YT YouTube2Text

YouTube2Text → Transcripts → The Gut–Brain Axis: Hype or Clinical Reality?

The Gut–Brain Axis: Hype or Clinical Reality? — Transcript

by Yakult UK & Ireland · 10,387 words · 1,684 segments · language en · Watch on YouTube

Open in transcriber Summarize with AI Download SRT/VTT

Full transcript

0:00A big welcome to our fifth and final
0:03webinar in our series got educated with
0:05Yakult Science. A big welcome to you all
0:08whether this is your first webinar of
0:09ours that you are joining or whether
0:11you've joined some of our previous
0:12webinars, you are very very welcome and
0:14I can confirm that you're absolutely in
0:16for a treat this lunchtime. We're really
0:18really excited to hear from Professor
0:20Swan. So first of all for the those of
0:22you who maybe aren't familiar with
0:24Yakult Science or the team, I just
0:26wanted to share a little bit about what
0:28we offer here at Yakult Science for
0:30Health.
0:31So my name is Dr. Holly Neil and I'm the
0:33Science Manager for Yakult UK and
0:35Ireland and within Yakult Science for
0:37Health, we are really a education hub
0:39for healthcare professionals,
0:41researchers and students to educate and
0:43empower on all things related to the gut
0:46microbiome. With that in mind, we create
0:48lots of resources in-house on various
0:50different topics including the gut-brain
0:52axis, gut-immune axis,
0:55female gut microbiome, gut metabolism.
0:57There's loads and loads of different
0:58resources on our website in various
1:00different booklet format that you can
1:02download for free or feel free to get in
1:04touch with the science team and we're
1:05more than happy to send hard copies for
1:07free.
1:08We also put on a various events so like
1:10today's webinar, we do online events and
1:12then we also host in-person events in
1:14London as well.
1:16We offer free workplace talks so often
1:18we'll go to GP practices or hospitals
1:20and share the latest research
1:22surrounding the gut microbiome,
1:23probiotics and whether there's a
1:25particular topic of interest. We also
1:27give out free money which is great news
1:29to people. So we have our educational
1:31grant and we run this twice a year. So
1:34the next deadline is the end of
1:36September and we give away a thousand
1:38pounds or a thousand euros to two either
1:40healthcare professionals, researchers,
1:42students. And that grant is really to
1:44help fund your attendance at a
1:46conference or to join a training
1:48program. So if you're interested in
1:50that, check out our website and do fill
1:52in the application form before the next
1:54closing date.
1:55We also have a podcast called Microbiome
1:57Matters and this is available on Spotify
1:59and Apple Podcast. And then lastly,
2:01globally as a company, we're very
2:03actively involved within research. And
2:05then particularly considering the local
2:07team, we're currently partnering with
2:09King's College London on a randomized
2:11control trial looking at the gut-skin
2:13axis. So, if you want to learn more
2:15about us or access any of those
2:17resources or the grant application form,
2:19then please do scan the QR code on your
2:21screen now, and that will take you
2:23through to our website.
2:25We're also really active on social media
2:27on both LinkedIn and Instagram. So, if
2:29you don't already follow us, please do
2:32uh give us a like and a follow. We
2:33really really love to see our follower
2:35uh count increase, and it's one of the
2:36best ways to stay up-to-date with any
2:38activities or any events uh that we're
2:41joining or any new resources. And
2:42obviously during today's webinar, we
2:44would love for you to post about it uh
2:46whether that's on your Instagram stories
2:47or to do a summary on LinkedIn
2:49afterwards. It's always really
2:50encouraging both for ourselves, but also
2:52really for our speaker for them to see
2:54what you've taken away from the webinar.
2:56So, yeah, please do feel free to tag and
2:59share all your learnings uh from today's
3:01session.
3:03Now, at the end of each webinar, we
3:05always ask people, you know, is there
3:06any topic that you want to hear about?
3:08And gut-brain axis has came up time and
3:12time again. So, we decided, let's give
3:14the people what they want. So, we're
3:16really excited to have an absolute
3:18expert in Professor Jonathan Swann join
3:20us today. So, Jonathan Swann is a
3:22Professor of Biomolecular Medicine in
3:24the School of Human Development and
3:26Health, Faculty of Medicine at the
3:28University of Southampton. And he's also
3:30a Visiting Professor at Imperial College
3:32London. He leads a research program
3:34studying the metabolic interactions
3:36between the human host and their
3:38microbial partners and their
3:39implications for development, disease,
3:41and health.
3:42He has a specific interest in the
3:44microbiota and gut-brain axis and is
3:46director of the UK Gut Immunology Brain
3:49Axis Network. I'm sure many of you will
3:51be familiar with that. He's also led
3:53several projects in this area funded by
3:55international research councils,
3:57charities, and industry partners, and
3:59his work has been published in
4:00world-class, high-impact journals, and
4:02he's an associate editor for the
4:03journals microbiome and biofilms and
4:06microbiome. So, an absolute expert in
4:08the field. So, I'm absolutely delighted
4:10to welcome Jonathan um to the virtual
4:12stage. Um Jonathan, yeah, thank you so
4:15much uh for your time in joining us
4:17today. I know that yeah, we're all going
4:18to benefit a lot from it. So, I'm going
4:20to stop yapping. I'm going to turn off
4:21my camera and my mic um and I'll pass
4:23over to uh you to take over.
4:26>> Great. Thank you for the invitation to
4:27speak today and the lovely introduction.
4:30So, there we go. I've got my pointer
4:31going. Yes, so yeah, good afternoon
4:33everyone. Uh today I'm going to talk
4:34about the gut-brain axis, hype or
4:36clinical reality, and hopefully I'll
4:38convince you that it's a clinical
4:39reality. Uh so,
4:42just to get started then, um
4:45we probably well, we've known for a long
4:46time of what everyone would probably get
4:48on board with the idea that our brain
4:50can influence our guts. You think about
4:52when you're nervous or anxious, and you
4:54get those what we refer to as
4:55butterflies in our stomach. Clear
4:57illustration of how our brain can
4:59control the environment in the gut.
5:02But, we're increasingly understanding
5:03now how the gut can also control the
5:06brain. This is a two-way communication.
5:08And when we talk about the gut, we're
5:10not just talking about the human cells,
5:12the host cells. We're actually talking
5:14about the trillions of microorganisms
5:16that live there as well, what we refer
5:18to as the gut microbiota,
5:20uh and how these can communicate with
5:21the brain and influence um things like
5:24behaviors, development.
5:26I wasn't entirely sure of the audience
5:29today. So, just a very quick
5:30introduction to what the microbiota is.
5:32So, when we use terms like microbiota,
5:35we're referring to like the the sets of
5:37microorganisms within a particular
5:39niche. Uh and so, your body is colonized
5:42inside and out by a huge array of
5:44microorganisms, but the main ones we
5:46focus on the bacteria, the viruses, and
5:48fungi. This can also include things like
5:50protozoa, and we also put the worms in
5:52there as well.
5:53And so, you have, depending on different
5:56environmental pressures, this can create
5:58these different niches around the body.
6:00So, you have things like an oral
6:01microbiome, a lung microbiome, a skin
6:03microbiome, and the best studied and the
6:06most abundant in numbers is the gut
6:08microbiome. And when we talk about the
6:10gut microbiome or gut microbiota, we're
6:12really referring to or usually referring
6:15to the bulk that are in the colon, the
6:17large intestine.
6:19And a really important point, I'll I'll
6:21try to hammer this throughout this talk,
6:22is that everyone has a unique signature.
6:25You've got a unique microbiome. So,
6:27everyone on this call, you've got a
6:28composition of your microbiome that's
6:30unique to you. And that's because it's
6:32driven by intrinsic factors, like your
6:35genetics, your gene expression, your
6:37immune system, but it's also shaped by
6:40the environment as well. So, what you
6:42eat, things like pollution you're
6:43exposed to, psychosocial stress,
6:47um who you live with, whether you've got
6:49animal pets, this can all impact on the
6:51microbiome, and it results in you having
6:53a very unique one to you and to your
6:55system.
