Gut bacteria and mind control: to fix your brain, fix your gut!
Brain-friendly gut bacteria grow well when you eat essential foods.
Gut Bacteria Are Important for your Health
I’m going to try and inform you a little bit about what goes on in your gut. In particular, all the microbes that live in your gut. I will tell you why microbes are so important for your health. Under some conditions, microbes can actually cause quite a severe disease.
So there’s been a significant shift in our understanding of what causes disease.
We’ve always thought of disease has to do with who we are, our genes, and then the things we do as we go through life. Now we know that lifestyle keeps us healthy or causes disease. Lifestyle is what we eat and what we get exposed to in the environment.
But what’s apparent now is that in the middle of this and that may be involved in interpreting a lot of these things that we do and eat, is that our gut microbes have a direct link to our genetic material and they can in turn influence how we react and respond to things in the environment and how
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they can keep us healthy or or not and
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really the understanding of gut microbes
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has really taken a fantastic leap since
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around 2000 this graph here shows the
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number of scientific articles that have
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been published about gut microbes and
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you see they really started to take off
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here around 2002 and that’s because of
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Technology so before 2002 the only way
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we could really identify and
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characterize I’ve got microbes was by
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what we could culture on a petri dish
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and since we now know that about 80
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percent of our gut microbes can’t be
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cultured that really isn’t a good
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representation of what’s in our gut but
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then with the advent of gene sequencing
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technology we can now identify microbes
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according to their genetic blueprint and
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what’s apparent is that different types
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of bacteria have a unique genetic
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fingerprint so if we can identify the
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fingerprint we can say whether or not
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they’re present or absent and this as I
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said has led to this huge explosion in
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this area of research we can now
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identify microbes we can
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culture and so this has led to massive
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interest in gut microbes and some of
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these are very recent so the Daily Mail
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thinks that healthy gut bacteria might
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be linked to anxiety and then we’ve got
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others that linking gut brain connection
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autism probiotics as a means of treating
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diseases and then a couple of books this
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one has just come out and those of you
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in the Institute will notice the
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significance of broccoli on the front as
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the Institute is responsible for
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generating strains of broccoli that have
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lots of nutrients good beneficial
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nutrients in them but really the message
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here is that what we eat influences our
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microbes which in turn can influence our
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brain function and keeping it normal but
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as always we have to be aware of the
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hype okay so whenever we read these
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articles we need to have a couple of
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things in mind that allow us to
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determine whether or not you know
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there’s some factual basis to it or
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whether it’s hype and these are some of
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the questions that I would say you need
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to ask so the obvious one is well so
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what do these differences they’re
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detected do they really matter are the
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changes a cause or a consequence of the
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disease and of course we want to know
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how it works what’s the mechanism so is
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there anything in this article that
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allows us to understand how it actually
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works and then a lot of experiments are
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carried out on animals because we can’t
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do many interventions in humans for
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ethical reasons
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so another aeneas question is well is a
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mouse a small human no it isn’t so we’ve
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got to bear that in mind and then
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obviously we’ve got to think all is
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there something else they haven’t looked
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at which could explain what they’re
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describing so behavior in lifestyle
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are two important things so I’m going to
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try and sort of touch on some of these
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things in the rest of my talk so this is
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what I’m going to cover I think I need
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to introduce the gut to you I’ll talk a
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little bit about microbes some
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interesting facts a little bit of trivia
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and then how gut microbes may play a
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role in determining what we eat and what
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the consequences of what we are for our
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health
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well being and then how we actually
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might manipulate they’ve got microbes to
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improve or restore our health so that’s
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what I call lawn care right start with
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so did the guts mouth to the anus it’s a
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long tube here’s a picture taken with an
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endoscope and you can see it’s not as
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smooth tube it’s got these ridges to it
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the muscles this is what allows food to
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be propelled through the guts but it’s
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not a smooth chew it has lots of finger
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like projections that we call villi that
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stick into the lumen to capture
