THE MICROBIOME SUMMIT : Impacts of Sanitizing Our World

Diet, Depression and the Microbiome

Dr. Felice Jacka, PhD

Deakin University

Overview
Transcript

Overview

How are diet, depression and the microbiome all connected? The role of diet in mental health has been overlooked for too long. Felice Jacka is an expert in the emerging field of nutritional psychiatry. In this interview, Dr. Jacka discusses how diet, depression and the microbiome are intimately connected – changes in diet can shape our microbiome, and ultimately our brains. (For example, eating junk food can shrink a part of the brain called the hippocampus.) It is necessary to eat for your brain and microbiome, and food has the ability to shape the balance of microbes in the gut in as little as 24 hours. Hopefully in the future, dieticians will be a part of mental health treatment teams.

Transcript

Tracey:
We’re here at the University of Toronto with Doctor Felice Jacka. She has her PhD in psychiatric epidemiology, she is an associate professor at Deacon University in Australia, and she’s joining us here today. Welcome.
Felice:
Thank you, thanks for having me.
Tracey:
Can you tell us about some of the projects that you’re involved in, and what you are up to in your career right now?
Felice:
Well, I’ll tell you about a study that we did last year that I thought was absolutely fascinating, and really very important. And in this particular study, what we had were brain scans from several hundred older Australian people.
Now, we’d already shown, in this big study, that the quality of older people’s diets was related to their likelihood of depression over time, and that that seemed to be quite independent of their socioeconomic status, financial status, etc. When we found out that we had access to this MRI data, I really wanted to look and see whether the same thing was true in humans that is true in animals. So, remember I was saying that there were lots and lots of studies coming out of the U.S. showing that if you, for example, fed rats or mice things such as sugary foods or high fat diets, it would have a really negative impact on proteins in the brain that we call neurotrophins. And what they do is they protect neurons in the brain, the ones that are already there.
Tracey:
Right.
Felice:
But they help to promote neurogenesis, which means the growth of brand-new, baby brain cells. Now, where that happens most in the brain is an area of the brain called the hippocampus. The hippocampus is critical for learning and memory, but it also seems to be very important for mental disorder, particularly depression. So, when people are depressed, their hippocampus shrinks.
Tracey:
Interesting.
Felice:
When they are successfully treated, the hippocampus grows again, and that obviously has implications for their cognitive functioning.
Tracey:
And this can happen throughout your life.
Felice:
That’s exactly right. They can grow and many things influence levels of these neurotrophins, which are like the manure for the new brain cells, and then that, of course, in turn, affects hippocampal function, which is learning and memory, and also risk for mental disorder and hippocampal volume, and the two are linked. So, in the animal studies, it’s very clear that diet and exercise seem to really have an impact on hippocampal functioning, and on levels of these neurotrophins. So, I wanted to see whether there was a link between the quality of these older people’s diets and the size of their hippocampus. And we looked, and there was a very clear relationship, exactly as we’d predicted. So poorer, unhealthier diets, people had smaller hippocampi, particularly on the left hand side of their brain. And the ones who had healthier diets, their hippocampal volume was larger. And this wasn’t just a trivial effect, this was a really large effect.
So, what it’s saying is that diet is really important for brain health. Now, that’s important when you’re older and you’re thinking about dementia and cognitive decline.
But of course it’s important across the age range. It’s important for children going to school and trying to learn and remember. This is about your brain power. So, it gave rise to a lot of really interesting headlines around the world, and one of them I really liked, which was, “Junk food shrinks your brain,” and you know, that is something to really take away. And it has an immediate impact on your brain health.
Tracey:
I think that’s so important to realize.
Felice:
But there was also a really nice study where they actually took middle-aged, healthy men. How healthy? They were a bit sedentary, but otherwise they were healthy. And they put them on a junk food diet for a week. And what they found was they had similar deficits in their spatial memory, that’s linked to the size of the hippocampus, within just that one week.
Tracey:
Wow.
Felice:
