THE MICROBIOME SUMMIT : The Paradigm Shift
Mental Health and Brain-Microbiota Axis
Dr. Jane Foster, PhD
There are several ways in which our microbiota can communicate with our brains – including the many different pathways between the gut and the brain which are important in health and disease. In this interview, Dr. Jane Foster will discuss how differences in gut bacteria may be implicated in the various types of mental health conditions, what we know about the potential role of bacteria to influence anxiety-like behaviour, and new possibilities in “psychobiotics” – probiotics that could confer a mental health benefit. Dr. Foster will also discuss how advances in microbiome research may also uncover why some people develop certain conditions and others may not – and which treatment approaches may work best.
- Tracey:
- We are here at the University of Toronto with Dr. Jane Foster, from the Foster Lab at McMaster University. Thank you for joining me.
- Jane:
- Thank you for inviting me.
- Tracey:
- You and your lab have been doing some very interesting work on the gut – brain connection. Looking at what the microbes are doing, specifically. Now, this started out as just a mere hypothesis and then we went into mouse models and we are moving into clinical studies. Can you tell us a bit about what these microbes are doing and what we understand to date?
- Jane:
- So yeah, so the microbiota-brain axis is really sort of an emerging topic, particularly in my lab related to neuroscience. So, I guess early research showed that microbes were important to nutrient metabolism in other fields, but in the last five years the neuroscientists have started to pay attention, and we have actually learned, both in mouse models and in human studies that they are linked to mood and emotional response. And so, we’re very interested in how the microbes might be communicating with the brain to influence behavior.
- Tracey:
- Yeah, it’s such a fascinating thing to make that connection. I mean, we never really understood how much of a role the gut microbes were playing in how we thought and felt. So, can you explain what, what mechanisms are they working off of?
- Jane:
- So, we know a lot – or we have historically known a lot – about top-down control. We know that the brain communicates with our whole body and influences everyday physiological processes, and that is a neural connection. So, both through our autonomic nervous system, and from the gut bacteria to the brain there is also neural connections that are sensory nerves and other bidirectional nerves linked to the autonomic nervous system, but also linked to our second brain in our gut which is the enteric nervous system, which directly samples the lumen of the gut by having processes right near those gut lining cells which are called the enterochromaffin cells. And so, the products that are produced by gut bacteria can communicate with the lining cells, they can communicate with the immune system, they can cross the barrier and get into the bloodstream. They can metabolize foods and other particles and produce metabolites that then can communicate locally and remotely. So, there are all these different ways that gut bacteria can communicate with the brain, including through soluble mediators that might go through the blood and talk to the barrier cells in the brain, or through leaky spaces in the brain or across the gut barrier. Bacteria themselves or their products can cross the barrier and that sometimes can affect how our inflammatory tone is in our body and that change in inflammation can influence that immune-brain communication. The immune cells themselves is one of the things my lab is interested in, and they can be educated by the bacteria in the gut and that can influence how they communicate with the brain. So, there are a lot of different pathways between the gut and the brain and all of them are probably important in both health and in disease.
- Tracey:
- Right. Do we have any understanding yet as to whether or not there is a difference between, you know, whether or not somebody gets depression or anxiety or both or suffers from PTSD. Do we understand what the gut microbes look like, or might be doing?
- Jane:
- So clearly these different disorders linked to mental health are distinct in some ways. But when we think about the biology underlying them there might be some shared biology across disorders and with respect to the microbiome and the brain, most of the evidence to date points in the direction of anxiety. Particularly in the mouse models that changes in your microbiota might influence anxiety-like behavior or exploratory behavior specifically. That’s the strongest evidence. There is some evidence that when stress occurs and changes the microbiota, that changes depressive-like behaviours in rodents. There’s been a couple of papers in depressed patients. There has been at least one ongoing study that I know of in anxiety patients, and some of those changes could be similar. There’s not really enough evidence yet to point to which specific bacteria might be important in each of those separate states. And whether or not those clinical diagnosis are homogeneous is not really the nature of the beast today. So, we think that some of the heterogeneity that happens in mental health might be linked to the gut bacteria and in different people there might be a different change. So, for example in one person they might have a barrier change that influences inflammation, in another person they might have a neural change. So, all those pathways that we were speaking about could be different in
different individuals that might be diagnosed with the same clinical condition. - Tracey:
- Interesting. Now for a clinician and our clinicians that are watching are sitting there going, well how would I figure that out?
- Jane:
- Yeah so I guess that, clinically we don’t yet have a test to say, “Is this your gut bacteria versus something else?”, but there’s a lot of different factors that influence gut bacteria so for example diet, exercise, age, these are all important factors – stress! So certainly, you know, sometimes people have changes in microbiota that result in a change in G.I. function, so monitoring G.I. function might be helpful to, sort of in a blunt way to see that the gut might be involved, but just as importantly might be changes where there is not a gut disturbance and those are the ones that we need biomarkers. So, a lot of the research in clinical patients as well as in the animal ones right now are looking for these biological signatures that help us reduce the heterogeneity in the patient population or in the human population in order to better understand what can we measure that would identify, are you a person that would sort of respond to diet, exercise or some sort of probiotic or prebiotic that might benefit your bacteria in your gut.