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nutrients and absorb them so the tube is
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quite long it’s like nine meters from
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mouth to anus and somebody has taken the
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trouble trying to calculate what the
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surface area of all these villi are and
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the outcome of that is it’s probably
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about the size of a badminton court so
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it’s an incredibly large area and it has
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to be large in order to take up the
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nutrients that are in your diet to keep
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you healthy and then we also consider
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the process of digestion and the gut is
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in fact a massive bioreactor so we take
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in foods plant material for examples and
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they’ve broken down first of all in the
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small intestine here where the small
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simple sugars are absorbed and then the
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larger more complex plant material that
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we eat in our diet passes through into
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the large bowel or the colon where it’s
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fermented and it’s fermented by the
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bacteria that live in the colon and the
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end product of all of this is something
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called short chain fatty acids which are
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very important because they can provide
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about 5 to 15 percent of our daily
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energy requirements in some animals it’s
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up to 30% so this has to be a very
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efficient process to keep us alive
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basically and the enzymes that are
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responsible the proteins that digest
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these food material and the
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polysaccharides now we only have about
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20 genes in our whole genome that will
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allow that encode proteins
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we’ll break down these carbohydrates but
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one bacterial species this one in
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particular Bacteroides has 260 and you
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think there are thousand species so
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that’s a vast number of proteins that
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can digest the digest our food so the
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bacteria that live in our colon are
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ideally suited for processing our food
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and extracting the maximum level of
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nutrients from them so it’s a bioreactor
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a little bit about the microbes so the
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gut is packed full of microbes there is
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no space that endoscope image I showed
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you they’ve displaced and rinsed out all
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the bacteria normally that will be
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jam-packed with bacteria most of them
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are floating free in lumen but a large
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number of them actually make physical
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contact with the cells that line our gut
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so there’s actually some intimate
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Association of these microbes with our
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gut and there are two terms that we you
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may come across we use to describe these
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microbes the microbiota which is to
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describe all the microorganisms that
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live in the gut and there’s the
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microbiome and that’s all the microbes
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plus all their genes combined so
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microbiota microbiome – as you may have
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come across in a lot of these articles
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but individually bacteria incredibly
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small so this is a head of a pen under
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an electron microscope and each of these
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orange dots represents one bacterial
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cell so you can see that you can get
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lots of bacteria on the top on the tip
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of a pin they’re incredibly small but
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well though they’re small they make up
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for that in their vast numbers so we
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have about 10 trillion cells in our body
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but we actually have ten times that
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number of bacteria in our body and so on
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this scale here we have enough cells it
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would fill half of one of our legs all
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the rest of the body will be filled up
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with microbes bacteria and then if we
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think about all the DNA that we have oh
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this is an interesting quote sorry I
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forgot about this this ninja just give
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you an idea of the scope and scale of
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the numbers here of bugs a bacteria in
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our colon so just one linear centimetre
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contains more bacteria than all the
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humans that have ever been born it’s a
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vast number of microbes and then the DNA
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elements this is the big toe okay and
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that represents the DNA in our body that
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is actually ours okay so everything else
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more than 99% of the DNA is bacterial
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DNA so you know just think about that
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that’s actually quite amazing really so
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we are carrying around a lot of DNA but
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very little of it is our own okay now
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this is the audience participation bit
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some trivia how much do you think all
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the microbes in our body way don’t be
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shy PhD students at the back come on how
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much what
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that’s not conferring su nope
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anybody else kilogram closer to
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kilograms two to three kilograms a lot
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right a couple of bags sugar and if you