Now, we know that after only one week, in animal studies, if you feed animals a junk food diet, you get neuroinflammation. That means, like, the immune system in your brain is inflamed. It’s really going to have a big impact very quickly.
Tracey:
In one week?
Felice:
In one week. And we also know now, with the gut microbiota which we’re now understanding is absolutely essential to our immune function, to our metabolism, our body weight, but also, we’re starting to understand, for our brain health, and mood and behaviour, that you can change gut microbiota composition and activity within 24 hours by initiating dietary change.
Tracey:
Wow.
Felice:
Particularly when you’re manipulating the levels of fats and fibre. They’re the two really key aspects of diet, it would seem.
Tracey:
Now, you go on vacation, and you eat poorly, for a week or so. That’s enough to affect it?
Felice:
It looks like it, yes. I mean, what we know about everyone’s gut microbiota fingerprint is very different. Mine would look very different to yours. There’s lots of things that influence—probably genetics has something to do with it. But the thing that determines your enterotype, which is your fingerprint, we think, really relates to diet, but it’s long-term diet. Long-term dietary patterns are very important.
Tracey:
Right.
Felice:
So, when we’re born we have a very immature gut microbiota. We get that from our mother. And then, over the first three years of life, three or four years of life, it gradually establishes its own fingerprint. And we know that the child’s diet in those first few years is critical to what is set in place. And then you kind of carry that with you across your life.
On the other hand, we see, from many experiments in animals and in humans, that you can change the gut microbiota pretty profoundly by making a big dietary switch. There was a really, really cool study, published not that long ago, where they looked at the diets of African Americans and people in rural Africa. And of course, as you can imagine, their diets differed enormously. The people in rural Africa, like many people in Africa, much higher in plant foods and fibre, and much lower in, well, obviously, processed foods, but then unhealthy-type food products.
Whereas the African Americans’ terrible western diets, typical diets that you see—I mean iin the States, nearly 60 percent of Americans’ energy intake is derived from ultra-processed food products. They’re not food.
Felice:
So, they looked, and of course, the rural Africans and the African Americans had very different gut microbiota profiles, and the African Americans had quite unhealthy gut profiles; lots of markers of inflammation that are linked to cancer risk and bowel cancer risk. And the rural Africans had less of that. And then they got them to swap diets for two weeks. And it was amazing, the impact that that had within two weeks. And for the African Americans who got swapped onto a healthy rural African diet, their markers of cancer risk went right down. Whereas for the poor old rural Africans getting a western diet, they went right up. So, that tells us that you can modify diet and modulate your risk for disease pretty quickly.
And there’s a whole host of things in junk food, not just the fats and the sugars that we think, or we’re starting to understand, are really noxious to the gut. So, the inside of your gut lining should be relatively impermeable. It’s got a layer, a mucosal layer that protects the inside of the gut and keeps the contents of your gut where it’s supposed to be, in the gut. Lots of different things can open up what we call the tight junctions and allow the contents of the gut to get out into the bloodstream. So, that’s bacteria, undigested food products, and toxins and things. And then your body goes, “Hang on, what are all these things doing in my bloodstream? I’m going to mount an immune response.”
Tracey:
You’re talking about leaky gut, now.
Felice:
That’s right, leaky gut. And what we’re starting to understand is that emulsifiers that are in virtually every single processed food product that you can think of, even the healthy ones, strip that mucosal lining, and therefore are much more likely to afford this opening of the tight junctions and the leaky gut.
Tracey:
Wow.
Felice:
And—yeah. And then we also know that artificial sugars seem to change the gut microbiota in a really noxious way that prompts weight gain. So even though it’s not real sugar, it still might make you fat.
Tracey:
Right.
Felice:
So, this is what the early studies in the animals are starting to show us. Over and over again, they’re showing us this. So, there’s aspects of processed foods that are not even the obvious bad things, like the trans fats or the added sugars, that may be really noxious to your gut, which in turn, then, has a huge impact on your health, because the immune system is central to, you know, virtually every aspect of your body’s functioning, and disease risk.
Tracey:
Right. Do we know exactly the role the microbiome is playing in all of this? Do we understand the inflammatory processes that may be affecting the brain? What do we know?
