1
00:00:05,790 --> 00:00:10,410
Hello and welcome to the Oxford University Department of Psychiatry podcast series.

2
00:00:10,410 --> 00:00:14,190
I'm Paul Cooper, and today I'm interviewing FSL Burnett.

3
00:00:14,190 --> 00:00:18,200
Hello. Hi. So thank you very much for talking to us today.

4
00:00:18,200 --> 00:00:24,240
So let's start off with. Can you tell us a bit about the work that you're doing with Prebiotics in psychiatry?

5
00:00:24,240 --> 00:00:29,410
First, maybe talk about some animal studies today and then go on to study.

6
00:00:29,410 --> 00:00:35,820
So we're looking at these compounds called prebiotics, which are essentially nutrients for intrinsic bacteria,

7
00:00:35,820 --> 00:00:39,360
gut bacteria that's already present in our gut, the gut bacteria.

8
00:00:39,360 --> 00:00:47,640
And at the moment, what we're doing is looking to see how these properties interact with antipsychotics.

9
00:00:47,640 --> 00:00:54,930
Now, the main reason for that is that sometimes psychotics have unfortunate side effects that cause weight gain.

10
00:00:54,930 --> 00:01:05,400
Patients and prebiotics have been shown to prevent weight gain in obese patients and something called metabolic syndrome, which which they also have.

11
00:01:05,400 --> 00:01:10,890
So we're looking to see Prebiotics might be a useful adjunct for antipsychotics to

12
00:01:10,890 --> 00:01:15,420
prevent weight gain in these patients taking second generation and subcortical,

13
00:01:15,420 --> 00:01:17,130
says one animal study.

14
00:01:17,130 --> 00:01:26,160
We are looking at the effect of prebiotics on memory in an animal model of Alzheimer's disease in collaboration with pharmacology.

15
00:01:26,160 --> 00:01:30,060
That's still early days yet. And as far as human studies are concerned,

16
00:01:30,060 --> 00:01:38,400
we want to translate the antipsychotic prebiotic study to humans so we can see the effect of prebiotics in schizophrenia,

17
00:01:38,400 --> 00:01:46,170
patients who are taking antipsychotics and we're going to monitor their way to their immune function and so on.

18
00:01:46,170 --> 00:01:53,490
And again, this is all based on studies where we and others have shown that prebiotics affect the immune system,

19
00:01:53,490 --> 00:01:59,550
affect metabolism, makes it more efficient and so on. Another human study we're doing is with children.

20
00:01:59,550 --> 00:02:06,610
We're looking to see if prebiotic administration affects children's learning abilities at school.

21
00:02:06,610 --> 00:02:13,680
And this is really come from animal studies where we've shown precognitive effects of prebiotics.

22
00:02:13,680 --> 00:02:21,630
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?

23
00:02:21,630 --> 00:02:29,940
Do you give the animals the antipsychotic and see what effects it has and then if the prebiotics can reduce that effect?

24
00:02:29,940 --> 00:02:36,640
Yeah, exactly. We inject animals with that. Sarkozy, which is a standard procedure in a drug investigation.

25
00:02:36,640 --> 00:02:39,360
We measure their weight, their behaviour and so on.

26
00:02:39,360 --> 00:02:45,210
And some animals will have an injection and the Previte other animals will have the with the injection of

27
00:02:45,210 --> 00:02:51,540
a placebo or something similar to a party which is known not to have a negative effect on the bacteria.

28
00:02:51,540 --> 00:02:56,400
Can you explain the mechanism behind that prebiotics in their gut bacteria?

29
00:02:56,400 --> 00:03:02,760
Yes, that's a good question. There are a couple of proposed mechanisms which are currently being investigated.

30
00:03:02,760 --> 00:03:08,400
The first is the immune system. It is known to gut bacteria, train our immune system from birth,

31
00:03:08,400 --> 00:03:16,950
and it basically makes us less reactive to inflammation, if you like, and they sort of protect us.

32
00:03:16,950 --> 00:03:19,560
So if we do have an infection,

33
00:03:19,560 --> 00:03:30,720
they help us fight that infection by perhaps outgrowing the pathogenic bacteria or causing the secretion of anti inflammatory molecules.

34
00:03:30,720 --> 00:03:33,840
Now, as we saw earlier last year,

35
00:03:33,840 --> 00:03:41,490
there is a direct connexion between the immune system and the brain is in Nature paper published about this lymphatic system,

36
00:03:41,490 --> 00:03:46,820
which allows these immune molecules and cells into the brain as we and others are

37
00:03:46,820 --> 00:03:50,640
looking at how bacteria modulate the immune system and therefore brain function.

38
00:03:50,640 --> 00:03:54,900
Another method is a gut hormone and the gut bacteria.

