Our microbiomes are clearly very important, but they don’t come close to explaining why you get MS and whether or not one of our microbiomes is causal in MS. Yes, there are multiple microbiomes in and on our bodies. At the moment the attention is all focused on the gut microbiome, in particular, the distal colon. Why? Because it is easy to collect poo samples. But why the colonic microbiome in MS and not another site?
If I had the time and interest I would focus on other sites, in particular, the paranasal sinuses and lungs. There is a hypothesis that infections in the paranasal sinuses are more common in MSers and can trigger MS. There is some evidence, albeit weak, that MSers are more likely to have had sinusitis than control subjects. What organisms are causing these episodes of sinusitis?
The other site is the lungs. Smoking and solvent exposure increases your risk of getting MS. It does not appear to be tobacco itself which is the risk factor because the oral use of tobacco is not associated with an increased risk of getting MS. In fact, oral tobacco use appears to lower the risk of getting MS. The overlap between smoking and solvents could be via the microbiome in the lung and/or lower respiratory tract.
For me, the most exciting data points to our internal or systemic microbiome, i.e. the viruses and bacteria that live within our bodies. EBV is an exogenous virus that lives with our bodies; in fact inside memory B-cells the major therapeutic target of our treatments. The evidence for EBV being the cause of MS is so overwhelming that we are planning an anti-EBV vaccine prevention trial and we are also exploring anti-viral strategies against EBV.
How EBV causes MS is unknown, but one hypothesis is via its induction of HERVs (human endogenous retroviruses). EBV simply wakes-up, or resurrects, these dormant viruses which then activate the immune system and trigger autoimmunity. This is why we are so keen to target HERVs with antivirals as a treatment strategy for MS.
But getting back to the gut microbiome. In my opinion, it is simply the latest research bandwagon with everyone making premature claims that by manipulating it we may be able to prevent people from getting MS in the first place. Or alternatively, once you have MS we may be able to treat your disease by manipulating the microbiome with diet or by providing you with ‘good’ bugs. This has resulted in a new generation of quacks offering vulnerable MSers faecal transplants to ‘treat’ and ‘cure’ them of having MS. There is simply zero evidence to support these claims so please avoid being hoodwinked into having a faecal transplant, which may be dangerous.
The following microbiome paper is interesting and shows that (1) daily microbiome variation is related to your food choices, but not to conventional nutrients, (2) daily microbiome variation depends on at least two days of dietary history and most importantly (3) similar foods have different effects on different people’s microbiomes. Therefore, there will be no magic bullet bacterial pill, super-poo transplant or some superfood diet that will necessarily alter your microbiome.
My advice is to eat well and eat sensibly, real-food rather than processed food, and get off the microbiome bandwagon until some class 1 evidence emerges to contrary.
Johnson et al. Daily Sampling Reveals Personalized Diet-Microbiome Associations in Humans. Cell Host Microbe. 2019 Jun 12;25(6):789-802.e5.
Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477.
Sorry, this comment has nothing to do with the gut microbiome but rather with your observations regarding EBV and endogenous retroviruses.
If EBV does in fact activate (upregulates) one or more of these retroviruses embedded in the human genome, wouldn’t a strategy to deactivate this viral genetic material be more effective than using antivirals? In other words, could some sort of gene therapy that down-regulates EBV upregulated endogenous retroviruses be the key to stopping the MS (and other autoimmune) processes?
If so, how might this be achieved? I know that several genetic disorders are currently being heavily researched by scientists investigating gene therapies… Might MS and other autoimmune diseases be thought of as some sort of genetic disorders if in fact they are linked to retroviral material in our DNA that has been “switched on” by viruses or other environmental factors?
I couldn’t agree with you more . my gut feeling is that something connected to a previous lung infection might be linked to ms.
The year previous to ms and being pregnant I got a massive lung infection that resulted in having asthma for four years . I got rid of the asthma but by then ms had been 3 years with me .
2 questions about EBV
1 in your opinion how long between having glandular fever and having MS symptoms? I had glandular fever and two years later problems with my vision and three years later problems with my hands. How long does ebv take to activate ms?
2 if an ebv vaccination was offered would this be offered to people who had already had glandular fever?what happens to the virus after you have symptoms and get better?
questions about EBV
1 in your opinion how long between having glandular fever and having MS symptoms? I had glandular fever and two years later problems with my vision followed one year later by problems with my hands. How long does ebv take to activate ms?
2 if an ebv vaccination was offered would this be offered to people who had already had glandular fever?what happens to the virus after you have symptoms and get better?
“questions about EBV”
Google: last hope for progressive ms: ebv CD8+ Tcells Pender
ttps://soundcloud.com/bioanalysis-zone/nctalks-at-aan-2017-michael-pender-on-a-new-multiple-sclerosis-treatment
https://www.google.com/search?client=firefox-b-1-d&ei=P4IOXdmrDtaz0PEP85ii-Ag&q=pender+ms+ebv+CD8%2B&oq=pender+ms+ebv+CD8%2B&gs_l=psy-ab.12…0.0..1746315…0.0..0.0.0…….0……gws-wiz.QyQ74vlgZ9Q
My question is why is there such a push for immunosuppressant trials, even in progressive patients, when clearly B-cells and T-cells are treating nothing more than a downstream reaction?
