Q&A with Phil Strandwitz
Satori Neuro: Your company, Holobiome, is dedicated to discovering and developing therapies, including for mental health, from the human microbiome. How should we be thinking about these types of interventions compared with traditional drugs?
Phil Strandwitz: There are three main differences that come up for me. First and foremost, the microbiome may be actually causing these disruptions, so it’s explanatory and well as being a way for us to actually fix it by tackling the root cause. The more we study it, the more we find associations. It may just be one piece of the puzzle, but it looks to be an important one as we think about memory formation or behavior through the lens of depression, anxiety, and neuroinflammation. That last one is tied to ALS and other things like Alzheimer’s, Parkinson’s, motor dysfunction…it’s all starting to be connected.
Secondly, through use of medicinal chemistry, scientists are good at developing artificial small molecules as drugs, but we can actually use microbes that nature created—that we co-evolved with—to target the same biology those molecules are going after. Where I’m really bullish about the microbiome is it’s one of these unique situations where it has a high probability of being inherently safe. You’re pulling microbes from healthy people and putting them into other people. These microbes have also been with us a long time: you can get ancient fossilized poop and sequence it, and you’ll see microbes that you still have today, which is incredible.
And finally, drug development is often focused on one pathway, one disease, one symptom, but with human-derived microbes, you can deliver the superhero bugs into people or even change food to support bacteria that exist in your gut. That way you hit more than one pathway that probably matters for a disease or a cascade of symptoms. A good example is some of the naturally-occurring bacteria that appear to influence GABAergic signaling and neuroinflammation. It’s super hard to do that with a single molecule, and this is a way to embrace the complexity of us with the complexity of microbes.
SN: That brings us to the ecosystem aspect of this. Humans are not famously great at managing ecosystems. Is it realistic to think that in the future, specific diets can be prescribed for a specific problem and we could reliably create the outcomes?
PS: I think there’s a real possibility there. To use the analogy of a garden, the task is to find the right plants—and the right fertilizer—to add and make the ecosystem stronger. The reality is, though, we don’t quite know what are the right plants to put into people. This is what we’re trying to figure out. And once we get those seeds planted, those plants need food.
If you understand what food each member of the gut’s garden needs, and the ways each of those members can influence our biology and disease processes, for sure we can use food to improve it: It’s the source of most of our chemistry, after all. There’s already a ton of accumulating evidence that diet can be used to improve cancer outcomes. And the ketogenic diet for epilepsy and for bipolar is picking up a lot of momentum, as well as the Mediterranean diet for depression. In general, we have good evidence that a high-fat diet is not good for a variety of different things.
It’s strange how many people in the pharma space, in particular, pooh-pooh the idea that you could use diet to make an impact. I think it’s obvious you can, but you just need to understand a little bit more of the linkages from diet to microbes to health, as well as the direct link from diet to health. Then you can build a matrix and we can get to a place where, you need more energy or you have low mood? Eat this one. It’ll give you the plants to support it. I hope that’s where we get to eventually.
SN: How is Holobiome contributing to that future?
PS: Our goal is to help create a future where humans no longer have to rely on chance to get a good microbiome that prevents or cures disease. The founding team of Holobiome has been studying the microbiome since 2010, funded by one of the first grants in the Human Microbiome Project. What we, and others, have come to understand is there are around 5,000 species of human gut bacteria, but in any one person you might find 200-300 of those, so there is overlap in function. Going back to the garden metaphor, we’ve only cultivated about 1,000 of the plants and of those you can only buy 30 of them. That becomes a problem if you lose some of those plants (through bad diet or antibiotics, for example) and can’t get them back.
At Holobiome, we’ve created a strain bank of one of the most diverse, and ever-expanding, collections of human gut bacteria in the world. Now we’re taking large panels of these bacteria, rolling up our sleeves, and screening them in gold-standard drug assays to figure out which bacteria influence what aspects of host biology, and how they do it. We’ve also built some technology internally to help us explore complex communities, like a gut simulator, we can we use to study if our bacteria can “work” in the microbiome of diverse people.
From a commercialization perspective, we are collaborating with a large neuroscience pharma company on treating pain, as well as Unilever in the food space to improve stress. Our goal there is to get the right “plants” to the partners, and work together to co-develop them. Then internally we are looking at a single strain of human gut bacteria that looks like it has real promise for wellness, specifically for low mood.
SN: What do the timelines look like on those projects?
PS: In that internal program for low mood, we’re developing a consumer-facing probiotic, and next year we will run a 108-person placebo-controlled trial. If the data looks promising then we would look to find a large corporate partner for commercial development. After likely one more trial you would be looking at potentially having access to it in society within 18 to 24 months. Then in our collaboration with Unilever, they are fully funding a trial for us that reads out at the end of this year. We’re hoping to have two completed trials within the next 18 months or so, with the potential to see something in the market in 24 months.
SN: Any closing thoughts?
PS: When we look at neuro-related disorders—and there’s such a huge need there—we see two streams of possibility that could use investment and research. The preclinical data is screaming at us that microbes interact with the same biology that we’re trying to drug. And beyond that, we also see bacteria producing those same drugs. A few weeks ago, a paper was published showing that bacteria can directly produce braxanolone, which is Sage Therapeutics’ drug for postpartum depression. And that function is elevated in people who are pregnant.
SN: Oh, no way!
PS: Yeah. Super interesting stuff, right? Actually, the lead author of that paper has joined us as a scientist.
Philip Strandwitz is CEO and co-founder of Holobiome, a Satori Neuro portfolio company.