Felice:
Well, you know, medicine is incredibly complex, and the human body and health is probably as complex and hard to understand as deep space is, and we’re finding out more and more things all the time. Because so many people are turning their attention to this issue of the gut microbiome, it’s really a whole new paradigm in medicine.
Tracey:
It is a new paradigm.
Felice:
New frontier. It’s opened up because we finally have the tools to be able to actually look at this. So many, many people all over the world are putting their attention into trying to understand this. So, we do know a few things now.
And so, things in the environment that bring bacteria into us, like contact with the soil, and with air and trees and water, where you’ve got lots of microbes, that’s a good thing. Traditional foods that have lots of fermentation, they seem to be really helpful. But what we do know, and I think that this is really key, and it’s actually quite simple, is that when we eat fibre, plant fibre, the bacteria ferment that fibre, and the fermentation process results in these products called short-chain fatty acids, and they seem to be, absolutely, the drivers of immune function. Now, we should be having about, well, certainly a minimum of about 50 grams a day of fibre for the bacteria to be able to do that.
Tracey:
Wow.
Felice:
Most people in the west get about ten grams of fibre a day.
Tracey:
That’s right, yeah.
Felice:
It was an amazing study, published just a few weeks ago, and what they did was that they got mice, and they fed them a low-fibre diet. And then they fed the mice’s children a low-fibre diet.
And they did that for four generations. And what they found was that after four generations of a low-fibre diet, so much of the bacterial diversity was lost, and it could not be rescued even when they reintroduced fibre. That was it, it was gone. So, this intergenerational transmission of disease, keeping in mind how badly we’re eating, and that people are losing the knowledge about how to prepare food, and cook, and even shop.
Tracey:
So we had microbes become extinct.
Felice:
Pretty much. So, they were just lost. So, all that diversity was lost, and that has real implications for our health. So, very simply speaking, we do know is what you eat has an important impact on your immune function via this fermentation process. So, that’s one thing we know, so far.
Tracey:
Okay.
Felice:
What we also know is that there’s a very important, highly active, bidirectional relationship between the brain and the gut. It’s called the gut-brain axis..
Tracey:
Right. So, if I am a mental health professional, I am, you know, I’m hearing what you’re saying, and I’m like, “Okay, so does this mean I put away my prescription pad and I start talking to my patients about their diets?”
Felice:
Look, I don’t think it needs to be a dichotomy.
Tracey:
Okay.
Felice:
And I think that’s a really critical thing. You know, something like depression—apart from genetics, there’s no one factor that accounts for a great proportion of what we call the variants in depression. So, lots of things, small things, contribute. It’s what we call a multifactorial disorder. One person’s reason for being depressed could be entirely different to someone else’s reason for being depressed.
We don’t yet know enough to know how important diet, and maybe exercise, things like that, are.
This trial that I told you about, because the effect size was so large, the difference between the groups was so pronounced, that would suggest that diet is actually really important, much more so than we thought. But that’s only one study. We need many more studies to be able to really quantify that. And it certainly doesn’t need to be either-or. You know, about 30 percent of people will respond very, very well to, say, anti-depressants, 30 percent of people, roughly, will respond very, very well to psychotherapy. We’ve just had colleagues of mine published last week, in the American Journal of Psychiatry, an important meta-analysis, where they pulled together all of the data and looked at it in great detail, and showed that there’s certain supplements that are very useful as an adjunctive therapy. That means that while you’re taking your other therapy, whatever it might be, if you take, say, fish oil as well, that seems to give that treatment a boost and help it to work better. Folate, some vitamin D, these ones seem to have an evidence base to suggest that if you take them alongside your other treatment they’ll really help.
