Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet

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Keith

The Gut Club
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This is posted in the Gut-Brain Epilepsy Project thread, but I don't want it to be missed, so starting a separate thread here in The Kitchen.

#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
 
The study was done with mice. There is more that researchers need to do before saying the same is the case in humans.
 
In many epileptic patients, anticonvulsant drugs either fail adequately to control seizures or they cause serious side effects. An important adjunct to pharmacologic therapy is the ketogenic diet, which often improves seizure control, even in patients who respond poorly to medications. The mechanisms that explain the therapeutic effect are incompletely understood. Evidence points to an effect on brain handling of amino acids, especially glutamic acid, the major excitatory neurotransmitter of the central nervous system. The diet may limit the availability of oxaloacetate to the aspartate aminotransferase reaction, an important route of brain glutamate handling. As a result, more glutamate becomes accessible to the glutamate decarboxylase reaction to yield gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter and an important antiseizure agent. In addition, the ketogenic diet appears to favor the synthesis of glutamine, an essential precursor to GABA. This occurs both because ketone body carbon is metabolized to glutamine and because in ketosis there is increased consumption of acetate, which astrocytes in the brain quickly convert to glutamine. The ketogenic diet also may facilitate mechanisms by which the brain exports to blood compounds such as glutamine and alanine, in the process favoring the removal of glutamate carbon and nitrogen.

Keywords: ketosis, brain amino acid metabolism, epilepsy, anticonvulsant therapy

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237068/

Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or serum glutamic oxaloacetic transaminase (SGOT), is a pyridoxal phosphate (PLP)-dependent transaminase enzyme

AST relies on PLP (Vitamin B6) as a cofactor to transfer the amino group from aspartate or glutamate to the corresponding ketoacid.

https://en.wikipedia.org/wiki/Aspartate_transaminase

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to GABA and CO2. GAD uses PLP as a cofactor.

https://en.wikipedia.org/wiki/Glutamate_decarboxylase

Also see:

https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-10-273

I have been prescribed vitamin B6 for over 47 years and have used a multi B complex tablet since 1990 to treat a rare condition known as PNPO Deficiency.


**DO NOT ALTER ANY MEDICATION WITHOUT YOUR DOCTOR'S CONSENT**
 
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Another new paper:
"KD also increased the relative abundance of putatively beneficial gut microbiota (Akkermansia muciniphila and Lactobacillus), and reduced that of putatively pro-inflammatory taxa (Desulfovibrio and Turicibacter)."
Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice
https://www.nature.com/articles/s41598-018-25190-5

Andrew, gut microbiota are known to regulate amino acid levels. They also are responsible for making and breaking B-vitamins including B6.

If anyone is interested in doing a stool test to know your microbial balance, please see here:
http://thegutclub.org/ubiome-stool-testing/

jen, the mouse microbiome is similar to human as it is for dogs and pigs. This is why they are used to model humans. But there are differences, of course, and care should be taken. Regardless, we do know the ketogenic diet is effective in reducing seizures. Flora shift as main mechanism is gaining rapid acceptance. With this new insight, we can put greater focus on flora balance in ways other than the diet and improve the condition even more so. There is also some debate about the type of ketogenic diet and if simply low carb diets are enough. I believe the diet must be personalized which is why microbial DNA stool testing is important. Organic acid urine testing (OAT) is another important test to learn about microbial balance.

The point is we are all "walking compost heaps" and it is our responsibility to stay in balance.
 
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