Amazing Gut-Mind Link
Tackling depression and anxiety via the gut – the amazing story of how a sad mouse could change the treatment of mental health.
And how to keep your gut as happy as possible. Happiness expert Gretchen Rubin offers tips on how to be happy, even if you’re British.
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BBC voiceover:
BBC sounds music, radio, podcasts.
[Music plays]
Narrator:
This is the story of a sad mouse and a human who wanted to be happier. And the secrets of trillions of tiny, tiny organisms who shape our lives, our bodies, our minds, in ways we're just beginning to understand.
BBC voiceover:
From the BBC this is All Hail Kale, a discerning yet loving look at all things wellness with Tim Samuels.
[Musical introduction]
Narrator:
Act One: Words no mouse wants to hear.
Tim Samuels:
The human in this story may be me, it may be you. For now, we'll call him Tim. We find him lying on his couch, bingeing on the latest episode of Narcos Mexico. I, ahem, he, keeps missing bits of the dialogue though, as he's distracted by an aimless WhatsApp chat with a female human. Over in Canada, we find our mouse, let's call him Cedric, lying on his bed of straw, waiting for the food pellets to come through the bars of his home. He too lives alone, and like the human, it's by choice. That's how Cedric and his fellow BALB/c males prefer it. The human lies awake, ruminating over the same life decisions he should have made differently, trolling himself. At times, he finds it hard to just snap out of the low mood. It's not as if he's facing war or famine, but life seems pretty complex and hard to control these days.
ARCHIVE CLIP:
There's no happiness in the me me me world, there's only happiness in the ‘we’ world, you know, where we're serving each other.
Tim Samuels (voiceover):
He's been to talks, tried mindfulness, meditation, acupuncture, yoga, happy pills, vitamin pills, vomit-inducing herbal pills, psychotherapy, cranial sacral therapy. He recalls happiness guru Gretchen Rubin, telling him small thoughts and acts can make a big difference. Even if you're British.
Gretchen Rubin:
Think about gratitude. On my screensaver of my phone, I have a picture that kind of like fills me with happiness and warmth. The great thing about gratitude is first of all, it reminds us of everything that we have in our life that we're taking for granted, which is very easy to do, whether that's health or happiness or electricity or whatever. And also, gratitude tends to drive out negative emotions. If you think well why would I be grateful for my in-laws? Well, you can see when my in laws really supported us in the early days or their great grandparents or I have, you know, my sweetheart is a product of them has whatever I think of them now that's how I found my sweetheart, the good deeds we do for other people, then even the nice and considerate things that people do to help us. I think it's when people know they're like, oh, it's nice of you to hold the door open for me because you can see that I have my arms full. This can be things like setting people up on a date or making a business connection for people and they definitely do make you happier.
Tim Samuels (voiceover):
Cedric thinks he should feel a sense of gratitude, pride at being part of a long line, two hundred generations, of mice sacrificing themselves for medicine, not that they've had too much choice. As usual, though, Cedric feels anxious and keeps to the shadows, still wired for a swooping owl or a prowling cat, although he's never known anything but a cage in a lab and like all BALB/Cs, Cedric has a thing about steps. He did this at the top of the stairs connecting his bedroom to the lounge, minutes passed before he manages to scamper down. One paw forward, two back, the family motto.
[Music plays]
Tim Samuels (voiceover):
Back in London, an esteemed professor of genetic epidemiology at King's College is no longer scratching his head. For years, one question has been puzzling Tim Spector. How can identical twins be so different? One fat, the other thin, one happy, the other sad. It doesn't make sense. They have exactly the same genes. The brutalist 1970s building has no bath from which to leap. But Professor Spector is having his eureka moment. The differences between the twins is down to their guts.
Professor Tim Spector:
One of the biggest factors that came across was their microbes were different. That was the thing that got me into this particular area, realised that the potential for having such a big effect that could come from something that wasn't genetic, which meant that also, we had the power to change it. And that, for me, was a major moment in my career. You know, maybe there's these microbes which are really essentially a newly discovered organ.
Tim Samuels (voiceover):
Not far away, the human is wondering whether or not to send a “Hey, just checking, you got my email”, email, to a programme commissioner, a knowing charade that makes him feel as small as, well, a mouse. He could instead be celebrating that we now know there's a new organ in our bodies. Brain, heart, lungs, liver, meets the microbiome, a collective of 100 trillion micro organisms in the gut, two kilogrammes of bacteria, viruses and fungi, a whole other world that keeps us going.