6:58And really,
7:00we've sort of started Well, we've
7:01understood for a long time that this
7:03this influence of the gut microbiome on
7:05host health isn't just restricted to the
7:07gut. It actually expands throughout our
7:09body and can impact on peripheral organs
7:12as well, and it's been implicated in
7:14both health, but also various disease
7:16states as well. It's been linked in with
7:18things like cancers, heart disease,
7:20liver disease, kidney issues, diabetes,
7:23metabolic disease, respiratory disease.
7:25And really, what I'm going to focus on
7:27today is its impact on the brain.
7:33And probably even the last two decades,
7:35last 20 years, we've we've really
7:37started to understand more and more
7:38quite quickly about what we refer to as
7:40this microbiota gut-brain axis. Um and
7:44the sort of mechanisms through which the
7:46microbes influence the brain and what
7:49the implications are for this. And we've
7:50we've
7:51sort of understood this across the life
7:53course and that you've got these these
7:54interactions between the genome and the
7:57microbiome throughout life and those
7:59relationships are changing and they have
8:01implications for things like health
8:03aspects from things like
8:04neurodevelopment, things like appetite,
8:06feeding behaviors, memory and learning,
8:09but they can also have adverse impacts
8:11on aspects such as mental health,
8:12anxiety, depression, schizophrenia,
8:15dementia, ADHD, autism spectrum
8:18disorders. And so the the implications
8:21we're seeing are evolving all the time.
8:25And so the mechanisms through which the
8:27microbes are
8:29talking or communicating to the brains,
8:31so like I say, these are bidirectional
8:32communications. It goes both way, but we
8:34believe that there are three main uh
8:37pathways. Well, first of all, we have
8:38the immune pathway. So, this can be the
8:40microbes can interact with the immune
8:42system in the gut, which can relay
8:44signals to the brain. There's occasions
8:46where the microbes can leave the gut and
8:48reach the brain where they can provoke a
8:51uh a neuroinflammation. They activate
8:53the immune system of the brain. There's
8:55also the nervous pathway.
8:57And this particularly involves the vagus
8:59nerve. Um so, the vagus nerve extends
9:01from the brain to the gut and around 20%
9:04of those signals go from the brain to
9:06the gut where the brain can control gut
9:08processes. We now know that about 80% of
9:11those signals actually go the other way
9:13and actually the vagus nerve is it
9:15provides this this route for very rapid
9:17communication. So, these signals are
9:19transmitted on the the millisecond
9:21scale. So, this allows a very quick
9:23route and it's thought that the vagus
9:25nerve is allows the brain to constantly
9:27sense what's going on in the gut and
9:29allows microbes to send brain messages
9:31to the brain very quickly. And then
9:34probably the bulk of what I'll talk
9:35about today is the biochemical pathway
9:37and this is what a lot of my research is
9:38focused on and this idea that how the
9:41metabolites that are produced by the
9:43microorganisms can have an effect on the
9:45brain whether that's acting locally in
9:47the gut impacting on the vagus nerve or
9:50whether their metabolites that directly
9:51reach the brain to have their effect.
9:53And through various studies we've found
9:55a whole range of different metabolite
9:57classes involved in this communication.
10:02And then so one of the reasons why this
10:03is this is so important is the the
10:06breadth of metabolites that can be
10:08produced by the microorganisms. So just
10:10to start from the beginning
10:12as I said that the body's colonized
10:14inside and out and and the current
10:16estimate is that we have about 39
10:17trillion microbial cells in and on our
10:20body.
10:21And if we focus specifically on those in
10:23the gut and particularly the bacterial
10:24cells, an important point to make here
10:27is that for each individual bacterial
10:29cell there is an accompanying genome
10:32that contains genes. And so different
10:35bacterial cells, different species,
10:37different strains of which there are
10:38hundreds, thousands,
10:39different bacterial species and strains
10:41bring with them different genomes which
10:43contain different genes. And if we think
10:45about these trillions of genomes
10:47collectively, what's often termed the
10:49metagenome or the gut metagenome
10:52it's been estimated that it contains
10:55around 3 million different microbial
10:57genes.
10:58So when you compare that to your human
11:00genome which is around 24,000 genes, you
11:03can start to appreciate there's there's
11:04anywhere from 100 to 150 times more
11:07genetic information in your metagenome
11:10than in your human genome. And many of
11:12these genes will encode enzymes that can
11:15perform metabolic functions.
11:17And hopefully you can start to
11:18appreciate that a lot of these
11:20biochemical functions coming from the
11:22metagenome, they're not present in our
11:24genome. So what the microbiome does is
11:27it extends our metabolic capabilities.
11:29Our the the sorts of uh
11:32we can perform is contributed by the
11:34microbiome. That expands the diversity
11:37of molecules we can break down, usually
11:39coming from the diet, but it also
11:40increases that array of molecules that
11:43we're exposed to.
11:44And a lot of these microbial metabolites
11:46can impact on both health and disease.
11:49And that's kind of what we're really
11:50interested in studying here, how these
11:52metabolites produced by the microbes can
11:55impact on on host health.
11:59And I'll also say these these effects of
12:01the microbiome aren't just restricted to
12:04the gut. And actually this was a study
12:06we did over 10 years ago now, where so
12:09this is looking at short-chain fatty
12:10acids
12:12uh
12:12that are tend to be associated with
12:14beneficial effects of the microbiome.
12:16They come from carbohydrate
12:17fermentation, can also come from amino
12:19acid fermentation.
12:21Um and one of these short-chain fatty
12:23acids, acetate, we demonstrated here
12:25that if you carbon-11 label acetate and
12:27directly inject it into a mouse's gut,
12:30about 3 to 5% of that dose ends up in
12:33the brain. So it shows you that a
12:34metabolite produced in the gut can
12:36migrate to the brain where it can have
12:38an effect. And actually these
12:39short-chain fatty acids are really
12:41interesting. They've been shown in the
12:42gut they can stimulate enterochromaffin
12:45cells to release neurotransmitters, and
12:47they can also stimulate enteroendocrine
12:49cells in the gut to release these
12:51appetite hormones GLP-1 and PYY, which
12:54can then go and increase things like
12:55satiety, which that feeling of fullness,
12:58they reduce appetite. And it's through
13:00these metabolites has been shown that
13:02the microbiome can influence things like
13:04feeding behaviors and appetite.
13:08And so there's a whole range of
13:09different impacts then that the
13:11microbiota can have on the gut-brain
13:12axis, which can impact on on health and
13:14disease. So some examples being studied
13:17currently are things like eating
13:19disorders, neurodevelopmental disorders,
13:21neurodegeneration, addiction,
13:23dysfunctional neuronal activity,
13:25stress-related disorders. And I'll go
13:26through a few of these today. Obviously,
13:28um
13:29not got too long to talk, so I'll try
13:30and just pick a few examples.
13:33So, in terms of emotional behavior,
13:36this was one of the first studies really
13:38that showed this this influence of the
13:41microbiota on the gut-brain axis.
13:44Um and so, this was back in 2011, and it
13:46was looking at behavior and emotional
13:48behavior, in particular anxiety.
13:51And the one of the ways you can study
13:52this is you can get germ-free animals.
13:56So, germ-free animals are born and
13:57raised in sterile conditions, so they
14:00actually don't have any exposure or
14:02don't harbor any microorganisms. They're
14:04completely devoid of a microbiota. And
14:07you can compare these to standard lab
14:09animals that have a microbiome.
14:12And so, it's like a knockout. You can
14:13compare with a microbiome to without a
14:14microbiome.
14:16And in this test, this is the open field
14:18test. It's like a big white box.
