Microbiome is associated with MS


If you are interested you can have a read of this paper. I don’t comment much on microbiome (gut bacteria) stuff, because frankly I don’t understand it. Yep we are what we eat but which bacteria and how do they influence disease is complex. What are the pathways and are there any common componenents? Looking as a handful of papers their seem to be more options than “hot dinners” Maybe we need some guest posts on this from people in the know

Gut microbiome is associated with multiple sclerosis activity in children.Horton MK, McCauley K, Fadrosh D, Fujimura K, Graves J, Ness J, Wheeler Y, Gorman MP, Benson LA, Weinstock-Guttman B, Waldman A, Rodriguez M, Tillema JM, Krupp L, Belman A, Mar S, Rensel M, Chitnis T, Casper TC, Rose J, Hart J, Shao X, Tremlett H, Lynch SV, Barcellos LF, Waubant E; U.S. Network of Pediatric MS Centers.Ann Clin Transl Neurol. 2021 Aug 19. doi: 10.1002/acn3.51441.

Objective: To identify features of the gut microbiome associated with multiple sclerosis activity over time.

Methods: We used 16S ribosomal RNA sequencing from stool of 55 recently diagnosed pediatric-onset multiple sclerosis patients. Microbiome features included the abundance of individual microbes and networks identified from weighted genetic correlation network analyses.

Results: Participants were followed, on average, 2.1 years. Five microbes were nominally associated with all three disease activity outcomes after multiple testing correction. These included butyrate producers Odoribacter (relapse hazard ratio = 0.46, 95% confidence interval: 0.24, 0.88) and Butyricicoccus (relapse hazard ratio = 0.49, 95% confidence interval: 0.28, 0.88). Two networks of co-occurring gut microbes were significantly associated with a higher hazard of both MRI outcomes (gadolinium-enhancing lesion hazard ratios (95% confidence intervals) for Modules 32 and 33 were 1.29 (1.08, 1.54) and 1.42 (1.18, 1.71), respectively; T2 lesion hazard ratios (95% confidence intervals) for Modules 32 and 33 were 1.34 (1.15, 1.56) and 1.41 (1.21, 1.64), respectively). Metagenomic predictions of these networks demonstrated enrichment for amino acid biosynthesis pathways.

Interpretation: Both individual and networks of gut microbes were associated with longitudinal multiple sclerosis activity. Known functions and metagenomic predictions of these microbes suggest the important role of butyrate and amino acid biosynthesis pathways. This provides strong support for future development of personalized microbiome interventions to modify multiple sclerosis disease activity.

Galluzzo P et al. Comparison of the Intestinal Microbiome of Italian Patients with Multiple Sclerosis and Their Household Relatives. Life (Basel). 2021 Jun 26;11(7):620. 

In this study, we compared the gut microbiome in MS patients and their household healthy relatives sharing lifestyle and environmental factors…..We observed an increase in Ruminococcaceae, Christensenellaceae, Desulfovibrionaceae, Clostridiales, and Family XIII in MS patients, while Bacteroidaceae, Tannerellaceae, Veillonellaceae, and Burkholderiaceae were more abundant in healthy controls

Ling Z, Cheng Y, Yan X, Shao L, Liu X, Zhou D, Zhang L, Yu K, Zhao L. Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis. Front Immunol. 2020 Dec 16;11:590783.We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium, decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS 

Cox LM, Maghzi AH, Liu S, Tankou SK, Dhang FH, Willocq V, Song A, Wasén C, Tauhid S, Chu R, Anderson MC, De Jager PL, Polgar-Turcsanyi M, Healy BC, Glanz BI, Bakshi R, Chitnis T, Weiner HL. Gut Microbiome in Progressive Multiple Sclerosis. Ann Neurol. 2021 Jun;89(6):1195-1211.Microbiota β-diversity differed between MS patients and controls but did not differ between RRMS and progressive MS or differ based on disease-modifying therapies. Disease status had the greatest effect on the microbiome β-diversity, followed by body mass index, race, and sex. In both progressive MS and RRMS, we found increased Clostridium bolteae, Ruthenibacterium lactatiformans, and Akkermansia and decreased Blautia wexlerae, Dorea formicigenerans, and Erysipelotrichaceae CCMM. Unique to progressive MS, we found elevated Enterobacteriaceae and Clostridium g24 FCEY and decreased Blautia and Agathobaculum. Several Clostridium species were associated with higher EDSS and fatigue scores. Contrary to the view that elevated Akkermansia in MS has a detrimental role, we found that Akkermansia was linked to lower disability, suggesting a beneficial role. 

Eckman E, Laman JD, Fischer KF, Lopansri B, Martins TB, Hill HR, Kriesel JD. Spinal fluid IgG antibodies from patients with demyelinating diseases bind multiple sclerosis-associated bacteria. J Mol Med (Berl). 2021:1–13. A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD). The anti-microbial ELISA assays follow on prior human brain tissue RNA sequencing studies that established multiple sclerosis (MS) microbial candidates. Lysates included in the ELISA panel were derived from Akkermansia muciniphila, Atopobium vaginae, Bacteroides fragilis, Lactobacillus paracasei, Odoribacter splanchnicus, Pseudomonas aeruginosa, Cutibacterium (Propionibacterium) acnes, Fusobacterium necrophorum, Porphyromonas gingivalis, and Streptococcus mutans. CSF responses from patients with demyelinating diseases (DD, N = 14) were compared to those with other neurological diseases (OND, N = 8) and controls (N = 13). Commercial positive and negative control CSF specimens were run with each assay. ELISA index values were derived for each specimen against each of the 10 bacterial lysates. CSF reactivity was significantly higher in the DD group compared to the controls against Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Four of the 11 tested DD group subjects had elevated antibody indexes against at least one of the 10 bacterial species, suggesting intrathecal antibody production. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients. KEY MESSAGES: A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases, including multiple sclerosis and acute disseminated encephalomyelitis. CSF reactivity was significantly higher in the demyelination group compared to the controls against the bacteria Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Several of the demyelination subjects had elevated antibody indexes against at least one of the 10 antigens, suggesting at least limited intrathecal production of anti-bacterial antibodies. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients.