Clearly immunosuppressants are working very minimally to stop progressive disease. Please show me clear evidence that even RRMS to SPMS is being inhibited. Immunosuppressants are nothing more than a band-aid and not addressing the real issue.
It is time to hand over the control of research from to genetics and virology to use antivirals or initiate removal of DNA sequence of these HERV affecting microglia and oligodendrocytes. If it is EBV memory B-cells in follicles of the brain are “awakening” these HERV then CNS penetrant antivirals or the primed CD8 killers of EBV controlled B-cells, not monoclonal antibodies that do not cross the BBB, are the answer.
I remember a similar horrific story in medicine when barbaric surgeries were performed on GI ulcer patients when in fact it was discovered by an Australian researcher to be a bacteria, Helicobacter pylori, causing the ulcers and easily treated with antibiotics and proton pump inhibitors. The journey with immunosuppressant agents in MS remind me of this.
“Please show me clear evidence that even RRMS to SPMS is being inhibited.”
Have seen studies on both sides…but we know 2 untreated people will differ in conversion so hard to give benefit credit to the drugs.
“The journey with immunosuppressant agents in MS remind me of this.”
Not to mention the $$$ cost…an incredible financial heist/scam…
S.Hauser brings this up….”Long-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious(hidden) disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS”
“Moreover, as relapses and focal white matter lesions are brought under excellent control by disease‐modifying therapies for RRMS, the effectiveness of these agents against silent progression is likely to represent a key determinant of their relative value.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518998/
Excellent comment.
“It is time to hand over the control of research from to genetics and virology”
Well here you go….Rajiv Khanna holds intellectual property for Pender’s therapy.
…Prof Khanna is an internationally recognized Translational Immunologist who has made major contributions in the development of cellular immunotherapies for the treatment of virus-associated cancers and infectious complications. He has also developed novel immune-based diagnostic tools which have been successfully commercialised and implemented in clinical settings. He is the founding Director of the QIMR Centre for Immunotherapy and Vaccine Development.
He has extensive expertise in immunotherapy clinical trials, cancer immunology and vaccine development. The major goals of his research group are to obtain a deeper understanding of the mechanisms by which human immune response to viruses and cancers may be generated, augmented and applied to control these diseases. Over the last two decades, his group has successfully translated his research towards the development of novel T cell-based immunotherapeutic strategies for the treatment of cancer patients and transplant recipients.
https://au.linkedin.com/in/rajiv-khanna-ab116825
Excellent informative posts. Thank you.
It sounds like MS research and treatment are on the brink of a much needed revolution.
“The evidence for EBV being the cause of MS is so overwhelming ”
Guess waht ?
I just learn that men are more prone to viral infections than women
How are you going to explain the 3 to 1 ratio in incidence of women over men in ms “epidemic”
For one thing, the genetic component could be X-chromosome related. And where is the evidence of men being more prone to viruses? Man flu maybe? 😉
“learn that men are more prone to viral infections than women”
Not the amount of infections…it’s how you respond to EBV…and how EBV responds to you.
https://www.msard-journal.com/article/S2211-0348(17)30118-9/fulltext
This paper dont explain pediactric ms
The variety and strength of
these studies indicate that EBV is directly involved in most MS cases.
However, the vast majority of EBV infections occur in childhood
(Balfour et al., 2013
), yet the onset of MS is much later, usually in
early adulthood
There are children with ms with 8 years
“There are children with ms with 8 years”
And some get it at 58 years…8..38…or 58 it’s still EBV.
Theory is some have more CD8+ to keep EBV controlled.
Yet the ms onset is very late
Aparently it isnt
“EBV simply wakes-up, or resurrects, these dormant viruses which then activate the immune system and trigger autoimmunity. This is why we are so keen to target HERVs with antivirals as a treatment strategy for MS. ”
Or hijack it to survive. We have more autoimmunes because we have a more evolved hepres species.
Herpes Virus and Tumors Evolved to Learn How to Manipulate the Same Ancient RNA
https://neurosciencenews.com/cancer-herpes-rna-10539/?fbclid=IwAR2vNpKzDzFts-3qDHFt8mxUBGqDf4zE_IWHfHjo4yi34flg1cooxtgGA0U
Head trauma…
“Those who had suffered a single concussion between the ages of 10 and 20 had a 22% higher rate of MS than those who had never had a concussion.
The rate of MS was more than doubled for those who had experienced more than one concussion.”
https://www.health.harvard.edu/blog/may-discovered-cause-multiple-sclerosis-ms-2017110312670
Well, NFL players suffer from Chronic Traumatic Encephalopathy but not MS… I wouldn’t count much on this theory
Well I had a bad concussion at 17 following a car accident and then had glandular fever at 20 then had my first episode of MS with vision problems at 22
Father was a heavy smoker and I was born in April which apparently is a common month for those with MS to have been born in
I guess I have the odds stacked against me
Will ProfG be tempted to be that super athlete again and go for the transplant that will make him Speedy Gonzalez or simply take propionate supository?…..Harvard turning Sh1 into Gold:-)
https://www.nature.com/articles/s41591-019-0485-4
Mice on treadmills to Marathon runners…or is it gum disease:-)