14:20And the mouse is put in the box, and you
14:23look at how much they're willing to
14:24explore, so locomotor activity. And you
14:28can see And so, the idea is if they
14:29explore more, they have lower anxiety.
14:32But if they spend a lot more time near
14:34the sides of the walls, then they sort
14:36of evidence of higher anxiety-like
14:38behavior. And if they don't spend much
14:39time in the middle, that's also lower
14:41anxiety behavior.
14:42And what you can see when you've got a
14:43microbiome, the mice spend the first 10
14:45minutes with a lot of locomotion
14:47activity, but that that dwindles over
14:49time. They don't spend much time in the
14:50middle. Whereas in the germ-free state,
14:52when you haven't got a microbiome, they
14:54spend a lot more time exploring, a lot
14:56more crosses over the middle. So, this
14:59was found to be demonstration that if
15:01you take the microbiome away, actually
15:03they have lower anxiety-like behavior in
15:05these animals.
15:08Another test for this is the elevated
15:09plus maze, like a giant plus that's
15:11raised off the ground, but two of the
15:13arms are what you call closed. They've
15:15got sides around them.
15:17And two of the arms are open. The idea
15:19is if the animal is more anxious,
15:21they'll spend more time in the closed
15:22arms, whereas if they're less anxious,
15:24they'll spend more time in the open arms
15:26and particularly at the end. And what
15:28you can see here, this is consistent
15:29with the first test, that the germ-free
15:31animals, when you haven't got a
15:32microbiome, they spend significantly
15:34more time in the open arms and
15:35particularly at the ends of those arms.
15:38Again, consistent that those
15:40microbiota, you take them away, they
15:42have lower anxiety-like behavior.
15:45What was really interesting in this
15:46study is what the investigators found is
15:49you can take germ-free animals and put
15:51them in a a cage with normal lab animals
15:54and they start to colonize. Their guts
15:56become colonized with with the
15:58microbiota, they establish a microbiota.
16:01And what they demonstrated is actually,
16:03if you took the germ-free animals and
16:04recolonized them before 6 weeks of life,
16:07then these behavioral differences
16:09disappeared. You no longer saw these
16:11behavioral differences. But if you tried
16:13recolonizing them after 6 weeks,
16:16these differences persisted. So, it
16:18shows there's this developmental window
16:21for developmental programming where the
16:23microbiome can have its influence, but
16:24after that period, it you can't change
16:27it.
16:29And this leads us on to the impact of
16:31the microbiome and the gut-brain axis in
16:32early life. And this is where my group
16:34kind of does a lot of research in. And
16:36that's because the majority of human
16:38brain development happens in the first 2
16:41years of life.
16:43And that's a really important period of
16:44when you acquire your microbiome.
16:47Uh and that's because the current
16:49hypothesis is you're born sterile at
16:51birth and then you rapidly acquire the
16:53microbes and that can be influenced by
16:56uh feeding uh yeah, feeding patterns
16:58like breast milk, formula milk, delivery
17:00type, whether C-section or vaginal
17:02birth, whether we're exposed to
17:03antibiotics, time of weaning. This can
17:06all shape the colonization trajectory of
17:08the microbiome.
17:10And what we're interested in, because
17:12brain development happens at the same
17:13time, how does a subtle change or
17:15pronounced change in those colonization
17:17trajectory, how does that imprint on
17:19brain development?
17:22And actually data now is suggesting that
17:24we probably even need to think earlier
17:25than that. There's also some evidence
17:27now that maternal microbiome during
17:29pregnancy can also influence
17:31neurodevelopment in the offspring.
17:33And so this was some work by Elaine
17:35Hsiao's group about six years ago now
17:37using germ-free animals and
17:39antibiotic-treated animals showing that
17:41actually the mom's microbiome by
17:43producing those metabolites, those
17:46metabolites can cross the placenta and
17:48actually influence fetal brain
17:50development. And it was shown that some
17:52specific examples like trimethylamine
17:54N-oxide or TMAO that people might have
17:56heard about, TMAO can actually promote
17:59axonogenesis and help contribute to
18:01neurodevelopment in mice. So this is
18:03where you kind of reintroduced that
18:04concept of having that unique
18:06microbiome. If you're a mom that's
18:08strongly enriched with microbes that
18:10produce that TMAO, the fetus could be
18:12exposed to higher amounts of TMAO than a
18:14mom whose microbiome is not enriched for
18:17producing things like that TMAO.
18:20And then that was largely mouse data.
18:22And so in terms of humans, there are
18:24some some studies. So this was one study
18:28looking at the stool microbiota. So it's
18:31thought that the stool the the
18:33microorganisms in the stool is a good
18:35reflection, a good proxy for studying
18:37the microorganisms in the colon. And so
18:39by comparing those stool microbes from
18:42healthy controls to those with major
18:44depressive disorders, you can see if
18:46there's a microbial signature of
18:48depression. And actually there were some
18:50quite clear differences in the microbes
18:52present.
18:53And then this was some work by Mariah
18:55Valdes Colonus um
18:57lab showing that actually this was this
19:00was a very large study looking at
19:01thousands of of of individuals and
19:04looking at those metagenomes and looking
19:06if there any components in the
19:07metagenome associated with depressive
19:09symptoms or quality of life. And here
19:11they saw some quite clear differences
19:14associated with depression. In fact, it
19:16was seen that those short-chain fatty
19:18acids we spoke about earlier, they are
19:20particularly low in or or the potential
19:22to produce those short-chain fatty acids
19:24are low in individuals living with
19:25depression there.
19:27But, and this is a common
19:29uh comment about the field, these are
19:30association studies. We can't say for
19:32sure if these microorganisms are driving
19:35depression or whether the depression is
19:37actually driving the changes in the
19:39microbiome. For example, we know that
19:41stress can change the gut environment,
19:43that can change the microorganisms.
19:45Plus, we know that often when people are
19:47suffering from depressive symptoms, they
19:49change their eating habits, which can
19:52also change the microbiome. So,
19:54establishing causality is a real sort of
19:56pressure in the field.
19:59And that was kind of addressed in this
20:00study. This was uh sort of major study
20:02that helped to advance the field. So,
20:04this is by Ted Dinan's group, John
20:06Cryan, and Gerard Clarke's group over in
20:07Cork.
20:09And here what they demonstrated is they
20:11could take rats, treat them with
20:13antibiotics for 4 weeks to sort of
20:15cleanse the gut, and then take fecal
20:18samples from healthy control peoples or
20:21or um people with depressive symptoms
20:24and transplant transplant or transfer
20:26those into the rats, allow the
20:28microorganisms to establish, and then
20:30did a range of behavioral tests.
20:33And what you can see here, so if we go
20:35back to that open field test, that's
20:36that big white box. Can you remember
20:38that time in the middle was
20:40uh a sort of measure of how sort of
20:41anxiety levels. And you can see that the
20:44the rats receiving the depressive
20:46microbiota,
20:48they actually spent significantly less
20:49time in the center of that open field
20:51test, indicating increased anxiety-like
20:54behavior.
20:56Also, in the elevated plus maze, those
20:58receiving the depressed microorganisms
21:00also spent significantly less time in
21:02the open arms, again consistent with
21:04higher anxiety-like behavior.
21:06And then a more specific test for
21:08depression, this is a a test of
21:10anhedonia, which is the loss of interest
21:12in things you would normally be
21:13interested in, which is a common feature
21:15of of depression. A way you can test
21:17this in rats is they quite like sweet
21:19things.
21:20And so you can put a bottle of water in
21:22the cage which is normal water and a
21:24bottle of water in the cage with sugar
21:27in it and you can see if they have an
21:28increased preference to the sugar water.
21:31And that's what you can see here in the
21:33rats receiving the healthy control
21:35microbiota,
21:37um they spend about 80% of their time
21:39with the sucrose, with the sugar water,
21:41but with the depressed microbiota, they
21:43actually have a a lower preference for
21:45that sweet sugar water.
