Gut time

G

Why don’t I bother reporting microbiome studies as the next great cure and why not report all the supportive (scientifically interesting) animal studies which give us “Cure of the week”.

Simple…the data seems to be something that is produced via the intestine and the effects are simply not good or consistent enough….for it to be ready for prime time.

This week Lactobacillus (gut bacteria) hit the news and in this weeks PeeNas we have

Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity. Montgomery et al. PNAS 2020; https://doi.org/10.1073/pnas.2002817117

Significance “Our results demonstrate a complex interplay between host genotype and gut microbiota in autoimmune disease, and identify a single species capable of modifying disease susceptibility in a genetically susceptible host. Our studies underscore the need to consider host genetics and baseline gut microbiota composition in autoimmunity”.

We identified specific gut bacteria and their metabolic functions associated with EAE susceptibility, implicating short-chain fatty acid metabolism as a key element.

“Manipulation of the gut microbiome by transplantation and cohousing demonstrated that transfer of these microbiomes into genetically identical hosts was sufficient to modulate EAE susceptibility and systemic metabolite profiles. Parallel bioinformatic approaches identified Lactobacillus reuteri as a commensal species unexpectedly associated with exacerbation of EAE in a genetically susceptible host, which was functionally confirmed by bacterial isolation and commensal colonization studies”.

These results reveal complex interactions between host genetics and gut microbiota modulating susceptibility to CNS autoimmunity, providing insights into microbiome-directed strategies aimed at lowering the risk for autoimmune disease and underscoring the need to consider host genetics and baseline gut microbiome composition.

Therefore you start to ask, is it a practical approach?.

What does Lactobacillus reuteri do in other peoples hands? Well it makes it worst (Miyauchi et al. 2020)… no I mean better (He et al. 2019)…Hence a potential problem

Miyauchi et al. (2020) Gut microorganisms act together to exacerbate inflammation in spinal cords.Nature. doi: 10.1038/s41586-020-2634-9

It says “No statistical methods were used to predetermine sample size. The experiments were not randomized and investigators were not blinded to allocation during experiments and outcome assessment”

So maybe a bias experiments but it says the bacteria make T cells reactive to myelin

“Here we show that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4+ T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG”. 

Lactobacillus is bad news, but other studies says Lactobacillus is good news

He B, Hoang TK, Tian X, Taylor CM, Blanchard E, Luo M, Bhattacharjee MB, Freeborn J, Park S, Couturier J, Lindsey JW, Tran DQ, Rhoads JM, Liu Y. Lactobacillus reuteri Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Mice by Modulating Gut Microbiota. Front Immunol. 2019 Mar 7;10:385.

“The gut microbiome plays an important role in immune function and has been implicated in multiple sclerosis (MS). However, how and if the modulation of microbiota can prevent or treat MS remain largely unknown. In this study, we showed that probiotic Lactobacillus reuteri DSM 17938 (L. reuteri) ameliorated the development of murine experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, a model which is primarily mediated by TH17 and TH1 cells. We discovered that L. reuteri treatment reduced TH1/TH17 cells and their associated cytokines IFN-γ/IL-17 in EAE mice. We also showed that the loss of diversity of gut microbiota induced by EAE was largely restored by L. reuteri treatment. Taxonomy-based analysis of gut microbiota showed that three “beneficial” genera Bifidobacterium, Prevotella, and Lactobacillus were negatively correlated with EAE clinical severity, whereas the genera Anaeroplasma, Rikenellaceae, and Clostridium were positively correlated with disease severity. Notably, L. reuteri treatment coordinately altered the relative abundance of these EAE-associated taxa. In conclusion, probiotic L. reuteri changed gut microbiota to modulate immune responses in EAE, making it a novel candidate in future studies to modify the severity of MS.”

So look at the data. Ask “Is it a “Cure of the Week”? The simple answer is No.

The effect on the disease is marginal, so don’t expect the disease to go away.

If you want to take probiotics, take pro biotics but don’t expect earth-shattering changes. The work is too early to be prime time…yet clinical trials are already full steam ahead and as you can imagine I think if we are lucky we will see a small influence….Enough for a platform presentation at ECTRIMS 202X, but not challenging pharma for the top spot in disease control.

I could be wrong and you may get

So when you pop down to the local health spa or pop-up one-stop-shop to get your faecal transplant for a few thousand…just see it as a bit of pampering and RnR…that you are paying for. Then you won’t be disappointed if the results don’t go the way you are led to believe by dubious docs, the media and scientific hype.

When it is ready for prime time, I will be there chocolate shake in hand.

