Hello and welcome to the Oxford University Department of Psychiatry podcast series. I'm Paul Cooper, and today I'm interviewing FSL Burnett. Hello. Hi. So thank you very much for talking to us today. So let's start off with. Can you tell us a bit about the work that you're doing with Prebiotics in psychiatry? First, maybe talk about some animal studies today and then go on to study.
So we're looking at these compounds called prebiotics, which are essentially nutrients for intrinsic bacteria, gut bacteria that's already present in our gut, the gut bacteria. And at the moment, what we're doing is looking to see how these properties interact with antipsychotics. Now, the main reason for that is that sometimes psychotics have unfortunate side effects that cause weight gain.
Patients and prebiotics have been shown to prevent weight gain in obese patients and something called metabolic syndrome, which which they also have. So we're looking to see Prebiotics might be a useful adjunct for antipsychotics to prevent weight gain in these patients taking second generation and subcortical, says one animal study. We are looking at the effect of prebiotics on memory in an animal model of Alzheimer's disease in collaboration with pharmacology.
That's still early days yet. And as far as human studies are concerned, we want to translate the antipsychotic prebiotic study to humans so we can see the effect of prebiotics in schizophrenia, patients who are taking antipsychotics and we're going to monitor their way to their immune function and so on. And again, this is all based on studies where we and others have shown that prebiotics affect the immune system,
affect metabolism, makes it more efficient and so on. Another human study we're doing is with children. We're looking to see if prebiotic administration affects children's learning abilities at school. And this is really come from animal studies where we've shown precognitive effects of prebiotics. And those are the main studies we do. So when you talk about animal models that you use to investigate this, how does that work?
Do you give the animals the antipsychotic and see what effects it has and then if the prebiotics can reduce that effect? Yeah, exactly. We inject animals with that. Sarkozy, which is a standard procedure in a drug investigation. We measure their weight, their behaviour and so on. And some animals will have an injection and the Previte other animals will have the with the injection of a placebo or something similar to a party which is known not to have a negative effect on the bacteria.
Can you explain the mechanism behind that prebiotics in their gut bacteria? Yes, that's a good question. There are a couple of proposed mechanisms which are currently being investigated. The first is the immune system. It is known to gut bacteria, train our immune system from birth, and it basically makes us less reactive to inflammation, if you like, and they sort of protect us.
So if we do have an infection, they help us fight that infection by perhaps outgrowing the pathogenic bacteria or causing the secretion of anti inflammatory molecules. Now, as we saw earlier last year, there is a direct connexion between the immune system and the brain is in Nature paper published about this lymphatic system, which allows these immune molecules and cells into the brain as we and others are looking at how bacteria modulate the immune system and therefore brain function.
Another method is a gut hormone and the gut bacteria. When they digest the probiotics, they actually release things called short-change fatty acids, which stimulate the secretion of gut hormones that tell us to stop eating well before these get hormones also penetrate higher sensitive brain. And they've been shown to have behavioural effects. So those are the two main effects.
There are other pathways which are being looked at. There's hardwired pathways such as the Faycal nerve connexion between the brain in the gut. But we're not looking into that other groups. So you've already mentioned the link between the immune system and brain function. There's a lot of buzz in the literature at the moment about how the immune system is linked specifically to psychiatric symptoms.
Do you think that going forward you could use Prebiotics to modulate, at least in some cases, psychiatric symptoms as well as the metabolic syndrome and things like that? Yeah, absolutely. We've already shown in animals that when we challenge them with an detoxing which models bacterial infection, we see post inflammatory anxiety in these animals.
And the animals had taken the probiotic. For a couple of weeks before we're resistant to this, so this was really something that was predicted in the reviews of our work, we're quite excited that we've already shown this. And since then, other groups have shown this as well. And this sort of ties in with the theory that there are Carpenteria trends or helps or fortifies our immune system.
So, yes, I think if there's a psychiatric disorder with an immune component, then prebiotics would be very helpful. Yes. Do you think that prebiotics will replace typical psychiatric medications in the future, or at least in some cases, right? Yes, I always get asked this and my answer always is, in my opinion, absolutely not. And I don't think they should. Drugs use in psychiatry. These drugs have their place and a lot of people function well on them.