21:47So what this demonstrates for the first
21:49time is you can actually transfer
21:51emotional behavior by transferring the
21:54microbiota and it helped to move us that
21:56step closer to establishing causality.
22:01So they were through microbial um
22:03metabolite outputs. Um another way
22:05through which the microbes can influence
22:07the brain is through uh inflammation and
22:10through interactions with the immune
22:11system.
22:13So in a healthy gut state, you have a
22:15nice diverse microbiome with probiotics
22:18present. They produce short-chain fatty
22:20acids which help to promote these what
22:23we call tight junction proteins which
22:25sit between cells and this creates quite
22:27a nice tight barrier and so you have a
22:29lot of control over what moves from the
22:31gut into the circulation.
22:33But as we move to a more aberrant
22:36microbiomes such as when people age,
22:38their microbiome becomes lower diversity
22:41and the short-chain fatty acid
22:43production tends to decrease and
22:46what you also see is an increased
22:47production like lower carbohydrate
22:50fermentation and instead an increased
22:51amino acid fermentation and and
22:53metabolism. And that can produce harmful
22:56molecules like paracresol or phenols.
23:00And these have actually been shown to
23:01disrupt this barrier. In fact, we
23:03demonstrated that here in this study.
23:05This was looking at 1,000 people from
23:06Taiwan and 1,000 from America. And we
23:08see as people get older, their
23:10microbiome produces more of these more
23:12harmful metabolites, which can impair
23:14gut function. And so as a result, you
23:17lose this control of of keeping the
23:19microbes in the gut. And instead, the
23:21microbes can translocate. They can move
23:24from the gut into the circulation. And
23:26it's here they can trigger systemic
23:29inflammation, but they can also reach
23:31the brain and drive neuroinflammation.
23:33And this can be because largely the
23:35gram-negative bacteria have this
23:37component on their outer cell wall
23:39called lipopolysaccharide or LPS. And
23:41like I said, it's a potent inflammogen.
23:43It drives this inflammation.
23:47Now, the how this can impact on
23:49behavior, well, inflammation can be
23:51good. It's the body's way of kind of
23:53clearing infections, but sustained and
23:55chronic inflammation is bad. And so as a
23:57result, the body has this mechanism to
24:00try to dampen that inflammation. So when
24:03inflammation is detected, this enzyme
24:06IDO, indoleamine dioxygenase, gets
24:08activated or induced. And this catalyzes
24:12the breakdown of tryptophan to
24:13kynurenine.
24:14And then kynurenine gets further broken
24:16down to something called anthranilic
24:17acid. And these these metabolites help
24:20drive, they push
24:22naive T cells away from becoming
24:25inflammatory TH17 into more tolerogenic,
24:28more tolerant T reg cells. So this, when
24:31inflammation is detected, this is
24:33switched on. Tryptophan is converted to
24:34kynurenine. And that that sort of
24:36signals to the immune system to become
24:38less inflammatory and more tolerant.
24:41And so that's good cuz it dampens that
24:42inflammation, but it's bad because what
24:44this does is it pulls tryptophan to
24:46kynurenine and less becomes available to
24:49serotonin. This is often what's referred
24:50to as the tryptophan steal. So there's
24:53less availability of tryptophan for
24:54making serotonin. IDO can also break
24:57down serotonin, so this reduces the
25:00overall amounts of serotonin, which can
25:02impact on depressive-like behavior.
25:04And then also this kynurenine can get
25:06further metabolized into quinolinic
25:09acid, which is a a neurotoxin. It's
25:11actually associated with things like
25:12sickness behavior you get when you have
25:14a common cold.
25:16And so these things combined are really
25:17nice illustration of how the microbiota
25:19trigger the immune system, which alters
25:22this biochemical system, which impacts
25:23on behavior.
25:27And actually this quinolinic acid is
25:28more recently been associated with brain
25:30fog in people with coronavirus.
25:34Um so yeah, it's been associated with
25:35brain fog and we're seeing increasing
25:37links with this.
25:39Uh and then in addition, we're also
25:40seeing that this pathway, this
25:41tryptophan pathway, is also disrupted in
25:44Alzheimer's disease. Uh so this was a
25:46study we did in in humans um a few years
25:49ago
25:50where we observed that the all of these
25:52metabolites were reduced in individuals
25:55with Alzheimer's disease either in urine
25:56or serum. And what you can also look is
25:58you can take the kynurenine over
26:00tryptophan ratio as a measure of that
26:03IDO induction, and we consistently see
26:05that people with Alzheimer's disease
26:07have a higher KT ratio, a higher IDO
26:09induction.
26:11And so it's thought that through the
26:12microbiota influencing the inflammation
26:15could be contributing to the progression
26:17of Alzheimer's disease, and there's
26:18quite a lot of research going on in that
26:20area.
26:22And that leads us on then to cognition.
26:25And again, this is one of the early
26:27studies uh looking at the gut-brain
26:29axis. And again, using germ-free mice
26:32and specific pathogen-free mice. And
26:34this time it was using the novel object
26:36test to look at memory formation.
26:38And how this test works, so the mice are
26:40put in a cage with two objects.
26:43And they're naturally quite inquisitive,
26:45so they'll sniff and smell and explore
26:47these two objects.
26:48And then you can have a testing day
26:50where one of the objects is removed and
26:52a new or novel object is introduced.
26:56And the idea is if the animals have
26:57memory, they'll remember that they've
26:59already explored this object and they'll
27:01spend more time exploring the novel
27:03object.
27:04And that's what you can see here when
27:06you've got a microbiome present, the
27:07white bars, they spend about 70% of
27:10their time exploring the new object
27:11showing they've got memory. But in the
27:13germ-free state, you remember the
27:15germ-free animals were less anxious, but
27:17here now it seems that they actually
27:19have an inability to form memories. They
27:21actually spend 50% of their time with
27:23the new object, 50% of their time with
27:25the old object. So, taking the
27:27microbiome away actually impacts on the
27:29ability to form memories.
27:33And so we're exploring ways through
27:35which this might be mediated. And one of
27:37the areas we're particularly interested
27:38on are the bile acids. Now, bile acids
27:41are often what we call microbial host
27:44co-metabolites. They come from the
27:45combined metabolism of both the
27:48microbiome and the host. We also refer
27:50to these as transgenomic as they come
27:52from the genome and the metagenome.
27:55And so how they're formed, so
27:56cholesterol in the liver is used to make
27:58what we call primary bile acids, which
28:00are then conjugated with glycine or
28:02taurine. This helps put them into the
28:03bile. Then when you consume a meal, that
28:05bile is released into the gut where it
28:08helps to break down and digest and
28:09absorb fats, the lipids.
28:13And around 95% are reabsorbed in the
28:15small intestine and recycled back to the
28:17liver, but around 5% make it to the
28:20colon. And it's there in the colon that
28:22the bacteria will act on them. First of
28:24all, they'll deconjugate them. They'll
28:26take off that glycine or taurine, and
28:28then they'll convert them further,
28:29dehydroxylate or epimerize them,
28:31converting them from primary bile acids
28:33into secondary bile acids.
28:36These are then either lost in the stool
28:37or reabsorbed and returned to the liver
28:39where they're then reconjugated and put
28:41back in the bile.
28:43And again, going back to this idea of
28:45having a unique signature, differences
28:47in your microbiome result in differences
28:50in your bile acids present. And we
28:51actually showed this here that the
28:52microbiome has a strong influence on the
28:54variety of bile acids circulating in
28:56your bile acid pool.
28:58And this is important because bile acids
28:59aren't just necessary for digesting
29:02fats.
29:03We actually know now that these bile
29:05acids combined to different receptors
29:07expressed throughout the body. And when
29:09these bile acids bind to these
29:11receptors, they change gene expression
29:13in things like metabolic pathways. So,
29:15we know they can impact on glucose,
29:17lipid, energy metabolism. Can also
29:19impact on drug metabolism. It can also
29:22impact on immune inflammatory responses
29:24as well. And we know that different bile
29:26acids have different potencies for these
29:29receptors. So, changes in your
29:31microbiome result in changes in your
29:33bile acid pool, which result in changes
29:35in their signaling potential.