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put it in a volume size about one and a
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half liters and there’s about a thousand
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different species thousand different
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types packed in there and this is what
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they need to keep them healthy about 50
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to 65 grams of these things which are
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sugars to keep them healthy so that
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amount is needed every day just to keep
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your microbes healthy and then you’ve
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got all the other things that you need
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to keep your body healthy and so a
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product of all this metabolism is gas
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so how much do you think we expel every
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day and this is everybody so it’s not
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just old men and teenagers everybody in
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this room expelled gas how much do you
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think we expel every day how many liters
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how many five that’s a bit high anybody
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else
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one two four that’s a lot and of course
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at the end of all this we have waste so
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60% of your stool is made up of bacteria
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live and dead okay so that’s trivia
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interesting thing just before you have
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your meal you can run through some of
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these facts and figures but they are
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very very important and we know they’re
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very important because of animals that
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we can keep germ-free so these are
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animals that have never been exposed to
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any microbes they’re sterile and when we
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examine these animals they’re clearly
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compromised they’re deficient so they
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have nutritional deficiencies they don’t
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grow but interesting they live longer so
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if you want to live longer don’t eat
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that’s the bottom line they have a
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defective gut so their gut is not poor
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properly formed so it’s leaky and their
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immune system is very poorly developed
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so they’re very susceptible to
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infections and in fact if you introduce
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a pathogen to these animals it can kill
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them very quickly because they have no
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protection no immunity and also their
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development is affected as well so
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clearly we’re already starting now to
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move into the gut brain so that there
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are really poor animals very sick so the
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microbiota and the Mike Michaels are
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very important so your microbiota is
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unique to you it’s your identity it’s
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like your fingerprint your microbes are
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unique to you however the microbes you
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have are shared with other family
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members so there’s some commonality
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there and interestingly looking at
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the microbiota of monozygotic and
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dizygotic that side entacle non
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identical twins you know there’s no
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difference so even if you’re an
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identical twin you’ll have similar
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differences in your microbiota to non
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identical twins so what does that mean
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well it means that genes are important
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who you are is important but also the
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nurture the nature the nurturing is also
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important in shaping the microbes but we
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now know that we all have a core
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microbiota so there’s about 57 species
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of bacteria that we all share and there
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are two types that predominate in all of
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us here and not unsurprisingly
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these are concerned because they perform
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important functions such as ones here
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degradation of carbohydrates are
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degrading our plant material we eat they
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also provide these fatty acids that we
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need to keep us alive every day and also
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amino acids and vitamins which we can’t
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produce but our gut bacteria can so it’s
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not surprising there’s a core that all
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of us need to keep us healthy but then
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everything else all the other 800 of
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2,000 species are all unique to us so
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where do they come from well your
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parents in particular your mother so if
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you think you have bad bacteria you can
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blame your parents fully justified okay
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now originally it was thought that we
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were born sterile but that’s changing
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slightly is now evidence that we can in
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fact babies do get exposed in the womb
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to bacteria that the mother has and that
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can be through the placenta and also by
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other routes but by far the biggest
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source or time point at which you get
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exposed to microbes is soon after birth
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because if you believe we are born still
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then the bacteria can colonize very very
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quickly so the first few months after
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birth you’re rapidly being colonized by
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bacteria the types of bacteria depend on
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the delivery so if it’s vaginal delivery
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then most of the microbes that will
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colonize the baby will come from the
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mother
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if it’s a c-section then the bacteria
