Important Ketogenic Diet Benefit is Dependent on the Gut Microbiome

AUTHOR: DR. JASON BUSH

The benefits of the Ketogenic Diet, in which the vast majority of calories come from fat and carbohydrate sources are severely restricted, for the general population continue to be debated.  However, this restrictive diet can be an extremely effective tool in reducing epileptic seizures in children whose condition is not adequately controlled by seizure medications.  Prescribed by a physician and monitored by a dietician, the Ketogenic Diet typically cuts the number of seizures in half in over 50% of children and 10-15% of those children become seizure-free, according to the Epilepsy Foundation.

While effective, the mechanisms by which this nutrition-based therapy act are poorly understood.  But a new study suggests that the seizure-reducing effects of the Ketogenic Diet in individuals with epilepsy is mediated by the gut microbiome.

Surprising research from Dr. Elain Hsiao’s laboratory at the University of California, Los Angeles demonstrated that while the Ketogenic Diet was effective at reducing seizures in a mouse model of epilepsy, treating these mice with antibiotics made the seizures return.  Similarly, epileptic mice kept in germ-free conditions, in which the gut microbiome does not develop, still had seizures despite being fed the Ketogenic Diet.  Dr. Hsiao’s group found that two genera of bacteria – Akkermansia and Parabacteroides – were responsible for the effects of the Ketogenic Diet.  Reintroduction of either bacterium to mice with compromised microbiomes restored seizure control.  These experiments confirm a role for the gut microbiome in the therapeutic Ketogenic Diet for epileptic seizures.

But how do microbes in the gut affect seizures that occur in the brain?  Researchers found that the microbe-mediated effects of the Ketogenic Diet decreased levels of enzymes required to produce the excitatory neurotransmitter glutamate.  In turn, this increased the relative abundance of the inhibitory neurotransmitter GABA.  Taken together, these results show that the microbe-mediated effects of the Ketogenic Diet have a direct effect on neural activity, further strengthening support for the emerging concept of the ‘gut-brain’ axis.