29:37And I'm talking about this because we
29:39also know now that the bile acids can
29:41have a role in the gut-brain axis.
29:43We know that bile acids can be detected
29:45in the brain, that the brain has
29:47receptors and transporters for bile
29:49acids. And these individuals
29:51demonstrated that if you knock out FXR,
29:54which one of the main bile acid
29:55receptors in mice, if you knock this
29:57out, then it actually changes the
29:59behavior of mice. They have lower
30:01depression and anxiety-like behavior.
30:03They have impaired memory and reduced
30:05motor coordination. And it also changed
30:07a whole variety of neurotransmitters as
30:09well. So, the bile acids can signal to
30:12the brain through things like these
30:14receptors.
30:17And actually some more recent work we've
30:18done, so this is currently unpublished,
30:20where we've looked at a thousand people
30:22from Spain.
30:24And we've measured the bile acids in
30:26their blood. Now, these people are aged
30:27between 50 and 90.
30:30And what we see is that the older people
30:31are, naturally, they perform worse on on
30:34cognitive tests. And this is quite
30:36common. This is what we call normal
30:38age-related cognitive decline.
30:40But what we found is when we measured
30:42these plasma bile acids, we actually
30:44found some bile acids associated with
30:46cognitive ability. And in particular, we
30:48found that this one bile acid,
30:50hyodeoxycholic acid or HDCA, was
30:53significantly inversely associated with
30:56cognition. So the people that performed
30:58worse on the cognitive scores had higher
31:00amounts of this bile acid. It was
31:02anti-cognitive.
31:03And this is after adjusting for things
31:05like BMI and sex and age.
31:09So this is an anti-cognitive bile acid.
31:12To sort of explore this and test
31:14causality, we then took fecal samples
31:17from people that had high amounts of
31:19HDCA in their blood. So we hypothesized
31:22that their microbiome would be producing
31:23high amounts of this bile acid. And then
31:25we took feces from people with no HDCA
31:28in their blood. So their microbiome
31:30couldn't produce it. And we transplanted
31:32these into mice.
31:34And we then did the Morris water maze
31:35test. So here the animals put in a bath
31:37of water and they're swimming to find a
31:39platform. And over time they learn where
31:41the platform is. And the idea is the
31:43better their spatial reference memory,
31:46the
31:47shorter their path lengths and the more
31:50efficient their path lengths. And what
31:52you can see here, so that the mice
31:54receiving the HDCA producing microbes
31:57actually had longer path lengths.
32:00With a less efficient. So it confirms
32:02what we see in adults. We can transfer
32:04this cognitive ability through
32:06transferring these microorganisms.
32:08But one
32:10point here could be that the HDCA is
32:12just a marker for having a microbiome
32:15that impacts on cognition. So what we
32:18did next is we took mice and we directly
32:21fed them, well, we gavaged them with
32:22this HDCA. We directly gave them just
32:25the bile acid.
32:26And we did the Y maze test. So here the
32:28animals are put at the start of the Y
32:30maze. They'll go left or right. Then you
32:33can pick them up and start them again.
32:34If If got memory, they will alternate
32:36and go to a different or a novel arm.
32:39What you can see, those receiving the
32:41anti-cognitive bile acid spend
32:43significantly less time going to the
32:45novel arm and actually more time staying
32:47at the start of the test.
32:50Sort of reinforcing that effect that the
32:51HDCA could be contributing to this.
32:54We showed that when you give the HDCA
32:57when we gavaged the mice, you actually
32:58increase the amount in their blood
33:00and also you increase the amount in the
33:02prefrontal cortex, so it can actually
33:04reach the brain. And actually in the
33:06brain we found that giving the HDCA
33:08actually significantly reduced the
33:10expression of these important receptors
33:12for bile acids, FXR and TGR5.
33:15And our current hypothesis is that this
33:16is probably acting on dopamine synthesis
33:19and transport, which is key for for
33:21learning and memory.
33:24And just the last kind of example I'll
33:26go to is conditions associated with the
33:29gut microbiota and in particular autism
33:31spectrum disorders.
33:33The current hypothesis is that
33:35autism spectrum disorders are are driven
33:38by
33:39a genetic predisposition that relies on
33:42an environmental trigger, of which the
33:45microbiome might be one such trigger.
33:47Now now to explore this, so one of the
33:50main risk factors for autism spectrum
33:52disorders are having an older sibling
33:54with ASD in the family. And they have a
33:5620% increased genetic risk. So this was
33:58a study led by Rochelle Diaz Heights at
34:01the Karolinska.
34:02And here infants were recruited that
34:04either had a sibling with ASD in the
34:06family already, this was the elevated
34:08likelihood group. They were recruited at
34:09birth. And those with a neurotypical
34:12sibling, these are the low likelihood
34:13group.
34:15And then they were followed for 3 years
34:17and stool samples were collected at
34:19various time points over those 3 years.
34:21We looked at the microbes using shallow
34:23shotgun sequencing and we looked at the
34:25metabolites using NMR spectroscopy.
34:29When we look at the microbes, what we
34:31see is those with elevated likelihood
34:34have higher amounts of Clostridia. So,
34:37you can see that here in these red bars.
34:38Um they have higher amounts of
34:40Clostridia, but they also had
34:41significantly lower amounts of
34:43Bifidobacteria. And Bifidobacteria tend
34:45to be associated with more beneficial
34:47outcomes in early life. So, those with
34:50elevated likelihood and lower bifs and
34:52higher Clostridia.
34:55And what we also found when we looked at
34:57the fecal metabolites,
34:59we see a really interesting finding
35:01here. So, GABA, gamma-aminobutyric acid,
35:03which is a neurotransmitter. Now, bear
35:05in mind this is in the stools, was
35:07higher. So, it has this bloom in in
35:09early life, around 5 months of life,
35:11this is high in the stools of the low
35:13likelihood group, and then declines with
35:15time. And because this is GABA measured
35:17in the stools, we're fairly confident
35:19this is GABA produced by the microbiota.
35:22And we think this is interesting because
35:24GABA has this important impact on
35:27neurodevelopment. So, around 5 to 6
35:28months of life, it switches from being
35:30an excitatory neurotransmitter to being
35:33an inhibitory neurotransmitter. And it
35:35seems the microbiota produced high
35:36amounts in this time window and then
35:38declines with time.
35:40But when we look in the elevated
35:42likelihood group,
35:43you don't see that same peak in early
35:45life. The microbiota does not produce
35:47this. So, to try to explore what was
35:50driving this, we did some correlation
35:51network analysis.
35:53And what you see here, so the red edges
35:55here are positive correlations, the blue
35:57are negative. And what we see when we
35:59look at GABA, is we see a whole range of
36:01bacteria positively associated with this
36:03neurotransmitter. So, we hypothesize
36:05that they can synthesize this
36:07neurotransmitter. Whereas the Clostridia
36:09were negatively associated with that
36:11neurotransmitter, so we hypothesize that
36:13they could be consuming it.
36:15So, to test this hypothesis, we explored
36:17what um precursors the microbes could
36:20use to make GABA, and we grew them in
36:22different cultures.
36:25So, just for for brevity here, so you um
36:27this is what some cultures where we've
36:29had putrescine.
36:31And these bars indicate the amount of
36:33GABA in the media.