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actually come from the people in the
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operating theater handling the baby and
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most of those will be skin type bacteria
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and that’s important because there are
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now evidence that links later onset of
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various diseases and disorders back to
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whether or not you are vaginally born or
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from a c-section and the types of
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microbes that initially colonize the
15:46
body other things that will impact on
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the types of microbes that will colonize
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this infant are delivery so it’s a
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normal birth or is it just require
15:57
intensive care the age at birth is also
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important is it a full-term birth or
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preterm birth and hygiene obviously
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where you’re born the home versus the
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hospital at very different population of
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microbes that can colonize the infant
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and then after that things that will
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impact and cause alterations in the
16:17
microbes are antibiotics and again it
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depends on how many what types and for
16:23
how long and also very important is
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nutrition whether or not the infant’s
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breast or bottle fed and again the
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breast milk contains lots of ingredients
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including microbes which can colonize
16:36
that baby and keep them healthy but as
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we go older we get exposed to micro some
16:44
other sources and by different routes so
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via the nose and lungs we breathe
16:48
microbes in the mouth and the gut
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obviously the things we eat and through
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the skin and these are the sources so
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water and the food we eat will contain
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microbes we have pets if we live in a
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farm we’re getting exposed to microbes
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from the animals that we live with where
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we live do we live in the country or do
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we live in the city the population of
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microbes again are very different and
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then the type of accommodation or the
17:17
dwelling that you live in you know is it
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single dwelling is it multi-dwelling all
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these people are contributing microbes
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that will you’ll be exposed to and then
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are you indoors or outdoors are you
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active are you inactive are you an Xbox
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fan
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or are you out playing football these
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things will all expose different types
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of microbes all of these are important
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because beyond three years of age your
17:44
microbiota is pretty much set for life
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so the early years of life are critical
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for the development of a healthy
17:51
microbiota however there are cultural
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things and social things that will also
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impact on the types of microbes that
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that populate us now here’s a fact most
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you probably didn’t know okay
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interesting one to experiment on
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so intimacy and you know it’s across the
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animal kingdom different types of
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interests me transfer of microbes
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grooming it’s another one nurturing food
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sharing right we often sit down at the
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table and eat together and we can be
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sharing food it’s a good way of
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transferring microbes and then there’s
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something that’s slightly less you know
18:45
Pleasant but animals do transfer
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microbes to their offspring via this
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route by regurgitation of food and
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transfer food as well as microbes so the
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message here is if you have some good
18:57
bacteria you need to share it because
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there are some of us poor less fortunate
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people scientists for one right I mean
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my wife is very fond of telling me I
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have very little culture so maybe my
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culture is my bacteria so share your
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good bacteria if you have them right so
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we have our microbiota we’ve been
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exposed we’ve got a stable population
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but it’s not the end of the story they
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do change and here we’ve got a
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representation of aging so here you can
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see these circles the different colors
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represent different types of microbes as
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we age you can see the colours change as
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the populations change and there are
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some differences between formula-fed and
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breastfed babies transition to solid
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food is a big one in terms of shifts in
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microbial populations
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and then you can see as we age there is
19:52
an also shift as well in the population
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ageing has an impact in itself but one
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of the most striking impacts is through
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antibiotic treatment and this slide just
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illustrates the impact of antibiotic to
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antibiotics to treat Clostridium
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difficile which is a severe infection
20:11
that is often acquired in hospital so as
20:15
a result of the outgrowth of this
20:17
bacteria we get sick
20:19
so we administered vancomycin or
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metronidazole and what you can see is
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the diversity the number of bacteria we
20:27
have in our gut is drastically reduced
20:28
because the antibiotics have killed them
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all but it’s also killed off Clostridium
20:33
difficile which is a good thing but you
20:35
know there’s a consequence of this in
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that we’ve wiped out a lot of our good
20:38
bacteria so too many antibiotics for too
20:42
long have a very profound and can be a
20:45
long-lived effect on our microbiota so
