Dysbiosis

D

Barts-MS rose-tinted-odometer: ★★★ (a lilac rose-tinted Sunday; and why not! #C8A2C8)

Dysbiosis refers to abnormalities in the human microbiome that affect disease and life outcomes. In the context of MS, it is claimed that changes in the gut microbiome may not only increase your risk of getting MS but act as a proinflammatory signal to drive MS disease activity and reduce remyelination and recovery. The corollary is that manipulation of your microbiome with antibiotics, faecal transplantation, probiotics and diet can be used to treat MS. Do you agree? 

My problem with the field of dysbiosis is how to interpret the data. Many of the hypotheses and claims being explored are plausible, but the lack of vigour and the application of causation theory in regard to some of the claims being made is worrying. More worrying is that some quacks have already jumped on the bandwagon and have started offering faecal transplants and probiotics to treat MS.

There is little doubt that the metagenome, i.e. our genomes and the genomes of the microorganisms that inhabit our bodies, is what life is. For example, without certain bacteria in our gut, we wouldn’t be able to eat certain foodstuffs. The most quoted example is the bacteria Bacteroides plebeius that allows humans to eat and breakdown seaweed; this bacteria is found more commonly in the gut of seaweed eating populations such as the Japanese. 

Trying to find the gut bacterium that causes MS or increase the chances of getting MS will be like seeking a needle in ten thousand haystacks. I have been thinking about how we tackle this problem. One way may be to look at populations that had low  incidence of MS and then to follow the changes in the gut microbiota longitudinally and see if something shows up in those who develop MS. The problem with this approach is the resources, the time required and the sheer size of the study required. 

What is clear is that your microbiome is very plastic and can be changed relatively easily by manipulating your diet; going from a high fibre diet to a low fibre diet or from a high carbohydrate diet to a ketogenic diet changes your microbiome within days. This is very relevant to managing some diseases, for example, ketogenic diets and their presumed effect on the microbiome increases the response rate of some cancers to certain chemotherapy regimens. The question is the metabolic hacking of ketosis or the effect of the diet on the microbiome that is responsible for the treatment effect? I suspect it is both. There is also very compelling data emerging that ketogenic diets are anti-inflammatory, which in addition to their neuroprotective effects, explains why they are being studied in MS and widely adopted by segments of the MS community. Are their other diets with as a compelling scientific rationale? Not to the best of my current knowledge.

In the context of the above, you may be interested in the animal (EAE) study below which shows a small therapeutic effect of the administration of Clostridia, a bacterium that may be beneficial in MS, as a treatment in mice induced to have experimental allergic encephalomyelitis or EAE. The treatment effect is quite modest; I doubt MD would be impressed with the size of the effect. However, the authors conclude “… gut dysbiosis in MS patients could be partially rebalanced by these commensal bacteria and their immunoregulatory properties could have a beneficial effect on MS clinical course”. Really?

Figure from Neurotherapeutics.

The question I have for you is how many of you are using probiotic supplements, diet, etc. to specifically change your microbiomes? How have you heard about these treatments and have you noticed any impact on your MS or MS-related symptoms? 

Calvo-Barreiro et al. Selected Clostridia Strains from The Human Microbiota and their Metabolite, Butyrate, Improve Experimental Autoimmune Encephalomyelitis. Neurotherapeutics (2021); Published: 07 April 2021.

Gut microbiome studies in multiple sclerosis (MS) patients are unravelling some consistent but modest patterns of gut dysbiosis. Among these, a significant decrease of Clostridia cluster IV and XIVa has been reported. In the present study, we investigated the therapeutic effect of a previously selected mixture of human gut-derived 17 Clostridia strains, which belong to Clostridia clusters IV, XIVa, and XVIII, on the clinical outcome of experimental autoimmune encephalomyelitis (EAE). The observed clinical improvement was related to lower demyelination and astrocyte reactivity as well as a tendency to lower microglia reactivity/infiltrating macrophages and axonal damage in the central nervous system (CNS), and to an enhanced immunoregulatory response of regulatory T cells in the periphery. Transcriptome studies also highlighted increased antiinflammatory responses related to interferon beta in the periphery and lower immune responses in the CNS. Since Clostridia-treated mice were found to present higher levels of the immunomodulatory short-chain fatty acid (SCFA) butyrate in the serum, we studied if this clinical effect could be reproduced by butyrate administration alone. Further EAE experiments proved its preventive but slight therapeutic impact on CNS autoimmunity. Thus, this smaller therapeutic effect highlighted that the Clostridia-induced clinical effect was not exclusively related to the SCFA and could not be reproduced by butyrate administration alone. Although it is still unknown if these Clostridia strains will have the same effect on MS patients, gut dysbiosis in MS patients could be partially rebalanced by these commensal bacteria and their immunoregulatory properties could have a beneficial effect on MS clinical course.

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. 