36:36So, this is just straight media, so this
36:38dashed line is how much there at the
36:40start. If it goes above the line, it
36:42indicates synthesis, it's being
36:43produced. Whereas if it goes below the
36:45line, it indicates consumption. And
36:47consistent with this, we saw that the
36:49bifidobacteria can produce GABA, whereas
36:52the clostridia could consume it. And
36:54just a really important point to make
36:56here is that
36:58um a lot of criticism comes for
37:00exploring the microbiome in autism
37:03spectrum disorders is that um
37:05individuals living with ASD tend to have
37:07quite different dietary preferences, and
37:09that can confound or obscure some of the
37:12differences. That's going to result in
37:13differences to the microbiota. But these
37:15differences we see here are all at 5
37:17months of life when all of the infants
37:20were being breastfed, so there's no
37:21dietary variation at this time point.
37:24So, we actually started thinking, is
37:26there something in the balance of these
37:27bifidobacteria over clostridia? So, we
37:29started doing some co-cultures.
37:31And here, this is a positive control
37:33where we just have uh just GABA starting
37:36in the media, but no bacteria. And then
37:39if we have two times more clostridia
37:41than bifidobacteria,
37:42then all of that GABA gets consumed.
37:45Whereas if we tip the balance more in
37:47favor of the bifidobacteria, you don't
37:49see that same level of consumption. So,
37:51what this suggests is we need to stop
37:53thinking about the bacteria in isolation
37:55and actually start thinking about them
37:56more as compositions and imbalances.
38:00Uh I'm going to skip through this fairly
38:02quickly, just so I'm running out of
38:03time, but just to say um we're now
38:05developing ways that we can explore
38:07this. So, here we were growing different
38:09probiotic candidates and measuring the
38:11metabolites they produce to try and find
38:13those that could produce neuroactive
38:14compounds. We've then fed this to flies,
38:18um these probiotics to flies, where we
38:20can then take the heads of the flies and
38:21look at how the metabolites change. And
38:23the reason why I raised this here is you
38:25can see in particular these two
38:26probiotic candidates we identified could
38:29increase the amount of GABA in the fly
38:31head. So, it's a nice tool for screening
38:34potential probiotics that can then be
38:36taken further into uh human feeding
38:38studies.
38:40So, that leads me lastly onto the
38:41diet-induced effects on the microbiome.
38:43Now, we know that the microbiome can be
38:45affected by a whole range of different
38:46factors, different pressures, with
38:48things like exercise, your genetics,
38:50geographic location, but really here I'm
38:52just going to focus on the diet.
38:55And we know with things like prebiotics,
38:57actually this is one of the attractions
38:58about the microbiota-gut-brain axis. Um
39:01so, the fact that the microbiota is
39:03accessible for manipulation and the fact
39:05that it's malleable for manipulation, we
39:07can actually get in there with things
39:09like dietary components and actually
39:11change it with um downstream effects
39:14then on things like the brain. And so,
39:16we showed here using this as a
39:17prebiotic, beta-galactooligosaccharide,
39:20to show giving from an early life we
39:22could change the establishment of the
39:23microbiome, which could impact on the
39:25neuronal signaling, which could impact
39:27on behaviors and metabolites.
39:31And then in terms of things like
39:32probiotics, there's quite a large range
39:34of studies done now on depression and
39:36anxiety. And you can see here there's a
39:38couple of meta-analyses. So, this is
39:40from 2024. This was 12 RCTs involving
39:44700 participants. Here they showed a
39:46significant reduction in depressive
39:47symptoms based on when the BDI scale was
39:50used, but there was no observations or
39:53lack of significant effects when other
39:54scales were used such as the MADRS. So,
39:56this would suggest there's a mixed
39:57results there across different scales.
40:00This was a larger one done last year. Uh
40:02here's 72 RCTs, over 3,000 intervention,
40:06nearly 3,000 in the control, and they
40:08demonstrated again significant
40:10reductions compared to placebo in
40:11depression uh where the probiotics were
40:14also shown to improve sleep quality.
40:17So, it does seem that there is
40:18increasing amount of studies done
40:20exploring this with some favorable
40:22outcomes somewhere um
40:24there was no effect seen.
40:26And in terms of cognition, again, this
40:28was a one from last year. Here 34 RCTs
40:31were done nearly 2,000 participants
40:34showing that probiotics could have an
40:35impact on cognitive function, but it
40:37seemed that there were again some quite
40:39variable quality in some of the ways the
40:41studies were done. And that was the same
40:43thing that was kind of identified in
40:44this this paper as well.
40:47So, in terms of future gaps or current
40:49gaps, future perspectives, one of the
40:51area what that's relatively under
40:53explored is the importance of the small
40:55intestinal microbiota. Now, we know that
40:57the colonic or large intestinal
40:59microbiota is much bigger in terms of
41:01numbers of who's there, but we think the
41:03small intestine is important cuz it's a
41:04major site of absorption.
41:07But, one of the reasons why it's
41:08understudied is quite hard to get in
41:10there and sample the small intestine.
41:12But, what we're seeing more and more is
41:13the development of these small capsules
41:15that you can take and they can actually
41:17sample the small intestine at variable
41:19variable times various times. And so,
41:21this suggests that going forwards in the
41:22future we might see more and more
41:24research into the small intestine.
41:27Another underexplored area is the
41:28mycobiome. So, this is the fungal
41:30portion of the mycobiome and
41:33we think this is going to be explored
41:35more and more in the future and the fact
41:37that lots of these these fungi can
41:39produce neuroactive compounds and
41:41including some psychedelics. And we're
41:43also exploring the use of potential
41:45psychedelics for for mental health and
41:48so exploring the way the psychedelics
41:49can also impact on the gut-brain axis.
41:52And then just lastly, fecal microbial
41:54transplants people are probably getting
41:55familiar with now, the idea that you can
41:57transfer feces from one individual into
41:59another and that helps to establish a
42:02nice stable intact microbiome. It's been
42:04shown to have very
42:06uh been very effective in things like C.
42:08difficile infections.
42:11And we're seeing this increasingly
42:12applied or explored to be leveraged for
42:14things like the gut-brain axis.
42:16Um so this was a studies was showing
42:18promising results for Parkinson's
42:20disease and we're aware that there are
42:22ongoing or preliminary studies now
42:24looking at things like depression,
42:25anxiety, Alzheimer's, multiple
42:27sclerosis, and COVID and brain fog as
42:29well.
42:31Um and so just a summary then take home
42:33messages. We know that the gut microbes
42:35can influence brain function. Hopefully
42:37I've demonstrated it can impact on
42:38things like appetite, emotional
42:40behavior, cognition, and that can occur
42:42through things like biochemical, immune,
42:44neuro signal signaling.
42:46Uh also that this axis is modifiable. We
42:48can reach it with pre-probiotics, fecal
42:51microbial transplants, the diet, which
42:53can shift that microbial ecology with
42:55downstream effects on brain relevant
42:57processes. And then lastly, the future
42:59looks bright. There's a whole range of
43:02different approaches being applied,
43:04whether that's the use of psychedelics,
43:05more exploration of the microbiome, um
43:08and then there's also work underway to
43:10for like targeted silencing of of more
43:13harmful microbial outputs. Uh and so
43:16yes, so this this is still in its
43:18infancy, this field, but it's expanding
43:19rapidly. So with that, I will
43:21acknowledge all the people that
43:22contributed to this work and I'm happy
43:24to take any questions. Thank you very
43:26much.
43:30>> Thank you so much, John. That was
43:32incredible. I feel like you just threw
43:33threw the kitchen sink at us
43:35>> [laughter]
43:35>> in terms of studies and research. So so
43:38thorough and yeah, lots of papers there
43:39that actually hadn't um came across
43:41before. So yeah, thank you so much for
43:43taking us through that. Um we're going
43:45to now, like you said, going to move
43:46into a time of Q&A. So please do feel
43:49free to add your questions in the chat
43:52function
43:53um or feel free to check out our
43:54resources on our website as well.
43:57I think this is a a common question
43:59whenever it comes to us talking about
44:01the gut microbiome is around
44:03personalization.
44:05So do you think these kind of like
44:07personalized microbiome therapies will
44:09outperform broad approaches such as
44:12probiotics or dietary interventions?