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antibiotics could be described as a
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man-made catastrophe however most of the
20:54
antibiotics that are used are used in
20:57
agriculture and in farm animals in
21:00
particular to check infection and solar
21:02
8 growth about 19,000 tons of
21:05
antibiotics are used in agriculture
21:07
every year and of course Antipodes get
21:10
excreted by animals and humans as well
21:12
so they can contaminate streams and
21:15
rivers and then get back into the food
21:16
chain and also giving antibiotics or
21:20
children has its consequences as well so
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in the u.s. by 2 years of age most
21:27
children had at least three courses of
21:29
antibiotics I mean a phenomenal number
21:32
of doses of antibiotics given out in the
21:33
US and what this does is it drives
21:36
bacteria to become resistant and this is
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serious okay so this particular organism
21:43
here mmrsa
21:45
now is resistant to most the antibiotics
21:48
that we have in the pharmacy and more
21:51
than 19,000 people here in the US are
21:54
killed which is much higher than number
21:55
of people dying from AIDS I don’t know
21:57
if you just seen on the news today but
21:59
there’s a UK government
22:01
review group is recommended the
22:03
pharmaceutical and it’s invest two
22:04
billion dollars in developing new
22:06
antibiotics there’s a real need for this
22:09
but one of the causes that we administer
22:11
too many antibiotics we take too many
22:13
antibiotics it leads to resistance
22:17
cautionary tale the other side of the
22:19
story is that gut microbes can actually
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work on drugs rather than been affected
22:23
by drugs they can also work on drugs the
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thing to bear in mind is that the vast
22:28
majority of drugs we take are given
22:29
orally and so the microbes in the gut
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can actually alter the drugs they can
22:36
alter their structure they can produce
22:38
factors that interfere with the drugs
22:40
and they can alter how the body reacts
22:43
to the drugs and here are some examples
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so the bad ones are these drugs here
22:49
which are painkillers anti-cancer drugs
22:52
drugs used to control high blood
22:54
pressure in certain individuals that
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have certain populations of microbes
22:59
administering of these drugs will lead
23:01
to increased toxicity and we some
23:04
antibiotic as well as a similar story
23:06
well there’s a good side to this as well
23:08
in that got microbes can process drugs
23:11
to make them more active more
23:12
efficacious such as this antibiotic here
23:16
and this anti-inflammatory drug so what
23:19
this means is that how you react to a
23:21
drug can depend on the type of microbes
23:24
you have in your gut and one of the
23:26
things that medicine is heading towards
23:27
perhaps is being able to administer or
23:30
prescribe you a drug based on the
23:32
population of microbes in your gut
23:33
because there’s no point in giving you a
23:35
drug that your microbes will make toxic
23:38
you want microbes to actually help the
23:41
drugs become better for you more
23:43
efficacious so this is what’s been
23:46
called personalized medicine the drugs
23:48
will be given to you because you have
23:50
been determined to respond best to those
23:53
drugs so then that brings me to really
23:57
the the meat of my talk here in a way
23:59
and this is what I’m going to try and
24:02
persuade you of that your gut microbes
24:05
can now influence what you eat when you
24:07
eat and what happens when you do eat and
24:09
so I formulated this hypothesis
24:14
that gut microbes influence their hosts
24:17
food choices and I sort of put up three
24:19
predictions in order to prove the
24:22
hypothesis could be correct the first
24:24
one is that the microbes you have in
24:26
your gut is a consequence of the food
24:30
that you eat and how you behave in the
24:32
environment so this interesting so it’s
24:36
not a map of the galaxies it’s actually
24:39
the results of screening them the micro
24:42
biomes in a lots of different animals
24:43
and this is sort of a zoo collection
24:45
each dot represents similar microbiota
24:50
in populations of animals and the lines
24:53
of separation here indicate how similar
24:55
or related they are to other micro
24:59
biomes and other animals so we’ve got
25:01
these sequences we know all the microbes
25:04
and this is how they all cluster so you
25:06
can see different clusters so horses and
25:10
rhinos are up here in their own little
25:12
cluster ruminants such as sheep and cows
25:20
make their own cluster elephants are
25:25
their own little grouping up here and
25:29
then we have the carnivores for the
25:31
lions and bears again they’re a
25:32
different cluster in red and then we
25:35
have leaf eating monkey serve vegetarian
25:37
monkeys and pigs and then the other
25:41
primates humans include we’re here so
25:44
we’re separate from the leaf eating
25:46
monkeys so what does this mean well it
25:50
means that who we are and what we eat
25:52
determines heavily influences the
25:56
microbes that populate our gut and
25:57
that’s reinforced by this study in
26:00
looking at the microbes that are present
26:03
in the gut of people that live in
26:06
Burkina Faso in Africa that have a rural
26:09
diet primarily vegetarian based diet and
26:11
Europeans and this is actually Italians
26:13
have a Western diet you can see just
26:15
looking at the colours they’re very
26:17
different ok and what’s interesting is
26:21
if that people in Africa migrated to
26:24
Europe to Italy and then adopt the
26:27
Western
26:28
they lose this and become this
26:32
distribution of microbes so they haven’t
26:35
changed terms their genes or anything
26:36
all they’ve done is that diets changed
26:38
and it’s causes profound shift in the
26:41
microbes so the diet really is a driving
26:44
force in making up the microbes that you
26:47
have in your gut there’s another example
26:49
this is a Burmese python so they go
26:52
through periods of fasting and then
26:53
feasting just looking at three different
26:56
types of bacteria in the fasting state
26:58
you can see very low levels but if
27:01
they’re given a meal you know within
27:03
half an hour you can see these striking
27:05
chips and expansions and increases in
27:10
certain types of bacteria and these will
27:12
eventually stabilize and then hours of
27:14
the animal goes back into a fasting
27:15
state they will decline again so fasting
27:19
reduces the overall diversity and then
27:22
feasting expands the diversity in
27:25
response to diet it’s a quite striking
27:27
so–that’s diet stress is another thing
27:32
we have to cope with in our environment
27:34
and this is some evidence that links
27:37
stress impacting on our gut microbes so
27:42
noradrenaline norepinephrine and effort
27:44
in which all polyp adrenaline are
27:47
produced in response to stress and that
27:49
can have a direct effect on the bacteria
27:52
that live in our gut and it can cause
27:55
the outgrowth the particular types of
27:56
bacteria so here for example ten
27:59
thousandfold increasing growth in
28:01
response to Adrenaline’s produce under
28:03
stress and surgery is a stress and this
28:08
bacteria here rapidly expands following
28:11
surgery and if it’s not contained then
28:14
it can cause sepsis and mice that get
28:18
exposed to a type of stress rapidly
28:20
change their microbial populations and
28:22
that’s just shown here so these are
28:24
normal animals in most the bacteria
28:26
little circular shapes but then under
28:29
food deprivation which is a form of
28:31
stress you know they rapidly changed the
28:33
rod-shaped bacteria and that was
28:35
observed over 40 years ago so we’ve
28:39
known for a while that stress is a major
28:40
factor
28:41
and then what’s interesting is that
28:45
probiotic bacteria that are present in
28:47
some of these health foods is well for
28:52
Morrison’s and this is Actimel they
28:54
contain bacteria that produce a
28:56
neurotransmitter called gaba and gammas
28:59
normally producing the body what it does
29:01
is it dampens down excitable neurons so
29:05
it relaxes you so and this is being used
29:10
by the pharmaceutical industry to
29:12
develop mimics of gamma so they can
29:14
overstimulate these receptors to make
29:16
you even more relaxed and in fact even
29:19
knock you out
29:21
because anesthetics can work by
29:23
mimicking the gaba that is produced by
29:26
these bacteria so benzodiazepines
29:29
alcohol right we all feel nice and
29:31
relaxed after a glass of wine or a
29:34
bottle of beer well you know one of the
29:36
ways that comes out about is that
29:38
they’re stimulating these receptors that
29:41
gut bacteria can do as well so the gut
29:43
bacteria can already you know hopefully
29:46
take us from a stressful state to a
29:49
relaxed straight state and so one of the
29:54
other things i wanted to highlight here
29:55
was this obesity lots of evidence in the
29:58
literature now and in the newspapers
30:00
that changed in our gut microbes to make
30:03
come acres of obese so gut microbes and
30:07
obesity so very this is a very
30:11
interesting experiment probably the best
30:12
experiment that demonstrates how
30:16
microbes can influence whether or not we
30:19
are be so lean so here we have identical
30:22
