The Potential of Altering the Gut Microbiome for Brain Health


Daniel Lowenstein, MD, professor of neurology and executive vice chancellor and provost at the University of California, San Francisco, discussed the ongoing trials and steps being taken to turn the gut microbiome into a realistic therapeutic option for patients with epilepsy.

Daniel Lowenstein, MD

Daniel Lowenstein, MD

This is the second of a 2-part interview. Read part 1 here.

The connection between the gut microbiome and brain activity has increasingly drawn interest from epilepsy specialists, provoking them to conduct further research to uncover therapeutic possibilities. At the 73rd annual meeting of the American Epilepsy Society (AES), December 6-10, 2019, in Baltimore Maryland, Daniel Lowenstein, MD, discussed the progress made in this research, further demonstrating a strong connection between the gut and the brain.

Lowenstein, who is a professor of neurology, executive vice chancellor, and provost at the University of California, San Francisco, where he previously served as the director of the UCSF epilepsy center and epilepsy research laboratory, detailed how some of the research demonstrates a profound connection between the gut and overall health, and how each individual's gut environment influences their susceptibility to various conditions.

In part 2 of this interview, Lowenstein helps us to understand the gravity of the potential impact that altering the gut microbiome might have on not only brain diseases, but health in general.

NeurologyLive: Are there any microbiome studies currently ongoing that show potential promise?

Daniel Lowenstein, MD: I'm not a microbiome specialist, but I've been encouraging a lot of people here [at AES 2019] to pay attention to it. There are so many potential important interactions between the microbiome and the brain and its excitability and ultimately, the likelihood of having seizures or developing epilepsy. One other example—in addition to what Elaine Chow, MD, found—was what Andrey Mazarati, MD, PhD, has shown, which is in a model of traumatic brain injury which leads to epilepsy. He has data to suggest that the traumatic brain injury itself alters the microbiome in a way that if you take the altered microbiome and put it into another animal that hasn't had the brain injury, it actually has increased susceptibility to seizures. That's pretty crazy, isn't it?

Those are just two examples. There are an endless number of questions that arise out of those primary discoveries or observations. Now they need to be reproduced. They need to withstand the test of time. But if these and other types of early studies are shown to really be robust, then there are just endless numbers of questions. For example, what's the effect of the microbiome when our patients take anticonvulsant drugs? Each of us has a unique microbiome. It changes from day to day, month to month, year to year. We have a really difficult time understanding why there's so much variability in the response of our patients to treatments that we're giving them—they have good periods and bad. Could 1 of the problems be that we don't understand the underlying dynamic state of the microbiome? It's actually affecting the metabolism of the incorporation of the drugs that we're giving them by mouth. That would be one.

Another huge area is how does the variation in each of our microbiomes lead to the threshold for excitability in our brain, given that the microbiome is releasing or causing the production and metabolism of neurotransmitters and inflammatory mediators and so forth? The last area doesn't have to do with epilepsy specifically, but most people, I don't think, appreciate the fact that when we are formed as a fetus, our immune system is in a very nascent state. It hasn't been exposed to the outside world, right? That primarily happens the moment the fetus passes through the birth canal, and then gets its first exposure to the bacteria, viruses, and other things that are out there—the antigens in the outside world. Well, that moment is the beginning of the setting up of the infrastructure of our immune system for the rest of our life. The fact that you and I have different immune systems, in part, is because of the uniqueness of each human’s exposure to the outside world.

As an example of how powerful this is, there's an investigator named Susan Lynch, PhD, at the University of California, San Francisco, who is a microbiome specialist. She's done a series of studies where she's taken the stool samples from infants at just 2 to 3 months and stored them, and then followed the children for a number of years. The whole idea of these studies is to see whether there are characteristics of the microbiome in early life that might be predictive of disease later because if your immune system is being affected by that early microbiome, it might be connected to immunological or immune mediated diseases later. She did this and what she was able to show is that if you look at the microbiome characteristics at age 2 months, you can predict, with almost 80% certainty, the likelihood of developing asthma at ages 3 or 4 years. We haven't even begun to look at how that applies to the world of epilepsy, but I think it's yet another example of how it's groundbreaking.

How realistic is it to potentially alter the gut microbiome as a therapeutic option for a condition such as epilepsy?

It seems like eminently feasible because, just as a starting point, we're changing our microbiome all the time based on what we eat. If you go from whatever your regular diet is to a ketogenic type of diet, you're changing your microbiome. We know that it gets altered physiologically. On the more extreme end of the spectrum, people are beginning to use fecal transplants. They're ablating the microbiome in patients, in part, because they're on antibiotics. The treatment for C. difficile, for example, is to ablate and then do a transplant to try to repopulate the gut with the appropriate microbiome. To me, those are those are 2 examples that have been occurring for a long time now.

The possibilities are endless. We need to understand much more about the basic biology of the microbiome, but I have no doubt that over the coming decades and beyond, this is going to become a regular part of not just sustaining good health, but also in the treatment of disease.

Transcript edited for clarity.

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