44:14Like what's your kind of thoughts on I
44:16guess that personalization whenever it
44:18comes to gut microbiome?
44:20>> Yeah, I think we're not there yet cuz
44:23it's the whole the classic we don't
44:24quite know what normal is.
44:26Um
44:27we we don't know everyone's got this
44:28unique individual microbiome. So, if you
44:31looked at
44:32um your microbiome, we wouldn't know
44:35what advice to give you. Where what do
44:36we actually want it to look like? Is it
44:38developed and tailored to your exact
44:40lifestyle?
44:41Um and so right now it it we don't know
44:44what that core microbiome should look
44:46like. I know there's big studies
44:47underway where, you know, hundreds and
44:50thousand hundred thousands of people are
44:51being studied to try and understand what
44:53that normality looks like, but we're not
44:55quite there yet. So, I think for now
44:58yeah, we're not quite there with the
44:59personalization.
45:01>> Watch this space. More research needed.
45:03The the famous phrase.
45:04>> Yeah, exactly.
45:05>> [laughter]
45:06>> Um lots of really nice comments coming
45:08in thanking you for the fantastic
45:10presentation, really insightful. Someone
45:12has asked that you noted the importance
45:14of fungi and what are your thoughts on
45:16spermidine, if I can pronounce that
45:17correctly, and is there a promising
45:19pathway in exploring this space,
45:21especially in cognition and aging?
45:24>> Ooh,
45:25you know what? I'm not familiar with the
45:26literature on spermidine. Um so, it's a
45:28polyamine that um I there was some
45:32research Yes, there was some research I
45:34did a little while ago showing promising
45:36effects, but I can't off top of my head
45:38recall what it was. I know there's some
45:39links between metabolic health and
45:41spermidine.
45:42Um but but I'm trying to remember what
45:44it was about spermidine.
45:46Yeah, I don't know. Sorry, off top of my
45:48head.
45:48>> No, no, you're grand. Thanks. Um someone
45:50again, really fascinating. Thank you so
45:51much. If you could make one manageable
45:53recommendation for the general public to
45:55improve their gut microbiome, I guess
45:57specifically in the context of the
45:58gut-brain axis, what would it be?
46:01>> Yeah, so I always put this is a bit of a
46:03cop-out, but I always say fiber because
46:05um
46:06>> Fiber is king.
46:07>> It's it it it genuinely is, and it's
46:09cheap.
46:10>> [laughter]
46:11>> Um
46:11and, you know, it it stimulates the
46:14growth of beneficial microbes, but also
46:16from a gut health perspective,
46:18um helps with uh like motility, transit
46:21time, which we know can also impact
46:24beneficially, uh can impact on yeah,
46:26that barrier permeability. So, has that
46:29wide-ranging effect. So, yeah, a bit of
46:31a cop-out, and
46:33uh for a more sexy one, maybe the whole
46:35eat the rainbow, uh get more polyphenols
46:38in your diet, which can again stimulate
46:40the growth of beneficial microbes, but
46:41then also
46:43uh get the production of things like um
46:46antioxidants as well, which can also
46:48assist.
46:49>> Yeah, I'm glad that you mentioned
46:50polyphenols cuz that's the that was one
46:51of our webinar topics with Professor Ana
46:55Rodriguez-Mateos from KCL. So, yeah, she
46:57took us on yeah, a deep dive with all
46:59things polyphenols. So, yeah, a bit of a
47:00shout-out for that. Watch that back on
47:02our website for anyone who missed that.
47:04And yeah, I totally agree, John. I think
47:06fiber is is totally king. I think yeah,
47:08it's people joke it's the new protein,
47:10but yeah, rightly so. It's boring, but
47:12yeah, it's it's what we all definitely
47:14need more of. I know you touched a bit
47:16on
47:18like gaps in research and future
47:19research.
47:21What sort of um is there any sort of
47:22like particular emergent technology
47:24that you think will have the greatest
47:25impact on the gut-brain axis field?
47:30>> That again, that is really interesting.
47:31And just if I I've I've still got
47:33control, can I go back a slide?
47:35>> Yeah, I think if you click, you should
47:36be able to go back.
47:37Like click on your um keyboard, yeah.
47:39>> technology. So, just a highlight to
47:41everyone, if you're not already a
47:41member, to to explore the UK
47:44gut-immune-brain axis network, so please
47:46sign up there. And the reason why I
47:47raised that is cuz the point of the
47:48network is to try and pull together
47:50people working in different disciplines.
47:52And one area I'm really interested in is
47:55things like wearable tech and getting
47:57engineers more involved. So, if we can
47:59uh
48:00whether it's measuring things like heart
48:01rate variability for vagal tone,
48:05just the ability to capture more data
48:08and data in real-time on the microbiome.
48:11I think that's the next step, the next
48:13knowledge gap to really advance our
48:15understanding in this area. We know
48:16we've got things like the circadian
48:18system,
48:19you know, what is the impact of things
48:21like shift work or jet lag on the
48:24gut-brain axis. Can we leverage that in
48:26our favor? I think that offers a real
48:29promise going forward. And we know that
48:30sleep's super important.
48:33We've got data showing that poor sleep
48:35precedes dips in mental health.
48:38There's some evidence of microbes
48:40improving sleep quality, sleep
48:43performance.
48:44And so all these things trying to trying
48:46to pair them together and finding ways
48:47to study them, I think that's the real
48:49area going forward.
48:50>> Yes, I think it's all about your fiber
48:52and your sleep. So, those are the two
48:53things that stand out for me personally.
48:55>> Yeah.
48:57>> Um I know obviously you mentioned about
48:58bile acids. Someone's asked, do you see
49:01differences in individuals who've had
49:02their gallbladder removed?
49:05>> Uh that's a good point.
49:07We haven't done that study, but I'd be
49:08amazed if well, won't be amazed if that
49:10research hasn't been done. I'd be amazed
49:12if there weren't differences in in
49:15those. Um
49:16I mean you see things like
49:19ursodeoxycholic acid being given a
49:21treatment for so I think that might even
49:23be people that have had their
49:25gallbladder removed might get
49:27ursodeoxycholic acid as a supplement,
49:30um which again can impact on various
49:32different pathways and signaling
49:34pathways, which can impact on energy
49:36metabolism as well as brain effects.
49:38>> Mhm. Thanks so much. Someone's asked
49:41quite a specific question, but their
49:43special interest is in brain health,
49:45specifically related to prevention and
49:47management of concussion in sport.
49:49They're wondering if you happen to have
49:50any advice related to gut in that
49:52contacts and that's quite niche in terms
49:53of yeah, brain health related to
49:55prevention management of concussion.
49:58>> No, again, I'm not familiar with any
50:00research in that area in terms of the
50:02gut brain axis.
50:03But would yeah, be very interested in
50:05exploring that actually. So if there
50:07were
50:08I presume samples
50:11where where that's quite an acute
50:13rapid um impact, you would imagine that
50:17sampling getting samples with that sort
50:19of analysis would be relatively simple.
50:21It's not like something like with the
50:22Alzheimer's where you have to collect
50:24years in advance prospectively. Um so I
50:26imagine concussion could be quite an
50:28interesting study to do.
50:30>> Maybe this links into another question,
50:32but I I think there's a lot of um maybe
50:34PhD researchers here thinking about
50:36longer term, you know, research plans
50:38and maybe postdocs and things like that.
50:40So if you're advising a young scientist
50:43who's maybe wanting to move into the gut
50:45brain research space, what sort of
50:48question do you think they should be
50:49focusing on answering or is there any
50:51sort of hot topic within the gut brain
50:54axis if someone was kind of looking
50:55specifically in the research kind of at
50:56the early stages of the career?
50:58>> Ooh, yeah, so I know one one area is
51:01getting and it's probably biasing me
51:03because of the current slide, but one
51:04area that's getting a lot of attention
51:06the minute is things like menopause and
51:07mental health and menopause. Um there's
51:09there's a lot of research getting
51:11underway in that and looking exploring
51:13the impact of things like
51:14potential pre and probiotics in that
51:16area.