twins but one of the twins is obese and
30:25
one is lean so we’ve taken the stool
30:28
sample from each of these extracted the
30:30
bacteria what we’ve done is we put them
30:33
into mice the mice are then put on a
30:36
regular diet low-fat high-carbohydrate I
30:41
mean low-fat high-fiber diet the ones
30:44
that got the mic micros and the obese
30:46
twin become obese but the mice that got
30:50
the microbes from the lean twin stay
30:52
lean so that’s a direct call
30:55
all link okay so that’s not really
30:56
height that’s a bit more close to fact
30:59
so of course it’s my slits not humans
31:01
but this is the best evidence we have to
31:03
date that shows the direct causal link
31:05
between our gut microbes influencing
31:08
whether or not we stay lean or whether
31:10
become obese and then this was in the
31:12
Sunday Times this week this was from a
31:16
study carried out by Tim spectra at
31:18
King’s College London and he fed his son
31:21
I don’t know if his son was a willing
31:23
volunteer a high fat diet for 10 days
31:26
Big Macs and lots of coke and then he
31:31
was taking stool samples before an art
31:32
of it the 10-day diet and what happened
31:35
what he showed was that first of all is
31:37
a reduction in nutrients because he’s
31:39
now eating this very processed refined
31:42
foods there was a loss in number he’s
31:45
got microbes but he gained two kilos in
31:48
weight in just 10 days so the
31:51
interpretation of this is that highly
31:53
processed foods present in Big Macs
31:56
containing grease are toxic to certain
31:59
microbes and this leads to a loss of
32:03
diversity we’re losing microbes because
32:06
of this and if you want to know more
32:08
this individual has produced his book I
32:12
had nothing to do with it so I’m not
32:14
doing buy it or anything but if you want
32:16
to know more these books here so loss of
32:19
diversity is a recurring theme and in
32:22
fact I’ve already said in aging we have
32:25
this loss of diversity we lose richness
32:28
we lose microbes the same in obesity and
32:31
it’s the same in other disease in flicks
32:33
inflammatory bowel disease and Crohn’s
32:35
disease so the loss of diversity and
32:38
types of Micra 7 I got is not good it
32:42
can have quite profound health effects
32:44
and so it’s not just got diseases all of
32:48
these diseases shown here are linked by
32:51
a common theme in a change or shift in
32:55
the population of microbes in the gut
32:57
and generally that shift means less
33:00
diversity interestingly quite a few are
33:03
linked with diseases of central nervous
33:06
system nearly
33:07
generative diseases the heart the liver
33:11
fat and rheumatoid arthritis there’s
33:14
lots and this is a lot of complete list
33:16
by any means so obviously well is there
33:19
one microbe or one population of
33:21
microbes that can cause these diseases
33:23
so it’s like looking for Waldo found him
33:30
yeah there is the only problem is there
33:38
are lots of Waldo’s and so it’s probably
33:40
not one microbe it’s the combination of
33:43
microbes that when they get together you
33:45
know it’s a bit like a gang of teenagers
33:47
you know they could be rowdy or it can
33:48
be miserable and anti-social so it’s the
33:53
population when they come together that
33:55
they causes or is probably responsible
33:58
for the effects on our health it’s not
34:00
one it’s probably lots okay so moving on
34:04
to the predictions we’re now at the
34:05
second one so gut bacteria can by
34:09
influencing how our body works influence
34:11
our appetite and food preferences so I’m
34:15
sure this is a familiar scenario for
34:17
many of you you know our mind says no
34:19
take the healthy option but there’s
34:21
something inside of us and I really like
34:23
that piece of cake okay and it may be
34:25
that gut feeling you know I really am
34:28
hungry for a piece of pie rather than an
34:31
apple so what is the evidence that
34:35
normal gut microbes can influence brain
34:37
development and behaviors that’s what
34:39
we’re talking about brain development
34:40
behavior so this is next this is a
34:42
summary of an experiment carried out a
34:44
few years ago looking at our germ-free
34:46
mice again these are sterile Mice and
34:48
mice that have populations got microbes
34:51
this here shows the expression of an
34:54
anxiety related gene so the yellow
34:57
identifies high levels in the brains of
35:01
these mice that have got microbes but
35:04
very little expression in germ-free mice
35:06
and this maze here is a measurement of
35:09
how curious adventurous mice are so if
35:13
they’re cautious timid they’ll spend
35:16
most of their time in the enclosed
35:18
section away from the light but if
35:20
they’re adventurous like
35:21
this one you know they’ll be on the open
35:23
arms so what this study showed was that
35:26
gut microbes can affect normal brain
35:29
development and make these mice more
35:33
curious I’m sorry wrong way and perhaps
35:41
more creative and trying to escape
35:44
so it’s this fear extinction you have
35:48
got microbes you become a little bit
35:49
more cautious reticent a little bit more
35:52
anxious if you don’t have got microbes
35:54
you know it’s the Great Escape you’re
35:56
looking for ways out more striking
36:00
experiments this one shown here so we’ve
36:02
got two strains of mice what we’ll call
36:04
timid and adventurous so they’ve got
36:08
microbes of anything to do with why
36:09
these animals are timid or adventurous
36:11
and what we did so not well we did this
36:13
group in Canada did was they took the
36:15
stool from the timid Mouse isolated the
36:18
microbes and put it into an adventurous
36:21
Mouse and that Mouse became timid the
36:25
other way around they took the microbes
36:27
from an adventurous Mouse put it into a
36:31
timid Mouse and these are germ-free mice
36:34
so they’re they’re an empty vessel that
36:35
you can put the microbes into and they
36:37
became now adventurous so this is a
36:40
direct causal link again showing the gut
36:43
microbes can influence the behavior of
36:46
mice at least now is this translatable
36:50
to humans I can see probably some people
36:52
in you always thinking maybe I could
36:54
give this to my husband yeah would he
36:55
still be a grumpy old man if I gave him
36:58
some microbes and would you know if my
37:00
teenage boy had some microbes form you
37:03
know somebody maybe they become bit more
37:05
outgoing bit more social maybe no maybe
37:08
a few years from now maybe I’ll have
37:10
that but not just yet but I mean we
37:14
really shouldn’t be too surprised by
37:15
this because we now know that the gut
37:18
actually contains an awful lot of the
37:20
neurons neural circuitry that’s present
37:22
in the brain and it’s often thought to
37:24
be the second brain I mean it has a very
37:27
large number of neurons 500 million and
37:30
it produces lots of neurotransmitters
37:32
and you know there’s some
37:35
some evidence that sort of links that
37:37
got to the brain so brain-dead people
37:42
their stomach functions normally for
37:43
quite a while it’s almost an inherent
37:45
activity anybody that’s taken paint
37:48
major pain-killing drugs like morphine
37:50
for example you know the risk of
37:52
constipation it shuts down motility in
37:55
your gut and emotions and feeling are
37:58
intimately associate with bowel function
38:00
right we’ve all had their butterflies in
38:02
the stomach that nervous got action well
38:05
that’s all those neurons in your gut
38:07
that are firing away and when you look
38:09
at the structure of the nerves in the
38:11
gut that make up the enteric nervous
38:13
system you know these are the neurons or
38:18
the dendrites here in silver the white
38:20
color this is our gut tissue and you can
38:23
see that when we superimpose these two
38:25
the nerve fibers actually penetrate and
38:28
intermix between all our gut tissue and
38:30
they actually look like they’re actually
38:33
protruding into the lumen to be able to
38:35
sense perhaps the presence of factors
38:38
that they can respond to that are in the
38:40
gut looming that could be made by gut
38:42
microbes and the vagus nerve is
38:46
ultimately this the route by which all
38:49
this signaling in the gut leads into the
38:51
brain so all these signals here that the
38:54
enteric nervous system responds to are
38:57
fed into the brain via the vagus nerve
38:59
and so we know that if the vagus nerve
39:06
is blocked or damaged through injury
39:08
profound effects on appetite and eating
39:12
in fact it causes drastic weight loss so
39:15
it’s clearly a regulator of body weight
39:17
and vagus nerve stimulation by hormones
39:22
and neurotransmitters in the gut could
39:25
drive excessive eating behavior so over
39:27
stimulation is not necessarily good
39:29
thing and not surprisingly gut microbes
39:32
can actually regulate how much of these
39:34
neurotransmitters and hormones are
39:36
produced in the gut and they can
39:38
manipulate this to their own advantage
39:41
by producing things that can block or
39:43
stimulate the
39:45
consistent in the gut so microbes
39:47
control eating behavior by influence
39:49
signals that are delivered to the brain
39:51
and by the vagus nerve and two of the
39:54
most importance of dopamine and
39:56
serotonin so dopamine
39:58
associated rewards pleasure compulsions
40:02
serotonin regulates our mood our memory
40:05
sleep cognition dopamine about half of
40:10
the amount of dopamine producing the
40:11
body is produced in the gut and some gut
40:14
microbes can produce vast amounts of
40:17
dopamine and so you may know that L
40:21
dopamine is used to treat Parkinson’s
