Microbial Mediators

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Summary: UCLA researchers have identified a strategy to manipulate the gut microbiome to mimic the effects of a ketogenic diet, as a treatment for CNS disorders and metabolic diseases. Background: The low-carbohydrate, high-fat ketogenic diet (KD) is a known treatment for a variety of CNS diseases that are not well-treated with current therapeutics including refractory epilepsy and neurodegenerative indications as well as for metabolic syndrome. However the ketogenic diet is difficult to implement and maintain and has adverse side effects. For example, even with successful seizure reduction, epileptic patient retention on the KD is only an estimated twelve percent by the third year of therapy. Recently a UCLA team of researchers discovered that the ketogenic diet induces substantial changes in the gut microbiome. Via a comprehensive screen, the UCLA team then identified a set of two bacteria that are able to fully mimic the effect of a ketogenic diet in animal disease models when both bacteria are co-administered. Therapeutically, the concept is to replace the need for the ketogenic diet by enriching the microbiome with this set of two bacteria thereby mimicking the effects of a ketogenic diet. This approach may have significant benefits in terms of patient compliance, safety and efficacy. The initial proof of concept for this platform at UCLA is in refractory epilepsy. The efficacy of KD in this indication is supported by multiple retrospective and prospective studies, which estimate that ~30% of patients become seizure-free, and ~60% experience significant benefit. The UCLA team has demonstrated that mice that are colonized with the two bacteria or treated probiotically with the two bacteria exhibited protection against seizures. This was not seen with colonization with either bacterium alone. They then further validated the concept in a genetic mouse model of temporal lobe epilepsy. By EEG recording, mice treated with antibiotics to deplete the microbiome exhibit increases in frequency of tonic-clonic seizures. Conversely mice that were colonized with the two bacteria set exhibited restored seizure protection. Applications: The goal is to develop this two bacteria combination as a treatment platform that mimics the effect of the ketogenic diet. This has applications in a variety of CNS diseases that are not well-treated with current therapeutics including refractory epilepsy and neurodegenerative indications as well as metabolic syndrome. Advantages: Effective treatment for refractory epilepsy and an increasing number of other brain disordersAnti-seizure effects from altered microbes - See more at: https://techtransfer.universityofcalifornia.edu/NCD/27507.html#sthash.w9Zrck3G.dpuf