we'll grow the base of donors so that all future ME research fundraising can benefit. The advantages of a fundraising campaign for the Lipkin study go well beyond that study itself.

Like I keep saying, a rising tide floats all boats! :)
 

Wally

Senior Member
Messages
1,167
Lipkin and Columbia have, and are, doing more than the research project on the Microbiome. If you want them to consider another study, then I suggest you draft a question - along the lines of 'do you think it is possible that this could be happening....' and 'would you consider a replication study....' and include reference to the research from KDM and Lomardi that you evidently think is so good. I - or Vanessa - would gladly pass it along as a general enquiry. I have said similar on another thread and in relation to Chia's work - which again others think deserves replication.


FYI - http://www.mailman.columbia.edu/our-faculty/profile?uni=wil2001

Dr. Ian Lipkin
wil2001_3_LipkinProfilePhoto.jpg



Contact Information

Office/Address:

Center for Infection and Immunity, 722 West 168th Street, Room 1703a

New York, NY 10032

USA

Website Address:

Homepage URL

Phone:

212-342-9033

Fax:

212-342-9044

E-mail:

wil2001@columbia.edu
 

serg1942

Senior Member
Messages
543
Location
Spain
I have just been asked to give reasons as to why I think money should be invested in HERV's work instead of in microbiome. And so I have written my thoughts.

I am an activist on CFS, but my field of expertice is not raising funds. I study medicine, run a Spanish CFS-investigation forum, I'm a member board of a CFS-related Spanish national association... So, it's not my purpose to convince anyone to direct his/her research into a certain direction. I try to help by other means...

I just gave my opinion, that is not better than anyone's. Of course, the more studies the better...Obviously.

Best,
Sergio
 

Daffodil

Senior Member
Messages
5,875
@vli @serg1942

Below is an extract of a post I made on my thread a few days ago regarding dendritic cells of the gut:

-----------------------------------------------------------------------------------------------------------------------------------------------
A reason why pathogenic bacteria cannot be cleared using antibiotics. In cases that they are cleared, a relapse occurs shortly after:

"High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103(+)CX3CR1(-)CD11c(+) dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate.....Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. "

http://www.ncbi.nlm.nih.gov/m/pubmed/24558351/?i=2&from=bacteria lymph

The ability of bacteria to infect the dendritic cells of the gut and thus avoid detection by the immune system is very plausible.

Dendritic cells are the guts screening system to identify the different bacteriae passing through as pathogenic or non pathogenic.

For the bacteria to infect these cells provides a perfect explanation why the immune system cannot locate them.
---------------------------------------------------------------------------------------------------------------------------------------------------

You must notice, not only viruses can be responsible for triggering HERV expressions.
According to KDM, Streptococcus and Enterococcus are highly over-represented
in ALL PWCFS versus controls.

I feel we are almost there.


Jon..love your post. it is entirely possible for bacteria to be the cause of the HERV expression, it is true. my question is....would the microbiome study be able to tell us if bacteria in the plasmacytoid dendritic cells are responsible for the HERV expression?

thanks
xo
sue
 

Daffodil

Senior Member
Messages
5,875
upsetting that they won't just try to replicate KDM's work first. everyone wants to do original work for obvious reasons; this is life or death for some of us and it just is not fair
 

bel canto

Senior Member
Messages
246
This is a bit off-topic, but seems related. Researchers recently linked a bacteria to multiple sclerosis:

"The researchers hypothesize that after a human is infected with C. perfringens B or D, the bacterium can reside in the gut as an endospore, defined as a "seed-like structure" allowing certain bacteria to stay dormant for long periods.

"The human gastrointestinal tract is host to approximately 1,000 different bacterial species, but is not a hospitable environment for C. perfringens type B or D, so it does not grow well there," explains Dr. Timothy Vartanian, professor of neurology and neuroscience at Weill Cornell Medical College and senior study author.

"It hibernates in a protective spore. When it does grow, we anticipate it generates a small quantity of epsilon toxin, which travels through the blood into the brain."

He adds that they believe the bacterium's growth is always present, but "rears its ugly head from time to time."

http://www.medicalnewstoday.com/articles/267676.php

There have also been numerous findings related to MS and HERV's.
 

vli

Senior Member
Messages
653
Location
CA
Jon..love your post. it is entirely possible for bacteria to be the cause of the HERV expression, it is true. my question is....would the microbiome study be able to tell us if bacteria in the plasmacytoid dendritic cells are responsible for the HERV expression?
I believe that you said here that you did not personally think it was important what it was that triggered the HERV expression, after I said that Chia showed that enteroviruses were good candidates.
 

Daffodil

Senior Member
Messages
5,875
hi vli. what I meant is, it is possible that the bacteria is an ongoing problem, causing the HERV to continually be expressed. for me, the trigger was EBV. I am just guessing here.