40:23
disease serotonin is even more striking
40:26
but virtually all the serotonin the body
40:28
is made in the gut and gut microbes
40:31
produce factors that can mimic or block
40:34
serotonin action in the gut and
40:37
deficiency of serotonin is linked to
40:39
depression so I hope you can see that
40:42
microbes by manipulating just these two
40:45
neurotransmitters can profoundly
40:47
influence our mood behavior whether
40:50
we’re anxious whether relaxed how much
40:52
we sleep how much we eat and so linking
40:58
this to a disease interest this is more
41:00
recent study now linking gut microbes to
41:02
a disease that’s called autism spectrum
41:06
disorder so autism so we know from
41:10
looking at patient’s microbiota is that
41:12
they they have they’re disturbed they
41:15
have alterations the makeup of microbes
41:17
and also there are altered levels of
41:20
what the microbes produce and there’s a
41:23
mouse here that can be can develop
41:26
autism like Syndrome particular
41:28
excessive grooming and vocalization is
41:32
affected as the art as it is in autistic
41:34
children and what this group that works
41:37
with this mouse showed that they could
41:39
restore or treat this mouse by using ant
41:42
probiotics so live bacteria and so the
41:47
live bacteria altered the gut
41:49
composition of the microbes and it
41:50
looked now more like normal animals and
41:53
this was linked to resealing of the gut
41:56
so these animals are leaking
41:58
and it was the leakiness allowing but
42:00
these microbe derived byproducts to get
42:03
into the bloodstream and into the brain
42:04
but as soon as the barrier was improved
42:07
the leakage stopped and it restored the
42:12
normal levels that you would find in
42:13
serum and it stopped or halted some of
42:17
the features of autism so this is animal
42:20
experimentation but it clearly shows
42:22
that it could be a role for alterations
42:25
in gut microbes that are linked to
42:26
neurodegenerative diseases and autism in
42:29
particular so neurotransmitters well
42:33
there are also hormones producing the
42:35
gut which regulate appetite and here
42:38
they said there are appetites that are
42:40
produced to say stop eating you’ve eaten
42:43
too much now we have all we need
42:45
no more tweet and then there are
42:47
hormones it’s signals to the brain state
42:49
we’re hungry you need to eat and it’s
42:52
the balance of these two that determine
42:55
our appetite regulates how much we eat
42:58
when we eat not surprisingly now perhaps
43:01
you think what gut bacteria can alter
43:04
the balance of these hormones and these
43:08
hormones are mainly produced in the gut
43:10
so we know that probiotic bacteria can
43:13
raise the level of this amino acid
43:16
tryptophan and tryptophan is an
43:18
important because it’s involved in
43:20
generating or producing these hormones
43:22
and bacteria that live in the gut can
43:26
produce mimics of some of these hormones
43:30
in for example leptin graylien pyy that
43:35
are influenced your appetite so they can
43:39
influence eating and appetite control
43:41
directly by mimicking the hormones
43:43
normally produced in the gut
43:45
indirectly they can stimulate things
43:47
that will block hormone signaling to
43:50
change your appetite and this is a
43:55
slightly different one this is very
43:57
recent showing how we with this
44:00
information we can actually use it to
44:02
try and redress the balance so here we
44:07
have this chemical here which is
44:09
produced as a result of a break
44:11
digestion of fats is called napes and as
44:15
I said these are naturally producing the
44:16
small bowel as a process of digestion
44:18
lipid digestion obese individuals have
44:22
very low levels compared to normal
44:24
healthy individuals and so what this
44:28
group said well okay what if we engineer
44:30
a bacteria that lives in the gut to
44:31
produce this factor can we then reboot
44:35
increase the levels back to normal and
44:39
so what they show is when they fed these
44:40
bacteria producing this chemical to mice
44:43
you could protect them from becoming
44:45
obese so give them a high fat diet given
44:47
lots of Big Macs
44:48
they stayed lean just by giving bacteria
44:52
that produced this chemical and what’s
44:55
interesting is this persisted for a very
44:58
long time even after the bacteria to
45:00
left the body there was still in effect
45:02
so obviously this could lead to a
45:06
different type of intervention using
45:08
these engineered bacteria as a treatment
45:12
for redressing appetite control and
45:14
maybe even obesity so gut microbes you
45:18
know we can engineer them and we can
45:20
utilize our expertise in work with
45:22
microbes for beneficial effects and you
45:26
know I’ve tried to highlight one or two
45:28
things that microbes produce that
45:29
influence our behavior this is a little
45:31
bit more of a list that shows things
45:33
that impact on our body’s function I’ve
45:36
talked about energy metabolism the
45:38
equity’s factors that help is blood clot
45:40
blood for blood coagulation new
45:43
adjustments I talked about that sleep
45:46
and mood they produce factors that will
45:48
determine how much sleep we take whether
45:50
or not sleeps beneficial and it’s just
45:53
they produce factors that cause bad
45:54
breath so a variety of things that
45:56
impact on our health and behavior so I
46:00
come to the third prediction that there
46:04
is a positive selection system positive
46:07
reinforcement if you like in which the
46:10
type of food we eat selects for specific
46:12
microbes which in turn then feedback on
46:15
making us eat more of that and my
46:18
example here is a seaweed diet so a
46:22
stable diet selects a microbial
46:24
specialists the
46:25
lead to us wanting to eat more of these
46:27
things so there’s two types of seaweed
46:29
Dyer this is one but I’m not going to
46:32
talk about that one I’m going to talk
46:36
about this one okay seaweed now Japanese
46:42
in in Japan vast amounts of seaweed are
46:46
consumed every year about more than four
46:48
kilograms per person but they can
46:52
process and eat seaweed because they
46:55
have genes present in their microbes
46:58
that produce the enzymes that allow them
47:00
to break down the seaweed okay the genes
47:04
originated from bacteria that live on
47:06
the seaweed so as they were consuming
47:09
the seaweed some of those microbes
47:12
stayed in the gut long enough to pass on
47:14
these genes to the normal population of
47:17
microbes in the gut so this microbes
47:22
that contaminated seaweed actually
47:24
transferred some of the beneficial
47:26
enzymes and genes they had to the normal
47:29
population migra’s in their gut so this
47:31
is positive reinforcement because
47:33
seaweed has lots of health benefits the
47:36
exacta fication promotes weight loss
47:38
lowers blood cholesterol so the helps
47:41
reasons to eat it and the more you eat
47:43
the more microbes and genes you have you
47:47
acquire enable you to break it down and
47:49
get maximal nutritional benefit so it’s
47:51
is positive reinforcement but you can
47:54
only do that if you have the microbes
47:57
there and the genes present in the first
47:58
place Japanese population do because
48:02
they consume a lot of that so as another
48:05
type of food preference which is food
48:07
avoidance and food allergy okay
48:10
so food allergies have increased
48:12
dramatically in recent times so more
48:16
than 50% since 1997 and they’ve been
48:19
linked to the modern lifestyle so-called
48:22
hygiene hypothesis overuse of
48:24
antibiotics again destroying of the
48:27
microbiota and so we can sort of look at
48:30
this in more detail using again mice and
48:33
so if we destroy the microbiota in mice
48:35
with antibiotics we can actually
48:38
lick give these mice analogy to peanuts
48:41
just as many children have but if we
48:44
reintroduce one type of bacteria into
48:46
the gut we can actually cure them of
48:48
their allergy and that’s this bacteria
48:50
Clostridium so this is direct evidence
48:53
linking gut microbe activity to food
48:56
avoidance okay and food allergies so not
49:01
only are the microbes that will
49:02
encourage us to eat more there are
49:04
microbes in our gut that will stop us
49:06
from eating things which causes harm
49:08
smart bugs
49:10
really and also sweetness and taste
49:13
again if you look at taste receptors
49:16
that are present on the tongue germ-free
49:19
mice have different types of receptors
49:20
compared to mice that have populated the
49:22
microbes so Joffrey mice have a sweet
49:26
tooth they prefer more sweets and have
49:28
lots more sweet receptors on their
49:30
tongues than mice that have populations
49:35
of michaeles in their gut and so near is
49:37
the knowledge on come to in humans is
49:39
patients that undergo gastric bypass
49:41
surgery for obesity their food
49:44
preference is shift enormously in fact
49:47
they develop avoidance strategies to
49:49
stop eating like some dairy products and
49:51
even meat and this is a company by
49:54
striking change than they got microbes
49:56
as a result of the surgery so microbes
50:00
can influence food preferences by
50:02
altering our taste perception of foods
50:05
so all of this together is summarized
50:09
here so what I’m predicting is that food
50:12
cravings are associated with vagal nerve
50:14
stimulation by blocking that we control
50:17
appetite and we can reduce food cravings
50:20
by altering our gut microbes we can cure
50:24
food cravings and we can cure maybe
50:27
allergies and then the diversity of our
50:31