51:17Um I think fecal microbiota transplants
51:20is a an area that's getting a lot of
51:22attention and um and and finding
51:25alternatives to that. So whether that's
51:27making synthetic communities, so rather
51:28than having uh a stool microbiome that
51:31can be quite variable and um
51:34difficult to uh sort of standardize,
51:37trying to find kind of 12 or or 20
51:42composition microbio microbial
51:44communities to use instead. That's a big
51:47area going forward as well.
51:49Other areas, yeah, I mean there's so
51:52many topics. I mean, yeah, the whole
51:54something we're actually doing right now
51:56as part of the GABA network is trying to
51:57explore the impact of these GLP-1
52:00agonists on the gut brain axis cuz
52:02they're given to to even children now
52:05these these
52:07I've forgotten the name of them.
52:08Manjuro? Manjuro and
52:11>> Ozempic?
52:11>> Ozempic, that's the one.
52:13So they're given to even to children. So
52:14what impact is that having on like the
52:16development of appetite centers and on
52:18the gut brain axis?
52:20So yeah, there's lots.
52:23>> Yeah, I think yeah, it's definitely an
52:25area to for any young scientist to get
52:27into.
52:28Yeah,
52:28you definitely you definitely wouldn't
52:29be stuck of research topics if we look
52:31at that.
52:31>> [laughter]
52:32>> I guess jumping on what you
52:34and you mentioned GLP-1s. So we've had
52:36two separate questions. One person was
52:38interested in knowing a little bit more
52:39about the association of the gut brain
52:41axis and obesity. And then someone else
52:44interested me was asking if you could
52:45share a bit more about the idea of
52:47eating disorders and some of the recent
52:48research around the gut brain axis.
52:52>> Yeah, in terms of obesity, I mean some
52:54of the very early initial work on the
52:56microbiome was done in obesity where
52:58there were quite clear differences in
53:00obese people versus lean people.
53:02Some of that initial Jeff Gordon work.
53:05And it there was a lot of work going on
53:08for a for a while there about 10 years
53:10ago on how short-chain fatty acids could
53:13be used to impact on appetite to try and
53:16combat obesity. But then I guess the
53:19GLP-1 agonists have come out and kind of
53:20taken a hammer to that.
53:22Then but
53:25What was the question? The appetite? The
53:27feeding
53:28>> One person was asking about obesity and
53:29then someone yeah about eating
53:30disorders.
53:31>> So
53:33some of that initial work did show that
53:35fecal microbiota transplants to mice did
53:37result in the mice developing obesity
53:39and that you could transfer that that I
53:42it's based on caloric calorie harvest.
53:45The ability uh a sort of obese
53:47microbiome is better at harvesting
53:48calories um from the food. And then in
53:51terms of eating behaviors uh eating
53:53disorders, there is there's quite a few
53:55studies now looking at the impact of
53:58anorexia on uh the gut microbiota to the
54:01gut-brain axis. Um still a bit of a
54:04watch this space at the minute, but
54:06quite often you also see increased
54:09exercise with um people with anorexia.
54:12And so trying to disentangle the
54:14extreme exercise with that lack of
54:18nutri- nutrition um it's yeah, it's a
54:21very interesting area. And I think we're
54:23still kind of relatively early in that.
54:25>> Mhm. Yeah, I think yeah, so true. Like
54:26you said, there's so many factors that
54:28impact the gut microbiome. So trying to
54:30yeah, disentangle that, identify, you
54:32know, where is that cause and effect and
54:34what's it coming from.
54:35>> Yeah. Yeah. Um
54:37I think there's some work as well in
54:39bulimia.
54:40Um
54:41yeah, so there's lots of studies ongoing
54:43and I think we're still in the early
54:44part of those.
54:45>> Yeah. Yeah, and they're really exciting.
54:47John, I think in the interest of time,
54:48we will leave it there for the
54:49questions, but I see yeah, lots more
54:51coming through. Um but yeah, I'm sure
54:53John, you're happy to uh keep the
54:54conversation going offline if anyone has
54:56any specific uh queries or things that
54:58they'd like to chat to you a bit more
55:00about. But yeah, lots of very, very
55:01complimentary messages saying how much
55:02they enjoyed it. Really fascinating. Um
55:05so yeah, thanks so so much again, John.
55:07Um as I mentioned earlier, this is our
55:09fifth and final webinar. So yeah, we've
55:11been going out with a bang on a very hot
55:13topic of the gut-brain axis. But our
55:15entire webinar series is now available
55:18on our website. So we've covered topics
55:20such as fiber, polyphenols, like like I
55:23mentioned, I know John mentioned the
55:25female gut microbiome is really um a hot
55:27topic at the moment. So we had a session
55:30focusing on endometriosis. Um we had
55:33another session on IBD. And then today's
55:35session on the gut-brain axis will be
55:37going live on our website too if you
55:39want to watch back and geek out again.
55:41So yeah, please do share it with anyone
55:43else as well that might be interested in
55:45any of those particular topics. And then
55:47lastly, just a massive thank you again
55:49to John for sharing his time and his
55:51expertise with him with us all sorry and
55:53also thank you all for attending. I
55:55appreciate it is incredibly warm today.
55:57So yeah, thank you for giving up not
55:59only part of your lunch break but also
56:01part of your lunch break on an
56:02incredibly hot day whenever you could be
56:03outside in the fresh air. We really
56:05appreciate it. But lastly and very very
56:08importantly, I do want to give a shout
56:10out to Tiffan and Lucy who are my
56:13absolute dream team. So whilst you've
56:15seen my face on the screen this
56:17lunchtime, it absolutely is not a one
56:19woman show. Tiffan and Lucy have done so
56:21much incredible work in the background
56:23for this entire webinar series helping
56:25with promotion, getting the word out
56:27there, all the graphics, reaching out to
56:29speakers, checking slides and yeah,
56:31they're absolutely amazing. So it's only
56:33right and just that I give them a
56:34massive shout out to both of them. And I
56:36kind of one bad thing about being on a
56:38webinar is that we can't really give a
56:39round of applause otherwise I'd be
56:41giving a massive round of applause to
56:42John and also Lucy and Tiffan. And then
56:45lastly, I'll just say
56:46if you would like to we'd really
56:47appreciate if you could give us some
56:48feedback whether this your first webinar
56:50you've joined or whether you've joined
56:52quite a few in the past. We always we
56:54read every single answer and take it on
56:55board. So yeah, always happy to receive
56:58any feedback or any thoughts on future
57:01topics that you'd like to hear about or
57:02future speakers. But again, big thank
57:05you all for joining, a big thank you to
57:06John for his expertise and thank you
57:08again to Lucy and Tiffan and hopefully
57:11you'll be able to join a future webinar
57:12or a future in person event very very
57:14soon. But thank you so much and enjoy
57:16the rest of your day everyone.

About this transcript

This page contains the full transcript of The Gut–Brain Axis: Hype or Clinical Reality? by Yakult UK & Ireland, generated from the public captions YouTube serves with the video. The transcript has 10,387 words across 1,684 segments, with the original timestamps preserved so you can click any line to jump to that moment in the embedded player.

What you can do with it

Use the transcript to take notes, quote the speaker, build a study guide, generate a summary with ChatGPT or Claude via the YouTube Summary tool, or export it as a timed subtitle file with YouTube to SRT. You can also re-open it in the transcriber to translate the transcript into 100+ languages.

Free YouTube transcript tool

YouTube2Text is a free YouTube transcript generator — no signup, no daily limit. Paste any YouTube link and get the full transcript instantly, with timestamps, click-to-jump, translation to 100+ languages, AI prompts for ChatGPT, Claude, and Gemini, and exports to TXT, SRT, VTT, or Markdown.