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

38 comments

  • How does the gut microbiome hypothesis fit with EBV, Vit D, gender difference, B cell involvement…. I follow Keto to keep a healthy weight, which in turn helps with exercise, less stress on joints etc., but am not convinced that changing the microbiome will have a major impact on established MS. EBV vaccine for prevention and anti-plasma cell therapy to try and slow progression look better bets that faffing around with poo!

    • ” but am not convinced that changing the microbiome will have a major impact on established MS. ”

      No..of course not..which is why these posts are incredibly reckless..irresponsible…and dangerous.

      People are convinced their diet has cured their ms just because they aren’t in a wheelchair.
      They burn up their neurological reserve and in 10-20 years hit spms and get to experience
      progressive ms.

      • Re: “which is why these posts are incredibly reckless..irresponsible…and dangerous.”

        Did you actually read the post? I am questioning the whole concept of dysbiosis as a theory and calling the HCPs offering treatments to treat dysbiosis ‘quacks’.

      • please take a look at this or you may contact with dr wahl. i really dot know how she could do this but i think it worth trying when one has a rouge immune system . does it work for all or not ? nobody knows . but you may find a complementary therapeutic strategy .

      • Have you read the book of terry Wahl? The physician with spms and a wheelchair risk g up from the wheelchair when she started to be her own doctor? Now climbing mountains, eating ketoglenic 2 meals a day….
        All the ms treatment adviced from her ms doctor just led her to spms and wheelchair.

        • Again, allegedly………………………you can extrapolate way too far and to suggest pwMS ignore expert medical advice is not only dangerous, it is immoral and quite often seems to be linked to hucksters who have some “miracle” diet/supplement etc to hawk. We’ve seen just the same thing with anti-vaxxer advice and COVID.

          “The diet promoted by Wahls to treat MS is a modified paleo diet, relying primarily on grass-fed meat, fish, leafy vegetables, roots, nuts, and fruit and restricting dairy products, eggs, grains, legumes, nightshade (solanaceous) vegetables, starches and sugar. Wahls has claimed that the diet alleviated the symptoms of her own multiple sclerosis.
          Wahls’ promotion of her diet and lifestyle regimen as an important strategy for managing MS-related symptoms as well as other disorders has been criticized for relying too much on anecdotal evidence, for failing to initiate adequate research to verify the claims, and for Wahls’ perceived conflicts of interest (selling numerous products and educational materials related to her protocol). A 2020 Cochrane review found no research supporting efficacy or effectiveness of diet or vitamin supplementation for treatment of MS.
          Clinical neurologist Steven Novella has commented that Wahls “paint[s] a picture of reality that is at drastic odds with the evidence” and elevates “nutrition to a magical stature that is not based on a lick of published evidence.”

  • I follow a high fiber diet mainly to combat constipation which in turn has a positive impact on my MS. I did try strict Keto for 6 weeks but felt terrible. The Keto flu lasted the whole time and the lack of fiber played havoc with my digestive system, the food was boring, i gained weight and I noticed no benefits. However, if the evidence is that strong, I may try again for longer and just invest in some good ibuprofen and laxatives.

    • Yep, ketogenic diets are very hard to stick to and not suitable for everyone. I actually think intermittent ketosis is all that is required to derive the benefits. I base this on principles of evolutionary medicine; there is little doubt that our ancestors ate carbohydrates, but they did cycle through feasts and famines and hence have the biochemical resilience to cope with both extremes.

      • Would be interested in details how you envision intermittent keto? What length of windows are you proposing?

        I can’t help but wonder if there is a link to Longo’s fasting mimicking diet which sounds promising in many ways – I presume that would put you in ketosis, too but obviously also works on protein (re)synthesis and possibly other, less obvious pathways?

  • After you, my dear (murine) Alphonse.

    This is very interesting, but it seems to me we are a long way from being able to introduce specific bugs with any expectation that they will act simply and/or as we intend them to. People’s gut microbe populations are hilariously various, and working out the potential mutual interactions in any single person at any single moment in time (let alone over a longer period) would surely puzzle any super-computer. Trying to figure out what an average healthy gut microbiome looks like or, indeed, whether that is even a meaningful concept, is going to be hard enough, and we’re not there yet. Fascinating stuff, though.

    • I have seen studies that say ms patient gut bacteria is as a groups different from Healthy people gut bacteria. Autoimmune diseases are more common in our part of the world and with western way of living. Aotoimmune diseases increase in our part of the world.
      If you compare our gut bacteria family with «nature nativ trives in ex Amazonas» our food gives us half the diversity og gut bscterus than theirs cause of fastfood and semifastfood. Coocked. Fried. Salt. Sugard. Little fibers. Little raw food etc etc

  • Been trying probiotics on and off for years, never really noticed a difference.

    Might be the product in question, who knows.

  • I am in a bile acid study at Johns Hopkins and receiving either TUDCA or placebo. The study is being conducted because it was determined through research that people with MS have low levels of bile acid. And such acid is neuro protective. Short study —four months. We will see. Ever hopeful.