So, when it comes to diet and nutrition, it’s the substrate. It should be the first thing. Exercise, sleep, diet, smoking. Those four things really should be the first thing that is looked at, because they are probably the risk modifiers. You know, in the face of other environmental factors that may or may not trigger depression, they’re things that a, you can control, and b, you might moderate the risk, up or down, of whether or not you develop depression, in the face of other risk factors. So, we would certainly not expect that people would just throw away their prescription pad and go off and do a dietary intervention, but it might be extremely helpful to do both. For people who don’t want to take medication, it might be something that they would try. And certainly, it could only be beneficial.
When we think about the burden of disease, we think about the fact that, well, certainly in Australia, only about ten percent of women and five percent of men adhere to the basic dietary guidelines.
Tracey:
Yeah.
Felice:
Everyone’s eating badly. It doesn’t matter that there’s all this wonderful food available. The impact of industry on the way we’re eating is so profound that everyone’s eating badly. So, learning how to eat well and getting some support to do that is only ever going to be beneficial. But it may well be that we start adding dieticians to the multidisciplinary mental health teams. It may be that people can go and see a dietician as well as a psychotherapist.
There’s a whole range of things that I think will probably start to change once we recognize that this is actually an efficacious way of treating depression.
Tracey:
So how do we know that we have the diet information right this time? Because we’ve been led down the wrong path before. We spent two decades or more following low fat recommendations. So how do we know this time?
Felice:
We don’t. So really this is the thing that we are increasingly understanding that there is no right diet for everyone. People respond very differently to different diets. We hopefully will be able to, with new mathematical techniques even, big data techniques and all this information on the microbiome, and other information about people’s body weight, genetics, their food and exercise etc, start to develop algorithms that might help us to predict how people will respond to different diets. And we may be moving towards that individualized nutrition. A lot may depend on the state of people’s gut to begin with, the gut microbiota, because they really control metabolism and determine what nutrients are taken from food for example.
Tracey:
And that they inherited from their mothers.
Felice:
That’s right and of course there are all sorts of things there we can consider around how important mothers’ diets are not only to their own health to the mental and physical health of their children but to the health of their gut microbiome which they pass onto their children.
And this is another really key understanding. The early gut microbiota of a newborn is absolutely central to their brain development, and the development of their immune system. We know this from these new experimental paradigms called germ-free mice. This is where you breed mice kind of in a vacuum. They don’t have any of their own commensal bacteria. And we know that they differ enormously on their stress response, their brain plasticity, a whole range of factors. And what we know is that the brain development is impaired when they don’t have gut bacteria. Then, of course, the development of the innate immune system is impaired because the gut microbiota seem to be really central to that.
Now, if you consider that babies get their gut microbiota from their mothers, it’s really important that mums’ microbiota are healthy. Also their vaginal microbiota. I mean, there’s microbiota all over your body. They’re profoundly affected by stress, that’s another thing.
Also, of course, antibiotics, which you use widely through industry, the food system, they’re given to pregnant women as a prophylaxis. Children in very early life often get an antibiotic prescription for an early, you know, medical event.
And that seems to have a really profound effect on the microbiota. So, there’s real implications for this new body of knowledge. And of course, on the other hand, and thinking more positively about it, there’s a huge amount of effort going into trying to characterize what a healthy gut microbiota might look like in a newborn, so that then you can deliver a prophylactic dose of probiotics to kind of start them off right.
Tracey:
We aren’t there yet, though. Is that correct?
Felice:
No, but I don’t think we’re that far away with that, because of course, industry is putting all its attention here. Because if we know that this is a powerful way to actually prevent disease and to set babies up well, you know…
Tracey:
Through the microbiome.
Felice:
…it’s not going to be the saviour for everything. You know, people still need to really consider their diet. The early gut microbiota for an infant is enormously affected by the food that it starts eating once it starts eating.So you have to get that right, as well.But it might mean that we might be able to give them a bit of a head start.
Tracey:
I think that is so important. Thank you so much.
Felice:
It’s a pleasure.