And I don't think that nutritional substances such as Prebiotics are as powerful as these specific agents. Now, what they could do, they could help patients respond better to magnification. So always given with medication. But I don't see them as an alternative. And I don't think anyone listening who are taking these drugs should you should think they they want to take preventative probiotics. They should consult their psychiatrist position on treatment.
There's some discussion in the field at the moment about the effect of prebiotics versus probiotics. So what's your stance? Yeah, that's a good question. Unfortunately, a head to head comparison prebiotics probiotics has not been made to my stance is on the fence. I mean, certainly the reason why I was interested in probiotics is because I enhance all the good bacteria in our gut. Probiotics have specific strains that have been manufactured and you obviously can get now multi strain probiotics.
So you could argue that they might have limited effects because there's fewer stress. The maximum number of strains I've seen you can buy commercially. One capsule is about 14, whereas with Prebiotics you are amplifying thousands of different species. So arguably you could say Primo is better, but there hasn't been. That has a comparison. So we don't really know.
I think it's up to the person somebody might actually take probiotics who feel that it doesn't suit them and if they try probiotics, it suits them. It's all about the individual says something that is actually upset. Yeah. What is your academic background and how did it lead you to this area of research in Oxford? Yes, go back. I'm a biochemist by training. I did obviously in biochemistry. And I did an M.S. in neuroscience neurochemistry. More specifically, then, I did a Ph.D. in the same area.
But my first postdoctoral post was really about looking at neurotransmitters, specifically the serotonin neurotransmitter and behaviour, the molecular biology and so on. And when I came to Oxford, I came to Oxford and a MRC fellowship. I wanted to look at these neurotransmitters in schizophrenia. So then I started off looking at serotonin receptors in schizophrenia, post-mortem brain and of course, antipsychotics.
Since coming here in 92, I've been interested in neurotransmitter receptors, schizophrenia and psychotic drug actions there. What got me into this this microbiome field is that I started to look at the glutamate receptor that's been implicated in schizophrenia, the NMDA receptor that's proposed to be hyper functioning in schizophrenia. We've been looking at ways to enhance the function of this receptor, schizophrenia, using animal models and so on.
And one of the ways to do it is to actually directly give a Coalitionist of this receptor. And one of these coachloads, which is a key amino acid cordiality, is actually a component of the gut bacteria cell. So all the DNA in our bodies and a little bit in our brain comes from gut bacteria. So I thought, well, if we augment our gut bacteria, could we also augment the NMDA receptor function? So I contacted the prebiotic company and we got some money from the PBS to look at this.
And what we found is that certainly prebiotics did have an effect and did have an effect on the NMDA sector, as we hypothesised. But it actually was nothing to do with the. It was, as I said, probably immune system got warmer. So so although our prediction let it affects glutamate system in behaviour was correct, the media data is absolutely wrong because we were halfway there. So so that's what really got me into this field is the link with schizophrenia and empty receptors.
Is there anything that you've had to overcome to get to where you are today? Have you experienced any setbacks? Well, I've had many grant applications rejected as a supposedly activist, but I guess that may be the main thing. You've certainly come quite a long way. So is it just a case of perseverance? I think perseverance. We've had a new idea where we ask budding academic psychiatrists and psychiatric researchers to ask questions to our professors about their work.
So we've had a question from Thomas who says, I'm very concerned about the number of pathogens that can be detected or involved in the microbiota of people with mental disorders. There are a lot of genes in the genome. There are also a lot of organisms in the microbiology. This could lead in the same way to a false positive. The way to avoid that could be to make a very large study with very low statistical significance threshold.
Is there any organisation or consortium in this topic that could coordinate such a study? That's a good question. The answer is yes. The short answer is yes. There's actually the Human Microbiome Project, which started in 2008 at the National Institutes of Health in the USA, and the aim was to sequence the whole human microbiome in health and disease. This this facility allows researchers quite a few now on the microbiota to deposit their data about the microbiome and disease.
So if Thomas goes to the website, you see the workshops, there's information about this, and it's exactly to address that question. So I think quite soon, perhaps, and perhaps in 10 years or so, there will be information out there about severe psychiatric diseases and microbiome composition. OK, that's great. Thank you very much for speaking to us today as a pleasure. Thank you.