39
00:03:54,900 --> 00:04:01,290
When they digest the probiotics, they actually release things called short-change fatty acids,

40
00:04:01,290 --> 00:04:11,810
which stimulate the secretion of gut hormones that tell us to stop eating well before these get hormones also penetrate higher sensitive brain.

41
00:04:11,810 --> 00:04:15,990
And they've been shown to have behavioural effects. So those are the two main effects.

42
00:04:15,990 --> 00:04:24,660
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.

43
00:04:24,660 --> 00:04:31,830
But we're not looking into that other groups. So you've already mentioned the link between the immune system and brain function.

44
00:04:31,830 --> 00:04:38,370
There's a lot of buzz in the literature at the moment about how the immune system is linked specifically to psychiatric symptoms.

45
00:04:38,370 --> 00:04:44,280
Do you think that going forward you could use Prebiotics to modulate, at least in some cases,

46
00:04:44,280 --> 00:04:48,280
psychiatric symptoms as well as the metabolic syndrome and things like that?

47
00:04:48,280 --> 00:04:57,360
Yeah, absolutely. We've already shown in animals that when we challenge them with an detoxing which models bacterial infection,

48
00:04:57,360 --> 00:05:00,990
we see post inflammatory anxiety in these animals.

49
00:05:00,990 --> 00:05:06,510
And the animals had taken the probiotic. For a couple of weeks before we're resistant to this,

50
00:05:06,510 --> 00:05:14,340
so this was really something that was predicted in the reviews of our work, we're quite excited that we've already shown this.

51
00:05:14,340 --> 00:05:16,590
And since then, other groups have shown this as well.

52
00:05:16,590 --> 00:05:24,810
And this sort of ties in with the theory that there are Carpenteria trends or helps or fortifies our immune system.

53
00:05:24,810 --> 00:05:30,870
So, yes, I think if there's a psychiatric disorder with an immune component, then prebiotics would be very helpful.

54
00:05:30,870 --> 00:05:38,430
Yes. Do you think that prebiotics will replace typical psychiatric medications in the future, or at least in some cases, right?

55
00:05:38,430 --> 00:05:44,970
Yes, I always get asked this and my answer always is, in my opinion, absolutely not.

56
00:05:44,970 --> 00:05:49,950
And I don't think they should. Drugs use in psychiatry.

57
00:05:49,950 --> 00:05:54,540
These drugs have their place and a lot of people function well on them.

58
00:05:54,540 --> 00:06:02,230
And I don't think that nutritional substances such as Prebiotics are as powerful as these specific agents.

59
00:06:02,230 --> 00:06:07,050
Now, what they could do, they could help patients respond better to magnification.

60
00:06:07,050 --> 00:06:12,150
So always given with medication. But I don't see them as an alternative.

61
00:06:12,150 --> 00:06:20,020
And I don't think anyone listening who are taking these drugs should you should think they they want to take preventative probiotics.

62
00:06:20,020 --> 00:06:24,810
They should consult their psychiatrist position on treatment.

63
00:06:24,810 --> 00:06:30,020
There's some discussion in the field at the moment about the effect of prebiotics versus probiotics.

64
00:06:30,020 --> 00:06:34,410
So what's your stance? Yeah, that's a good question.

65
00:06:34,410 --> 00:06:41,370
Unfortunately, a head to head comparison prebiotics probiotics has not been made to my stance is on the fence.

66
00:06:41,370 --> 00:06:49,530
I mean, certainly the reason why I was interested in probiotics is because I enhance all the good bacteria in our gut.

67
00:06:49,530 --> 00:06:57,300
Probiotics have specific strains that have been manufactured and you obviously can get now multi strain probiotics.

68
00:06:57,300 --> 00:07:02,520
So you could argue that they might have limited effects because there's fewer stress.

69
00:07:02,520 --> 00:07:05,640
The maximum number of strains I've seen you can buy commercially.

70
00:07:05,640 --> 00:07:12,840
One capsule is about 14, whereas with Prebiotics you are amplifying thousands of different species.

71
00:07:12,840 --> 00:07:17,450
So arguably you could say Primo is better, but there hasn't been.

72
00:07:17,450 --> 00:07:20,130
That has a comparison. So we don't really know.

73
00:07:20,130 --> 00:07:27,600
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.

74
00:07:27,600 --> 00:07:31,520
It's all about the individual says something that is actually upset.

75
00:07:31,520 --> 00:07:42,390
Yeah. What is your academic background and how did it lead you to this area of research in Oxford?

76
00:07:42,390 --> 00:07:47,100
Yes, go back. I'm a biochemist by training. I did obviously in biochemistry.

77
00:07:47,100 --> 00:07:55,500
And I did an M.S. in neuroscience neurochemistry. More specifically, then, I did a Ph.D. in the same area.

