Scientists have long known that the ketogenic diet—a strict high-fat, low-carb regimen—is an effective treatment for reducing seizures in some people with epilepsy. Adhering to the diet is so difficult, however, that doctors consider it a treatment of last resort. And although many researchers have studied how the ketogenic diet affects the metabolism of neurotransmitters, no one has developed a therapy that encapsulates the diet’s antiseizure benefits.
That could soon change, however, thanks to a study published on May 24 by Elaine Hsiao and colleagues at the University of California, Los Angeles. Hsiao’s team discovered two kinds of bacteria in the gut microbiome that link the ketogenic diet to balancing excitatory and inhibitory neurotransmitters in the brain and to reducing seizures in two mouse models of epilepsy (Cell 2018, DOI: 10.1016/j.cell.2018.04.027).
Hsiao, who has studied the role of the microbiome in other conditions, including autism, is careful not to overhype the results. “Much more research needs to be done to determine whether these findings in mice translate to human epilepsy,” she says. Those human studies may come soon thanks to a new company called Bloom Science that Hsiao has helped found based on her research.
“We are hacking the ketogenic diet to identify microbes that have therapeutic potential for the treatment of epilepsy,” says Bloom CEO Tony Colasin.
The San Diego-based start-up isn’t announcing how much seed funding it raised, but Colasin plans to move fast and get a product on the market in a mere two to three years. That’s because Bloom will first develop a medical food based on the two kinds of bacteria identified in Hsiao’s study. Bloom also has plans to optimize the bacterial strains for specific kinds of epilepsy to develop a traditional approved drug.
The ketogenic diet was first developed almost 100 years ago, but its effect on the trillions of microbes residing in the gut has only been considered recently. When Hsiao’s team subjected epileptic mice to the diet, the rodents’ gut microbiomes changed significantly within days, and they experienced fewer seizures. When the researchers administered antibiotics to kill the gut microbes, the seizures returned.
The group identified two kinds of gut bacteria that flourish during ketogenic diets and appear to be important for reducing seizures: the Akkermansia muciniphila species and the Parabacteroides genus. In fact, transplanting these microbes into mice provided the seizure-reducing benefits without the grueling diet.
The way the bacteria help control seizures actually appears to be similar to the mechanism of many commercial antiepilepsy drugs. The microbes’ metabolism increases the ratio of inhibitory to excitatory neurotransmitters in the brain—specifically, higher levels of gamma-aminobutyric acid (GABA) relative to levels of glutamate.
GABA and glutamate are the brakes and the accelerators of brain cells, respectively, Colasin explains. Brain cells need both to function well, but when the accelerator gets stuck and the brakes don’t work, brain cell activity can run out of control and lead to seizures.
Although many antiseizure drugs act on these control systems, Colasin thinks that letting microbes take control of the GABA-to-glutamate ratio could provide a more fine-tuned treatment for some people without the side effects that accompany many existing drugs. “These bugs have coevolved with us for millions of years,” Colasin says. “And we are not seeing any evidence of side effects at this point.”
Bloom is also considering how the microbiome benefits of the ketogenic diet could be helpful in other neurological conditions, including autism, depression, and Parkinson’s disease. “It is early days, but we are excited about the potential,” Colasin says.
CORRECTION: This article was updated on June 5, 2018, to correct the company name. It is Bloom Science, not Bloom Sciences.