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MouseDoctor

10 comments

  • Isn’t this a re-run for the diet argument in MS, i.e. that by eating well, general health is improved, co-morbidities are less likely and so the body withstands the MS better? From what I’ve read, the best diet is one which incorporates improving one’s gut health, so it’s not necessary to supplement with probiotics etc. It’s the Mediterranean diet +.

  • Symptoms and PIRA mitigation:
    So long as Bart’s doesn’t say that individual supplements are definitely a bad thing for MS/general health or that they show no evidence at all of potential benefit then why not work to the approach: ‘this may help so it’s worth it’
    Lipoic Acid and the good quality study there being a case in point.
    The MS version of ‘prevention is better than cure’ if you like.
    There’s no cure anywhere in sight on the horizon so it’s a focus on maximising being as well as possible for as long as possible – DMTs for sure + diet, exercise, mental stimulation, social interaction, and yes supplements.

      • I was fortunate enough to receive treatment with Alemtuzumab (at point of being treatment naive) since which I’ve been NEDA for the past three years. This was after being diagnosed with late onset highly active MS (I’m 56)

        I’m a good weight with good BMI and have no comorbidities. Although I’m no longer able to run at all or walk very far I am able to exercise both at home and at the gym.

        I am taking the approach of ‘if it might help’ so I try and eat a mainly healthy diet and use IF : consuming calories between 1pm and 8pm and rarely drink alcohol (fortunately I really dislike sugary drinks)

        I don’t work and don’t have any children living at home. Therefore have lots of time for self care – Mindfulness, yoga, gardening etc.

        I mentioned all this because obviously we’re all different and it’s sensible, isn’t it, to be sure of being safe to take supplements.

        Also think that maybe it’s important to acknowledge I can afford everything I buy – our circumstances as PwMS will, of course, vary greatly!
        Ditto that I pay to see a neuro physio once every six months.

        I’ve googled side effects/safety profiles for the supplements I’ve chosen to take and it’s shocking how little evidence there is – lots of references along the lines of ‘presumed to be safe’

        The supplements I take are:
        Lipoic Acid. *
        Nano curcumin. *
        CDP Choline.
        Vit D3.
        Keltican Forte.
        Magnesium L-Threonate.
        N-Acetyl Glucosamine.*
        5-LOX Inhibitor with ApresFlex*
        D- Mannose & Cranberry Extract*

        * Luis is definitely the one to provide the relevant info on the studies of Lipoic Acid.
        * Post here on Bart’s about Curcumin.
        * I’m taking the NAG and 5-LOX not solely for the MS but because arthritis is a real problem in my family.
        * ProfG recommended the D-M and Cranberry for ITUs (I’m hoping to achieve prevention of)

        I take the probiotics VSL#3 and Viviomixx on alternate days.

        None of this is a panacea – I still experience lots of fatigue, some cog fog and lots of physical pain, alongside my EDSS level 2 degree of disability. But I am buoyed most of the time by a sense of feeling I’m being proactive!

        If you can afford it I definitely recommend seeing a neuro physio.
        I was stumbling around with foot drop and using a walking stick when I first met mine (before having Alem) and the exercises she provided has meant that in the last four years I’ve not needed the stick and can do 3km on a treadmill.
        Professionals like this, if you use their input on a daily basis, are worth their weight in gold!

        • Thank you, Fi, for the thorough response. I see that lipoic acid featured in Prof G’s recent, somewhat infamous advice to Sid. Maybe I can I find past posts from Luis re same. And I’ll take a look at the others you list. Thanks again.

    • “why not work to the approach: ‘this may help so it’s worth it”

      Because if it does not you have destroyed brain/spinal cord way beyond current medical reality.

      “There are’s no cure anywhere in sight on the horizon so it’s a focus on maximising being”

      HSCT/Alemtuz are not cures because they don’t work for everyone..but people who were progressing have gone 20 years w/no progression on them. IRT vs. DMT is the difference.

    • Luis, whilst were talking about supplements – can I you about lipoic acid please? I know you’re an advocate and that you’re response will be evidence based but I was confused about dosage and whether it is R-version that was used in the trials? Thanks

  • You are always one step ahead of the field MD! Article posted today about the Impact of Gut Microbiota in MS: https://multiplesclerosisnewstoday.com/news-posts/2020/10/22/impact-gut-microbiota-in-ms-more-complex-than-previously-thought-study-shows/

    The article states, “These findings highlight the complex interactions between gut microbiota and genetic background in driving MS susceptibility”.

    This article further support for using genetics to individualize pwms treatment plans. The more we push and talk about incorporating genetics into MS patient care, maybe we can get some traction/interest.

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