78
00:07:55,500 --> 00:08:02,280
But my first postdoctoral post was really about looking at neurotransmitters,

79
00:08:02,280 --> 00:08:08,470
specifically the serotonin neurotransmitter and behaviour, the molecular biology and so on.

80
00:08:08,470 --> 00:08:13,390
And when I came to Oxford, I came to Oxford and a MRC fellowship.

81
00:08:13,390 --> 00:08:17,700
I wanted to look at these neurotransmitters in schizophrenia.

82
00:08:17,700 --> 00:08:24,630
So then I started off looking at serotonin receptors in schizophrenia, post-mortem brain and of course, antipsychotics.

83
00:08:24,630 --> 00:08:34,950
Since coming here in 92, I've been interested in neurotransmitter receptors, schizophrenia and psychotic drug actions there.

84
00:08:34,950 --> 00:08:44,100
What got me into this this microbiome field is that I started to look at the glutamate receptor that's been implicated in schizophrenia,

85
00:08:44,100 --> 00:08:49,140
the NMDA receptor that's proposed to be hyper functioning in schizophrenia.

86
00:08:49,140 --> 00:08:57,060
We've been looking at ways to enhance the function of this receptor, schizophrenia, using animal models and so on.

87
00:08:57,060 --> 00:09:01,560
And one of the ways to do it is to actually directly give a Coalitionist of this receptor.

88
00:09:01,560 --> 00:09:10,120
And one of these coachloads, which is a key amino acid cordiality, is actually a component of the gut bacteria cell.

89
00:09:10,120 --> 00:09:16,590
So all the DNA in our bodies and a little bit in our brain comes from gut bacteria.

90
00:09:16,590 --> 00:09:24,570
So I thought, well, if we augment our gut bacteria, could we also augment the NMDA receptor function?

91
00:09:24,570 --> 00:09:29,700
So I contacted the prebiotic company and we got some money from the PBS to look at this.

92
00:09:29,700 --> 00:09:36,840
And what we found is that certainly prebiotics did have an effect and did have an effect on the NMDA sector, as we hypothesised.

93
00:09:36,840 --> 00:09:43,530
But it actually was nothing to do with the. It was, as I said, probably immune system got warmer.

94
00:09:43,530 --> 00:09:49,440
So so although our prediction let it affects glutamate system in behaviour was correct,

95
00:09:49,440 --> 00:09:55,620
the media data is absolutely wrong because we were halfway there.

96
00:09:55,620 --> 00:10:07,250
So so that's what really got me into this field is the link with schizophrenia and empty receptors.

97
00:10:07,250 --> 00:10:11,640
Is there anything that you've had to overcome to get to where you are today?

98
00:10:11,640 --> 00:10:23,960
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.

99
00:10:23,960 --> 00:10:28,440
You've certainly come quite a long way. So is it just a case of perseverance?

100
00:10:28,440 --> 00:10:35,980
I think perseverance.

101
00:10:35,980 --> 00:10:45,250
We've had a new idea where we ask budding academic psychiatrists and psychiatric researchers to ask questions to our professors about their work.

102
00:10:45,250 --> 00:10:48,700
So we've had a question from Thomas who says,

103
00:10:48,700 --> 00:10:55,270
I'm very concerned about the number of pathogens that can be detected or involved in the microbiota of people with mental disorders.

104
00:10:55,270 --> 00:10:59,410
There are a lot of genes in the genome. There are also a lot of organisms in the microbiology.

105
00:10:59,410 --> 00:11:02,230
This could lead in the same way to a false positive.

106
00:11:02,230 --> 00:11:07,660
The way to avoid that could be to make a very large study with very low statistical significance threshold.

107
00:11:07,660 --> 00:11:13,040
Is there any organisation or consortium in this topic that could coordinate such a study?

108
00:11:13,040 --> 00:11:16,750
That's a good question. The answer is yes. The short answer is yes.

109
00:11:16,750 --> 00:11:25,720
There's actually the Human Microbiome Project, which started in 2008 at the National Institutes of Health in the USA,

110
00:11:25,720 --> 00:11:31,160
and the aim was to sequence the whole human microbiome in health and disease.

111
00:11:31,160 --> 00:11:41,140
This this facility allows researchers quite a few now on the microbiota to deposit their data about the microbiome and disease.

112
00:11:41,140 --> 00:11:48,910
So if Thomas goes to the website, you see the workshops, there's information about this, and it's exactly to address that question.

113
00:11:48,910 --> 00:11:53,650
So I think quite soon, perhaps, and perhaps in 10 years or so,

114
00:11:53,650 --> 00:11:59,650
there will be information out there about severe psychiatric diseases and microbiome composition.

115
00:11:59,650 --> 00:12:03,220
OK, that's great. Thank you very much for speaking to us today as a pleasure.

116
00:12:03,220 --> 00:12:11,376
Thank you.