Gut-Brain Epilepsy Project - Important Info

Keith

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#gutbrainepilepsyproject
New UCLA study:
"The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet"
Published: May 24, 2018
•Changes in the gut microbiota are required for the anti-seizure effects of the KD
•Specific KD-associated bacteria mediate and confer the anti-seizure effects of the KD
•KD microbiota regulate amino acid γ-glutamylation and hippocampal GABA/glutamate
Paper here:
https://www.cell.com/cell/fulltext/S0092-8674(18)30520-8

Article about the new paper:
https://www.livescience.com/62659-keto-diet-epilepsy-gut-bacteria.html
 

Keith

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Bernard

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From the Bloom Science page:
... Based on the bacterial strains identified by Hsiao’s team, the company plans to develop a product that would be classified as a medical food, which would take a less stringent path for regulatory approval and lead to a designation that it is generally regarded as safe (GRAS). Colasin said Bloom also plans to pursue conventional regulatory approval as a Live Biotherapeutic Product for its proprietary strains of bacteria, leveraging the orphan drug pathway with the FDA.
Sounds like yogurt.
 

Keith

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Bernard, agreed, but with particular strains of microbiota along with a prebiotic to help feed them. The protocol should be personalized to include many dietary and other factors.

The new paper is revealing microbial mechanism behind KD in seizure disorder.
"A. muciniphila is capable of metabolizing components from the KD and CD diet to support P. merdae growth, and that this cooperative interaction reduces GGT activity. In turn, reductions in GGT activity in P. merdae promote A. muciniphila growth . . . KD alters the gut microbiota, promoting select microbial interactions that reduce bacterial gamma-glutamylation activity, decrease peripheral GG-amino acids, elevate bulk hippocampal GABA/glutamate ratios, and protect against seizures."
 

Jake

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If seizures are controlled would this be of any benefit to anyone?
 

Bernard

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If seizures are controlled would this be of any benefit to anyone?
I would think that if your seizures are controlled (100%) and your quality of life is good (ie. medication side effects are tolerable), you wouldn't want to change anything.

But if you don't have 100% control or side effects are intolerable, it might be worth investigating.
 

Keith

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June 2018:
Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet
"Compared with baseline, fecal microbial profiles showed lower alpha diversity after KD therapy and revealed significantly decreased abundance of Firmicutes and increased levels of Bacteroidetes. We also observed that Clostridiales, Ruminococcaceae, Rikenellaceae, Lachnospiraceae, and Alistipes were enriched in the non-responsive group."
https://www.sciencedirect.com/science/article/pii/S0920121118301578?via=ihub

#gutbrainepilepsyproject
 

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The last two citations both reference the same strains. Is that because they both tested patients on the Ketogenic diet and it's a diet specific result, or does it hold some correlation with epilepsy patients who are not on the ketogenic diet? Either way, I find the research fascinating.
 

Keith

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Another new take on KD related to flora shift (2019):
"Relative abundance of bifidobacteria as well as E. rectale and Dialister is significantly diminished during the intervention. An increase in relative abundance of E. coli is observed on KD."

"As relative abundance of health-promoting, fiber-consuming bacteria becomes less abundant during KD, we raise concern about the effects of the diet on the gut microbiota and overall health."
The ketogenic diet influences taxonomic and functional
composition of the gut microbiota in children with severe
epilepsy

https://www.nature.com/articles/s41...-0Ywc-nEp_6atIsmuMFkkY8NzCvtNwa6-IVchCqgzW5NQ
 

Bernard

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Saw this today and thought about Keith...

Researchers at UPMC Hillman Cancer Center and the National Cancer Institute (NCI) demonstrate that changing the gut microbiome can transform patients with advanced melanoma who never responded to immunotherapy--which has a failure rate of 40% for this type of cancer--into patients who do.

The results of this proof-of-principle phase II clinical trial were published online today in Science. In this study, a team of researchers from UPMC Hillman administered fecal microbiota transplants (FMT) and anti-PD-1 immunotherapy to melanoma patients who had failed all available therapies, including anti-PD-1, and then tracked clinical and immunological outcomes. Collaborators at NCI analyzed microbiome samples from these patients to understand why FMT seems to boost their response to immunotherapy.

"FMT is just a means to an end," said study co-lead author Diwakar Davar, M.D., a medical oncologist and member of the Cancer Immunology and Immunotherapy Program (CIIP) at UPMC Hillman and assistant professor of medicine at the University of Pittsburgh School of Medicine. "We know the composition of the intestinal microbiome--gut bacteria--can change the likelihood of responding to immunotherapy. But what are 'good' bacteria? There are about 100 trillion gut bacteria, and 200 times more bacterial genes in an individual's microbiome than in all of their cells put together."

Fecal transplant offers a way to capture a wide array of candidate microbes, testing trillions at once, to see whether having the "good" bacteria on board could make more people sensitive to PD-1 inhibitors. This study is among the first to test that idea in humans.

Davar and colleagues collected fecal samples from patients who responded extraordinarily well to anti-PD-1 immunotherapy and tested for infectious pathogens before giving the samples, through colonoscopy, to advanced melanoma patients who had never previously responded to immunotherapy. The patients were then given the anti-PD-1 drug pembrolizumab. And it worked.
...
 

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