So what is common here to explain a common presentation of a condition across many parts of the World

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  • All I can say is amazing. Always knew that my MS symptoms were activated by certain foods. Thank you , I wait for more information.

  • I got my microbioom and a lot of other stuff checked out by Medivere (german lab)
    Why spend money on an gut ‘polaroid’, well because i wanted to know what was going on and just maybe it could lead to something in the future. So can someone please tell me what to eat now based on my bugs:

    Firmicutes** 62,522 % 50,0 – 58,0
    Euryarchaeota** 0,057 % < 0,03
    Tenericutes** 1,135 % 0,003 – 0,100
    Akkermansia muciniphila** 1,714 % 0,01 – 1,50
    Desulfovibrio spp.** 0,823 % < 0,1
    Oscillibacter spp.** 4,330 % < 0,02
    Alistipes spp.** 6,133 % 1,6 – 5,0
    Methanobacteria** 0,057 % < 0,002
    Methanobrevibacter smithii** 0,054 % < 0,002
    Pseudomonas spp.** 0,003 % < 0,001
    Alistipes spp.** 6,133 % 1,6 – 5,0
    Clostridium spp.** 7,096 % 1,0 – 2,3
    Clostridium difficile** 0,004 % 0,001
    Lactobacillus brevis** 0,000 % > 0,001
    Lactobacillus plantarum** 0,000 % > 0,001
    Lactobacillus paracasei** 0,000 % > 0,001
    Ruminococcus spp.** 2,693 % 4,9 – 8,1
    Eubacterium spp.** 0,232 % 0,3 – 2,3
    Faecalibacterium prausnitzii** 0,208 % 1,9 – 5,0
    Roseburia spp.** 0,054 % 0,5 – 2,4
    Ruminococcus spp.** 2,693 % 4,9 – 8,1
    Dorea spp.** 0,084 % 0,3 – 0,8
    Bifidobacterium spp.** 0,235 % 0,6 – 4,5

  • I’m certainly not one of those in the know. These types of observational studies run counter to my bias of a more reductionalist approach. (The complexity of all the different networks and populations of gut bacteria makes my head explode.) But I’m stuck by the focus of these papers on bacteria that could picked up by sequencing the 16S ribosome. This excludes of course fungi, viruses, mobile genetic elements and all sorts of other microbiota. Another thing that struck me from the first paper, “Gut microbiome is associated with multiple sclerosis activity in children,” was the prevalence of butyrate-producing bacteria. Butyrate is a strong lytic activator of EBV. So it begs the admittedly far-flung hypothesis that the gut microbiome may be influencing activation of EBV and the immune system that may induce MS pathology. I know this is a huge stretch, but something that should be further explored.

  • Surly gut bacteria plays a role in some way, around 70%. We’ve evolved to have to immune system located ther, for what reason? Who knows.

    But In some way there must be some communication

    • We have evolved an immune system in the gut….maybe because it is an easy place for infections to enter the body.

    • Any mucosal surfaces have a resident microbiome (mouth ,gut ,urogenital tract,nose etc)

      It make sense to have a lot more immune cells present if you have a lot more bacteria ,virus also present each is the case of the gut

      Remember 1 gram of feces as 1 000 000 000 bacteriophages and thats just one tiny part of your virome that live in your gut

  • As far as I am aware of there is supposedly a link between the variation in your food and your microbiome. While I am aware that it is quite hard to track what people are eating on a daily basis, there are data sets from economics and marketing called “Scanner Panel Data” (e.g., by Nielsen) where households scan their purchases (depending on the data set it is a more or less complete representation of their purchases in supermarkets) and the research obtains a granular view on their consumption. If one would combine this data with additional health and MS data, one could measure the effect of food diversity on disease progression.

    Maybe this is a nice collaboration between the health and the economics department of some university? 🙂

  • MD, I would respectfully ask that you find another less grab-em-by-the-throat way to highlight boxes than the rainbow of intense colors you’re using. A significant portion of men are seriously color blind. Also, I would suspect a significant portion of your readers have MS-related eye issues that are also not helped by those colors.

      • Yes, light blue is one of the better colors, if you must use them. However, I would point out – as a former IT person – that all elements of a web page should be chosen with enhancing or making easier the user experience, not because of the design preferences or aesthetic sense of the developers. (Sadly, this is not the case anymore) If the goal is to have people actually read your posts then thinking about how people actually read them rather than how you find them attractive, is key. I’m not sure why much color is required for stuff like this anyway. But if a post’s colors make my eyes start to bleed I know I won’t bother with trying to read it.

        Here’s an absolutely classic piece that I found several years ago when I wondered if I was losing my vision/getting old/going mad. Probably a bit of all three, but in of web readability, it actually wasn’t me. This article will change how you judge webpages from here on out I suspect.

        How The Web Became Unreadable

        • OK How do you want the copied text of the paper title and abstract to be distinguished from what I am saying?

  • Look at Alzheimer’s disease. Who would of thought Bactria found in the mouth (P. gingivalis) the bacteria that causes gingivitis is thought to play a role in the development of Alzheimer’s, and is found in the brain.

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