Elaine Hsiao, Biologist
Can the Bugs in Your Gut Affect Your Brain?
Bugs are not things that interest most of us. But for Elaine Hsiao, a microbiologist at Caltech, they are an endless source of fascination and a possible key to revolutionary new health therapies. Speaking from her lab at Caltech, Hsiao explains how the gut and the brain are intimately connected through microbes, how microbes affect our immune systems, and how one day they might be engineered to treat psychological disorders like depression and autism. —Simon Worrall
How did you get interested in microbes?
[Laughs.] I first became interested in microbes as an undergraduate at UCLA. My major was in microbiology and immunology. At that time, I was interested in pathogens. I was really amazed by how they seemed so smart; they could evade the immune system and figure out really neat ways of surviving and tricking our normal bodies into thinking they're not there. I don't really study pathogens now. I study the microbiome, the normal microbes that live in and on us.
If you were to look inside my gut, what would you see?
If I looked into your gut I would see trillions of microorganisms grouped together in different communities and very active and dynamic. Not only bacteria, but also viruses or resident fungi or protozoa. It is estimated that if you packed them together they would weigh the size of a pretty hefty organ—so two to six pounds.
Your work is about how microbes in the gut influence our brains. Explain, please.
It sounds like a wild idea at first. But if we step back and think about infection, in the form of pathogens or parasites, there are lots of examples where they can change the brain or behavior. Think stomach flu. There are lots of behavioral and mood-related changes. Now we're extending this to normal microbes, and what they might be doing to affect our brains and behavior.
"Gut feeling" and "gut instinct" are phrases we use every day. Are you discovering a scientific basis for them?
It's a tricky question. We like to say "gut feeling" because it's a cute way of expressing how we behave or feel. But gut feelings are in part intuition, which may be encoded just in the brain. We aren't investigating gut feelings and intuition per se. We're investigating how normal microbes in the gut can affect other mechanisms, like memory, sociability, or communication.
You use the phrase "mind-altering microbes." What do you mean?
In the past decade, there's been so much science that's revealing how normal microbes play an important role in regulating our behaviors. This is mainly from studies on animal models. We can raise animals in completely sterile conditions, so they're otherwise normal but just lack resident microbes. When you compare behaviors of animals raised without microbes and animals raised with normal microbes, there are striking differences in how they behave and function.
How is our immune system affected by the microbes in our gut?
The immune system is hugely affected and regulated by gut microbes. This is a rich area of current study. Many investigators are finding particular bacteria, or groups of bacteria, that influence the balance between inflammation and immunosuppression. The next frontier is to study how these micro-mediated immune changes affect the nervous system and what other pathways may be involved.
Could microbes one day be used for psychological therapy, say to treat depression or autism?
That's the long-term hope. We're really at the early stages but the evidence is really intriguing as to how we could use microbes to impact behaviors or symptoms relevant to neurological disorders, like autism and depression. Much more research remains to be done, but the hope is that in the future we might be able to uncover some basic mechanisms and learn how to use microbes to treat disorders.
What would the advantage of microbial treatments over regular pills and medicines be?
That also remains to be determined. Probably the most promising prospect is that a microbial treatment, if it involves live microbes in the gut, could confer long-term benefits. This would be a live therapeutic treatment, where the bacteria would colonize and take up residence in the gut and hopefully continue to provide benefit. There's a potential to engineer bugs to use as vehicles for delivery of a medicine to promote the immune system.
You are working on mice at the moment. How close are you to rolling this out into the human world?
Our lab is particularly interested in studying basic mechanisms by which microbes can influence the nervous system. The mouse turns out to be a great model system for that. There's a lot that we can't study in living humans. So we start with mice and try to translate what we find to human samples. We often make use of human microbiome samples or human cell culture samples to test in the lab. There is currently a lot of interest in studying probiotic or micro-based therapeutics in clinical trials.
What inspires you in your work?
What I find really inspiring is learning about the mechanisms of basic biology, and using this knowledge to hopefully make a real impact in health and disease.
In Their Words
What inspires me is learning about basic biology, and using this knowledge to make a real impact in health and disease.
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