gut microbiota and what they produce
50:33
should affect food choices and satiety
50:36
okay so if we increase the diversity we
50:39
have a better chance of controlling
50:41
appetite and keeping us healthy and not
50:43
from gaining excessive weight so that’s
50:47
great so how do we actually go about
50:50
changing the
50:51
that live in our gut so this is gut
50:54
microbe therapy which I’m leading to
50:55
lawn care so anything or when’s it going
50:57
to talk about lawn care that’s coming
51:00
right so message to fix your brain you
51:04
need to fix your gut and there are
51:07
different strategies we can use there’s
51:09
the expensive one pharmacy prescription
51:12
of drugs sorry getting a bit ahead of
51:15
ourselves here
51:18
antimicrobial therapy so obviously I’ve
51:21
highlighted some of the issues with
51:23
antimicrobial therapy toxicity can cause
51:27
the outgrowth of pathogens like cross
51:29
stream difficile and we develop
51:32
resistance our bugs would develop
51:33
resistance to the antibiotics and
51:35
they’re not cheap vancomycin however has
51:38
been used for diet induced obesity to
51:40
control diet in use to be so it’s not
51:42
all bad news
51:43
but it’s still expensive other
51:45
approaches rely on biotics Pro and
51:48
prebiotics and then I’m going to talk
51:50
about transplants I there we go I will
51:55
do probiotics there we go live
51:58
microorganisms which when administered
52:01
in adequate amounts confer a health
52:02
benefit that is the w-h-o definition of
52:05
a probiotic they are found in a variety
52:08
of foods these will be most familiar to
52:10
you these are generally for anybody then
52:15
we have ones that are designed for
52:16
children and even pets so you can get
52:19
probiotic to your pets evidence that
52:24
they work or may work so there’s
52:26
evidence that they can decrease food
52:28
intake they can reduce fat mass improve
52:31
insulin sensitivity stop us from
52:33
becoming diabetic yogurt is the food
52:37
that’s most associated with reduce
52:38
weight gain if you think of the things
52:40
that we eat to try and reduce our weight
52:42
yogurt is one of the things we generally
52:44
eat and probiotic treatment in pregnancy
52:48
can prevent excessive weight gain in the
52:51
infant after birth so the other approach
52:55
is prebiotics and prebiotics can be
52:57
suited as food to feed your healthy
53:00
microbes
53:01
and if you go remember back to my gut
53:03
trivia slide I said you need to consume
53:05
50 or 60 grams and these things well
53:08
this is what I’m talking about
53:10
these are the types of food that I will
53:13
fuel provide the fuel for your healthy
53:15
bacteria and there can be in lots of
53:18
things from pre-burn even toothpaste
53:20
contain probiotics prebiotics food for
53:24
your gut bacteria so this is what they
53:26
are generally as I said the different
53:28
types of sugars breast milk is a very
53:31
good source of inulin which is a very
53:33
good prebiotic and then these variety of
53:36
foods here
53:38
but five a day this is one of the reason
53:42
why we keep saying five servings of
53:44
fruit and vegetables a day there are
53:46
very good source of prebiotics to keep
53:48
your gut bugs healthy okay so you can
53:52
take probiotics and you can feed your
53:55
healthy bugs by eating these types of
53:57
foods the more radical approach is okay
54:01
that’s not working let’s get rid of
54:03
everything and replace it so fecal
54:07
microbiota transplantation so this is it
54:11
in a snapshot
54:16
and maybe I’ll cure me a my food
54:18
addiction yeah sounds gross
54:21
God how the hell could this work but it
54:23
does work it works incredibly well for
54:27
treating gut infection against C
54:28
difficile to come up again you know it’s
54:31
a 94 percent cure rate which is much
54:33
much higher than all the drugs and
54:34
antibiotics sounds gross but it works so
54:38
the question why does it work and how
54:40
does it work well that’s something the
54:42
Institute we’re very interested in
54:43
knowing so it works but you might think
54:46
well this is something new I’ve only
54:47
been reading in the Daily Mail for the
54:49
last year or so but in fact it goes back
54:52
a long long way the Chinese were way
54:54
ahead of us so two and a half thousand
54:57
years ago they were giving people yellow
54:58
soup to drink to keep them healthy vets
55:01
have been using it for a couple hundred
55:04
years a post called transformation
55:07
transferring stool from one animal to
55:10
another to keep it healthy first really
55:13
use tested in humans in 1958 it was
55:17
given to four patients there were near
55:19
death from a type of colitis it cured
55:22
all four patients and then since the C
55:25
difficile experiment you know we’ve
55:27
treated over 500 patients no side
55:31
effects whatsoever and success rate is
55:34
incredibly high and it’s stable so as
55:37
far as five years out you know these
55:39
people are still free of Clostridium
55:41
difficile infection so it is very good
55:44
so how do we do it there are several
55:47
options okay there’s the craps you’ll
55:53
there’s you know things you can have
55:56
it’s part of your healthy diet for
55:59
there’s the very more unpleasant way a
56:02
tube and if you go on the internet you
56:05
can get do DIY kits that allow you to do
56:07
this at home
56:08
very scary stuff but you know I think
56:11
we’d all prefer the crap show so what
56:14
are we going to use it for so I’ve said
56:16
you know there’s some obvious diseases
56:17
obesity clearly I’ve shown giving you
56:20
some evidence that got microbes cause
56:22
obesity so if we change our gut microbes
56:24
can we stop us from becoming obese or
56:26
even cause weight loss eating disorders
56:29
again
56:30
showed it as a link between our gut
56:32
microbes and what we eat or what we
56:34
can’t eat so again this could be another
56:36
application autoimmune diseases
56:38
inflammatory bowel disease Crohn’s
56:41
disease ulcerative colitis rheumatoid
56:44
arthritis they’re all potential slightly
56:46
more speculative but something we’re
56:48
interested at the Institute in looking
56:49
at can we reverse some of the effects of
56:51
aging ooh not quite sure what that is
56:59
now I don’t want BT burned so yes can we
57:05
reverse the effects of aging so our gut
57:07
microbes change drastically as we age
57:10
and that’s the search of a decline in
57:12
our immune system function we become
57:14
less resistant to infections and we
57:18
mostly some people here probably annual
57:20
flu vaccines right try and boost our
57:22
immunity
57:23
what if we could boost your immunity by
57:25
giving you a crap seal would you rather
57:28
have a needle or a corruption maybe
57:32
maybe we can reverse other signs of
57:34
aging you know maybe ifr we’re rich and
57:37
famous because we’ve got the youth
57:39
capsule yeah Reggie’s taking orders at
57:43
the frontier
57:45
how does it work well this is another
57:48
example of how it works so this is fecal
57:50
microbiota transplant by a nasal gastric
57:52
tube so this is you know the way it’s
57:54
been working so far taking my crinkle
57:57
micros from lean donors given to
57:59
patients with metabolic syndrome these
58:01
are patients at risk of developing
58:02
diabetes six weeks post treatment we can
58:06
clear glucose from the blood and they’re
58:08
now responding to insulin and this is
58:10
associated with a drastic change but
58:13
they got microbes increased diversity
58:16
but with everything that’s always a bunt
58:19
and this is the butt donor selection is
58:22
important this is a very reason a report
58:25
was published 32 year old female with a
58:29
recalcitrant C difficile infection
58:30
remember this is the disease we can cure
58:33
with FM t she decided she wanted to take
58:37
stool cell from her daughter as the
58:40
donor as you probably would a daughter
58:43
was a little overweight
58:44
but she later gained weight and became
58:47
obese the mother 16 months post
58:51
treatment have been given her daughter’s
58:54
microbes got microbes became obese she
59:00
gained excessive weight despite all
59:02
interventions she could not keep the
59:05
weight off and at 36 months she weighed
59:08
80 kilograms a BMI of 34.5 what this led
59:14
in this particular Hospital was a
59:15
complete change in the way donors are
59:17
selected okay so there is the smoking
59:21
gun here obviously the clinicians would
59:23
think well it came from the best patient
59:25
we just transferred the phenotype to the
59:27
mother well maybe but clear there’s a
59:29
link here so what we have to think about
59:31
carefully now is donor selection what is
59:33
the criteria we need to apply to a donor
59:36
in order to be able to use their stool
59:38
sample for a transplant here’s the lawn
59:43
care so if you think about trying to
59:47
keep your gut microbes healthy you know
59:48
here’s our healthy flourishing lon we
59:51
can devastate it with antibiotics you
59:54
know we can just let the weeds grow so
59:56
if we’ve got antibiotics
59:59
you know we might want to give
60:00
prebiotics you know turf food or we
60:04
might want to put new seed down
60:05
probiotics right and then the more
60:08
radical therapy a lawn transplant
60:11
bacterial therapy okay so think of your
60:14
gut
60:15
keeping Elvis lawn care and this is my
60:19
take-home message okay if you have young
60:23
children get them a pet and let them
60:26
roll around in the mud
60:27
let them eat mud you know maximum
60:30
exposure lots of healthy microbes and
60:34
with that I thank you and I’m happy to
60:36
take any questions you might have
60:37
thank you
60:47
you