  • I tried an extremely strict ketogenic diet (In a proof-of-concept study, we supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, we observed a significant and sustained increase of functionally competent regulatory T (Treg) cells, whereas Th1 and Th17 cells decreased significantly. Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake. Functional microbiome analysis revealed increased expression of Treg-cell-inducing genes in the intestine after PA intake. Furthermore, PA normalized Treg cell mitochondrial function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.

    I find it promising that they did this in people who were also on a DMT and still saw benefits to brain atrophy and disability progression. The problem with replicating this at home is that the only sources of sodium propionate I can find are bulk food-grade powder (which tastes absolutely vile) and compounding pharmacies which require a doctor’s prescription to give me pills.

    • It’s a hassle, but there are multiple way to encapsulate powders at home… Is there a write-up of the study available? Actual results on keto for pwms are rather elusive.

      • The article title is “Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism,” published in Cell in 2020. I somehow messed up the formatting of my previous post, all I meant to say about keto was that I had tried a very strict version of it for three months and noticed nothing one way or the other so I stopped.

    • “Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake.”

      Reduced brain atrophy means you are still having abnormal brain atrophy…this is not good.,
      Better to do hsct as many after 2 years get down to normal brain atrophy rate of .22

  • https://medicalxpress.com/news/2021-06-mind-diet-brain-people-multiple.html

    Latest that I’ve picked up about diet.
    Interesting to see the positive outcome to consumption of full fat dairy.

    Since reading about two specific probiotics of potential benefit in MS – Vivomixx and VSL#3 I’ve been taking them alternate days now for about a year. I don’t know if there’s a direct correlation but I’ve noticed my fatigue levels have decreased significantly. I also think there’s a lower level of cog fog.

    I also do 16/8 IF and eat a largely Mediterranean style diet but most definitely laced with chocolate and biscuits, some crisps and a couple of take always per month.

  • How about a fecal transplant from a healthy close relative (so the genetics are similar) who doesn’t have MS?

    Compare the gut microbiome before to see if there are any differences.

    Can’t be to much to lose.

  • I have had “benign m.s.” for 30 years. I am now 57 and am declining in energy, strength, mood. But am fairly fine.
    At age 40 I had to remove wheat from my diet and any alfalfa based products…it caused extreme histamine levels (measured) and I could barely walk or move. Removed from my diet I got better right away and remain very careful with wheat and alfalfa. .

    • “I have had “benign m.s.” for 30 years.”

      Just because you were benign for 30 years…doesn’t mean it can continue for 30 more.
      Progression is age related. People can have more progression in 3 months than what they had in last couple decades. Why you should consider alemtuzumab and hsct…as they could
      really halt any progression in the future.

      This article is one explanation for why you were benign 30 years:
      It is most likely not wheat/alfalfa.

      “Lower numbers of CD8+ T cells in females might contribute to the higher frequency of autoimmune diseases in females than males. Because the number of CD8+ T cells normally declines with increasing age, particularly through childhood [72], but also through adulthood [62, 70, 73], the primary CD8+ T cell deficiency will be aggravated as each person ages, as occurs in patients with MS [74]”

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270541/

  • Have tried but adding probiotics hurts my belly. Eat a very healthy diet otherwise and at a very healthy weight with no gut issues so nutritionist consult in agreement changes may harm more than help in this case

  • Dear Prof G,
    I tend to do on most days intermittent fasting (8:16), I try to avoid omega 6 intake as much as possible (I follow the diet by the German neurologist Olaf Hebener, who claims to have had some success with a VERY low omega 6 diet (below 2000 mg of omega 6/ Linoleic acid per day) with supplements of omega 3 and propionic acid (1000 mg/day). Otherwise I try to eat fermented products like Kimchi, Sauerkraut, self-made sourdough bread, water kefir and kombucha. Ah, and on top lots of different coloured veggies/fruits and once every three months I take for 6 weeks probiotics). I am okay, we will see the long term effects. (M, 32, dx in 2012, since then on rebif).

    Best regards and wishing you good recovery from your accident

    • You seriously need to find a new neurologist and get off rebif as soon as possible… Diet won’t do shit if you’re not on a highly effective dmt.

  • I feel my diet and lifestyle interventions are vital to the stability of my PPMS, which I (must) manage without medications.

    But I’m not going to waste time describing what I eat/don’t eat as I’ll be ignored or considered delusional.

    I have a crime novel to read.

    • You do not need to manage without medications, you should be on ocrelizumab at the very least… It will give you a decade longer of preserved upper limb function and seven additional years free of a wheelchair.

  • “have you noticed any impact on your MS or MS-related symptoms?”
    I suspect there may be more long-term benefits that are related in slowing down disease progression, rather than positively affecting existing symptoms. That’s not something you can ‘notice’ as an individual.

  • I have read the story of physician terry Wahl that changed her microbiota and her lectures are called «mind my mitocondria» . She was working few days a week and from a wheelchair – failed in all the treatments suggested by ms phycisians – took her destiny in her own hands, read a lot about ex microbiota and started change. It took her 2 tears from rising from the wheelchair to climbing mountains and she felles well today.

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