June 18, 2019

CURE Discovery: A Potential Link Between Gut Bacteria and Epilepsy

Key Points

  • Dr. Tore Eid’s CURE-funded research aims to understand how gut bacteria can impact seizure development, inflammation, and neurodegeneration.
  • The team found increased levels of certain amino acids, potentially made by gut bacteria, in the epileptic brain regions of individuals with focal epilepsies.
  • Short-term treatment with these amino acids reduced spontaneous seizures in a rat model of epilepsy, while a long-term treatment worsened seizure frequency.
  • Dr. Eid’s studies have the potential to develop epilepsy treatments such as dietary interventions and other safe manipulations of gut bacteria.
Deep Dive

CURE grantee, Dr. Tore Eid, and his team at Yale University, are conducting exciting research to understand how gut bacteria can influence the development and manifestation of seizures. This impactful work, funded by the Heldman-Kirshner family grant in honor of Alex Heldman, could lead to simpler and safer treatments for epilepsy.

ffb08cad-f59b-4586-b913-140d701d2c1f.pngOver 500 different types of bacteria live in our gut alone.1 This dense collection of bacteria, called gut microbiota, helps us digest food, provides important nutrients, builds immunity, and protects us from harmful pathogens. Disruptions to the gut microbiota play a role in many diseases including irritable bowel disease, colitis, and diabetes. There is also evidence that gut microbiota problems are linked to anxiety, depression, and autism spectrum disorders.2 How and whether these bacteria influence epilepsy development and progression is not very well studied. There is some evidence that the ketogenic diet, which is effective in reducing seizure frequency in a number of different epilepsies, may work by modifying the gut microbiota.3

To better understand the role gut bacteria may play in epilepsy, Dr. Eid and his team analyzed brain fluid samples from people with focal epilepsy. They found that epileptic brain regions had increased levels of certain amino acids called branched chain amino acids, which can be made by gut bacteria. Levels of some of these branched amino acids increased in the brain three hours before a spontaneous seizure occurred, while levels of other branched amino acids increased an hour before. This may indicate that there is a “fine-tuning” of these amino acids happening within the body which potentially impacts seizure occurrence.

Next, the team fed these branched chain amino acids to a rat model of epilepsy they developed. A short-term treatment decreased spontaneous seizures while a long-term treatment worsened seizure frequency and caused neuronal loss in an area of the brain called the hippocampus.4 These results provide evidence that molecules derived from gut bacteria can impact brain chemistry and seizure development.

The team is also interested in understanding how bacteria living in the gut can influence epilepsy development and progression in the brain, focusing on a large nerve called the vagus nerve. This nerve allows the brain and the gut to directly communicate with each other. Dr. Eid’s team has developed techniques to selectively stimulate or suppress signaling only through the afferent vagus nerve, which transmits messages from the gut to the brain, without affecting the efferent nerve, which transmits messages from the brain to the gut and other organs.

In future studies, Dr. Eid and his team will perform careful manipulations of gut bacteria in a rat model of epilepsy by feeding the animals specific types of bacteria. The types of bacteria the team plans to use make molecules which can influence brain chemistry and thus potentially affect seizures. The team will study the effect of this treatment along with afferent vagal nerve stimulation/suppression on seizure development, brain inflammation, and neuronal loss in the rats.

These studies have the potential to impact epilepsy treatment through safe manipulations of gut bacteria through, for example, dietary interventions, probiotics, or antibiotics.

1 Eckburg PB et.al. Diversity of the human intestinal microbial flora, Science. 2005 Jun 10;308(5728):1635-8
2 E.Y. Hsiao et.al Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders, Cell. 155 (2013) 1451-1463
3 Olson CA, Vuong HE et. al. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet, Cell. 2018 Jun 14;173(7):1728-1741.e13. doi: 10.1016/j.cell.2018.04.027
4 Gruenbaum SE, Dhaher R et. al., Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy, J Neurosurg Anesthesiol. 2019 Apr;31(2):247-256

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