- Tracey:
- Right. Now when we are talking about, you know any of the depression or the anxiety, doctors generally are not asking about diet or lifestyle factors per se, like “how much do you exercise?” or “what are you eating?”. Are these things that the research is telling us that we really should be paying attention
to? - Jane:
- Yes, what I think in clinical research there has been a real move in the mental health, particularly in mood and depression, to start integrating some of these diet questionnaires and food frequency questionnaires. And I know that there’s, even in, maybe more in the clinical psychology side there’s been some work on running groups and thinking a little more about the whole person from a treatment perspective. I think that we need to move into sort of a broader scope of considering how many factors might influence overall health, and some of these are actually better targets then pharmacology.
So, I think that there are individuals who would self-select, to be in that group and I think probably as we, you know, we don’t really teach in medical school yet some of these alternative approaches and I think that’s probably the place that needs to be thought about, is you know, what are the alternative ways to assess the differences or the heterogeneity in those individual patient populations, because that really is what we are talking about. - Tracey:
- Yeah, it makes a lot of sense, yeah. There is a term, “psychobiotic” and I understand, you know, that this is something that people around the world are a little bit excited about. Is there a type of probiotic that could maybe be used to influence the microbiome to treat anxiety or depression or other things on the spectrum? What are your thoughts on that?
- Jane:
- Well I think that one of the exciting things about the field and one of the reasons why it’s moved forward so quickly is the fact that people have demonstrated in animal models that probiotics have a beneficial effect to anxiety and depressive-like behaviors in a variety of models. But also work has been done in clinical populations and in healthy volunteers to demonstrate that taking a fermented milk product full of probiotics or other probiotics, that there is actually a benefit to mood, to aspects of mood, and with the work that Emeran Mayer has done with neuroimaging actually a change in the circuitry of the CNS (central nervous system) in the brain in response to a beneficial probiotic. So, there’s a lot of hope linked to the idea that probiotics might in fact be a good treatment for individuals with mood symptoms. Whether it’s a stand-alone or it’s an augmentation, that would have to be determined but another interesting aspect of that, and less work has been done is the concept of a prebiotic or these, fibers that we take in, in our diet that promote the growth of good bacteria and so there is some animal work in that domain and there might be actually some work out there that’s not connected to microbiome in diet research but some of these manipulations that promote good, positive changes in commensals or in good bacteria that would facilitate mood is a very hopeful area of research.
- Tracey:
- Yeah. I wanted to speak to you specifically, because your lab is doing some very interesting work about perhaps there might be some connections between our own human genetics and what’s happening with the microbiome. Now if we go back to the early 2000s, the human genome project was finishing up and everyone was super excited that we would have a lot of answers and then it was sort of like “mmm…you know we have got this whole micro biome that we haven’t really considered” and so the pendulum sort of swung over to studying the human microbiome, but maybe the two are meeting somewhere. Can you explain some of this work that you are doing?
- Jane:
- Yeah so what is really interesting to me in my group is some of the recent findings that suggest in fact our own hosted genetics or our own DNA that we inherit influences the composition of the bacteria in our gut in so the ideas that are emerging are based in the fact that, for example, in mice, different strains of mice have different profiles of gut bacteria housed in the same environment or others. And there are human studies who also suggest that in fact the DNA that we are born with influences the composition of the gut. But what we don’t know right now is how much is contributing from our DNA make up and how much is contributing from the environment, such as stress or diet or other components. And so, understanding the balance between host genetics and environment, or this gene environment interaction piece is going to be a very important finding in the next few years to help us really think about how is it we can use that information to effectively treat individuals with or without manipulating the microbiota.
- Tracey:
- Right, so interesting. Can you give me an example of how that might look, this interaction between our human genetics and the microbiota?
- Jane:
- Yeah so, I think that one of the things that people who study gene- environment interactions have been interested in is the idea of, what aspects of the phenotype we are looking at? So, when I look at myself and I say I have increased anxiety, or I have a little bit of extra weight, is that because I was born that way or is that because of something that has happened along the way. And so, I think understanding how much of that is contributed to by genetics and by environment may also be housed in the gut bacteria. So what if our, the composition of our gut is actually a good representation of our environmental history and our genetics. And so, by taking a look at for example the composition of diet might be more plastic and amenable to changes in diet or pharmacotherapy, or some other approach such as exercise that might be able to be more precisely matched to the person. Which is sort of the move of this precision medicine that is coming on board.
- Tracey:
- Right, yeah, and from a clinicians point of view, we can’t figure these things out unless it becomes part of our mainstay toolbox in medicine. Until we start delving into the lifestyle stuff and actually tracking these things in our patients, we can’t really answer these questions.
- Jane:
- Yeah so, I think that that’s the important part of some of the research initiatives that are happening in these interdisciplinary and translational groups. The idea of measuring some of these blood, fecal samples or biopsies from patients and really getting a clear understanding of which bacteria or which, what’s the function of that bacteria and how those influence both health and disease is really what’s happening in the next few years in the field.
- Tracey:
- Thank you so much for sharing all this information with us.
- Jane:
- Thank you.
