Gut instinct, the gut microbial changes in MS

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It’s probably not the first time that you’ve heard about gut microbes and MS. Particularly, the role that they may play in the development and regulation of MS.

Almost every study published in the literature has demonstrated differences in the gut microbiome in MS patients vs. healthy controls with the possibility that interventions on diet and the use of probiotics may have a favorable outcome.

This latest article on the topic published in Science Advances focuses on the finding that isoflavone-metabolizing bacteria are depleted in the gut of MS patients. Isoflavones are almost exclusively produced by the bean family, for example soya, and may have anti-inflammatory and anti-oxidant properties that may limit disease activity. In a mouse experimental model (EAE), investigators found that mice fed with isoflavones had suppression of their disease, with a reduction in CD4+ T cell infiltration into the CNS. Also, the gut micobiota fed with isoflavones paralleled that of healthy individuals, whereas those fed with an isoflavon-free diet were similar to those found in MS patients (see figure below). In essence the diversity of bacteria in each mouse (called the alpha diversity) was reduced in those on an isoflavone-free diet compared to an isoflavone diet suggesting that an isoflavone diet increases the species richness of the microbiome. Together these may help lower inflammatory triggers.

https://advances.sciencemag.org/content/advances/7/28/eabd4595/F4.large.jpg
Figure: An isoflavone and isoflavone-free diet alter the gut microbiome.(A) Schematic of experimental design. Four- to six-week-old female mice were placed on the indicated diet for 6 weeks followed by fecal collection, bacterial DNA isolation, and 16S sequencing analysis. (B) Chao index (t test, P = 0.023655) and PCoA (permutational ANOVA, P < 0.001) plots from mice on an isoflavone or isoflavone-free diet. Each dot represents a single mouse. Isoflavone free, n = 10 mice, two cages. Isoflavone, n = 13 mice, three cages. Values are from one independent representative experiment (C). Abundance values of the P. distasonis (t test, P = 8.8102 × 10−4; FDR (false discovery rate) = 0.0039646), Adlercreutzia (t test, P = 0.014204; FDR = 0.041794), and A. muciniphila (t test, P = 2.846 × 10−4; FDR = 0.0025614) as identified by sequencing analysis in (B), in mice on an isoflavone or isoflavone-free diet. (D) Levels of Adlercreutzia equolifaciens and P. distasonis in fecal samples, measured by qPCR using species-specific primers, from mice after 6 weeks on the indicated diet. P value was determined using Student’s t test; ****P < 0.0001. Higher CT values indicate lower levels of DNA whereas lower CT values indicate higher levels of DNA.

Abstract

Sci Adv. 2021 Jul 9;7(28):eabd4595. doi: 10.1126/sciadv.abd4595. Print 2021 Jul.

Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis

Samantha N JensenNicole M Cady Shailesh K Shahi Stephanie R Peterson Arnav Gupta Katherine N Gibson-Corley  Ashutosh K Mangalam 

The gut microbiota is a potential environmental factor that influences the development of multiple sclerosis (MS). We and others have demonstrated that patients with MS and healthy individuals have distinct gut microbiomes. However, the pathogenic relevance of these differences remains unclear. Previously, we showed that bacteria that metabolize isoflavones are less abundant in patients with MS, suggesting that isoflavone-metabolizing bacteria might provide protection against MS. Here, using a mouse model of MS, we report that an isoflavone diet provides protection against disease, which is dependent on the presence of isoflavone-metabolizing bacteria and their metabolite equol. Notably, the composition of the gut microbiome in mice fed an isoflavone diet exhibited parallels to healthy human donors, whereas the composition in those fed an isoflavone-free diet exhibited parallels to patients with MS. Collectively, our study provides evidence that dietary-induced gut microbial changes alleviate disease severity and may contribute to MS pathogenesis.

About the author

Neuro Doc Gnanapavan

18 comments

  • But does anyone really think that eating more beans is going to modify MS in any meaningful way?

    • Environmental factors such as diet and exercise are difficult to control for. I believe a healthier diet by large helps with a lot of conditions including MS. I certainly am susceptible to some dietary fads like anyone, but I know pretty quickly that some just make me feel unwell! A restricted diet is probably not very helpful for the body physiology as a whole and I wouldn’t recommend this. Adding Soya to my diet is not a hardship.

  • There is so much conflicting information re diet, Wahls protocol, auto immune protocol and paleo diets all say avoid legumes. I don’t personally avoid them, but I do note if I eat too many they are hard on my gut. I do believe there is a wrong link between gut and disease, I was diagnosed with a stomach ulcer at 7 year old, and years later when H.Pylori was discovered I was tested and had it too. It was never established which came first. Thanks I wonder how many pwms had gut issues pre dating there ma diagnosis

    • I think it’s safe to say that you would have had had Helicobacter pylori before the stomach ulcer. I think it’s also safe to say that as with eating a lot of legumes, these micrbiota studies can produce a lot of guff ;-).

    • I did some damage to my gut 50 years ago. As a child I used to climb onto a chair when mum wasn’t looking and eat the yummy orange flavoured aspirins. I used to get a lot of tummy aches and at some point a GP gave me chalky mint flavoured tablets for it. I can’t tolerate ibuprofen all this time later, I do wonder what damage I caused.

  • I see Dr. Michael Greger from nutritionfacts.org making another video and screaming: “Eat more beans! (with some broccoli that was precut about 45 minutes before cooking for the sulforaphane…)”

    Thanks for the study! I’ll get some chili…

  • Thank you for this post, I definitely feel that diet is crucial in managing MS. Above all, plenty of fibre. That’s what’s lacking more than anything else in the ‘western’ diet as I understand it.

  • ‘Previously, we showed that bacteria that metabolize isoflavones are less abundant in patients with MS, suggesting that isoflavone-metabolizing bacteria might provide protection against MS. Here, using a mouse model of MS, we report that an isoflavone diet provides protection against disease, which is dependent on the presence of isoflavone-metabolizing bacteria and their metabolite equol.’

    So adding isoflavones to our diet is only useful if we have the bacteria to metabolize it?

    • They’re there in the human gut microbiota, the relative proportions are variable in each individual. Or else you’ll struggle with Soya. As long as you’re not always on antibiotics your gut microbial make up shouldn’t change much. What happens in MS based on the work by this group is interesting to say the least.

      • I recently purchased Red Clover supplements (apparently contains isoflavones) for menopause purposes. I don’t think there is concrete evidence for efficacy but many women swear by it. Hopefully I’ll have the right bacteria to utilise it.

  • So if I have this right, an isoflavone-rich diet stimulates growth of isoflavone-metabolizing bacteria. After they’ve done `their work and produced more isoflavone metabolites, the MS gut more closely resembles a healthy human microbiome. Is the proposed preventative or restorative benefit conferred by the extra metabolites, the extra bacteria, some other process involving the additional beans – or are we not sure yet?

    Given the popularity of the keto diet, this is of more than passing interest. Beans, being rich in satisfying carbohydrates, are flora non grata in ketoland. Maybe Big Supplements has a capsule that delivers the isoflavones without the starch.

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