Professor Tim Spector:
So we couldn't live without these microbes and when you deprive animals of them, they lose weight very fast. So the first thing they do is they're digesting our food. We only have about 20 digestive enzymes and these guys have thousands, tens of thousands of ways of breaking down the food in our guts into other nutrients. So we just wouldn't get the nutrients, we wouldn't get the calories from our food if we didn't have these guys, but they also convert a lot of the food that we get things like polyphenols, which we know are healthy for us used to be called antioxidants and every plant has these chemicals which are defence mechanisms. And we can't actually use this stuff at all, but the microbes use it. It's like rocket fuel for them. So when we eat berries or strawberries or nuts or seeds or coffee or dark chocolate or olive oil or red wine, we're getting this amazing range of chemicals which our microbes convert into other nutrients which then make sure the cells in our gut wall, our immune cells, are well fed and that keeps our immune system in tip top condition.
Tim Samuels (voiceover):
Cedric the sad mouse isn't thinking about his benevolent bacteria. He's getting over climbing the steps to reach his lunchtime pellets. Would he kill for a piece of cheese? would a nibble of edam be too much to ask for, a corner of Brie for his bucket list? his cheese dreams are suddenly interrupted, a rubber glove swoops in, drops Cedric in another cage, and then picks up some of Cedric's droppings. Hold on. That's not just his poop and what's that syringe for? What happens next is still too difficult, too shameful for Cedric to talk about but as the syringe enters the mouse's mouth, a professor of gastroenterology, Premysl Bercik could be heard describing what was happening in the McMaster University lab in Ontario.
Professor Premysl Bercik:
So this is actually taking the stool samples from the conventional mice and [putting] through the needle into their stomachs and if you wait for a period of two to three weeks the microbiota will be established in these recipient mice and then you can study their behaviour.
Tim Samuels (voiceover):
Words that no mouse wants to hear. Faecal microbial transplant. What on earth was this mad scientist playing at, talking about changing Cedric's behaviour, even his personality, by messing around with poop. And with that, Cedric can remember no more.
Narrator:
Act Two: A miserable month with no blueberries.
Tim Samuels (voiceover):
The morning started as it always did for Hank. He washed his whiskers, had a quick workout on the wheel then bounded down the steps. Hank was a happy mouse, a swiss mouse who never got involved in another mouse's conflict. Nothing fazed him. So when the rubber glove picked up some of Hank’s droppings he nonchalantly assumed even his poop merited research. When the glove plucked him out, he was braced for adventure, not for what happens next... The human was feeling drowsy after lunch. He'd not had an email back from the email chasing the other email, and when he'd seen on Facebook an ex was engaged it tipped him into the self-loathing of a cheese toastie made with white bread not even white sourdough, with lashings of lactose. Under bleached flour assault he sensed trillions of microbes turn distinctly less friendly. Whilst he clicked around sites, banging on about the gut minds link, about 90% of the body’s feel good chemical serotonin being based in the gut, and the vegus nerve being a major highway running directly between the brain and gut. Not that his stodgy mood was lifted by California nutritionists in tight t-shirts.
ARCHIVE CLIP:
Why do I get so excited about this? Because it proves, literally proves, that if you're not taking care of your gut and you're not taking the right measures to improve your gut health that you are not going to ever change your brain.
Tim Samuels (voiceover):
Fermentationists in terribly tidy kitchens.
ARCHIVE CLIP:
Depression, anxiety and negative emotions, in general, can be a sign that your body is missing the nutrients and the right mix of beneficial probiotics.
Tim Samuels (voiceover):
Or even doctors with supplements to sell.
Professor Premysl Bercik:
One of the things that is very important for you is to get your gut right so your brain can be right.
Tim Samuels (voiceover):
When the syringe appeared, Hank the happy Swiss mouse could only rue his family's lack of fighting experience. FMT, faecal microbial transplantation, was afoot. The poop from sad Cedric was being put into Hank’s stomach and Cedric was being given Hank’s droppings, their bacteria transferred into each other's guts. Professor Premysl Bercik would be monitoring both mice.
Tim Samuels:
So the hypothesis you're studying here is whether taking the gut bacteria from the confident mouse and through its stool sample, putting it into the shy mouse, whether that was going to affect the behaviour of the previously reserved mouse.
Professor Premysl Bercik:
Absolutely, you’re right.
Tim Samuels (voiceover):
Perhaps Cedric and Hank could take comfort that the same principle is already being used on humans. Across the St.Thomas's campus, where Professor Spector had made his twins breakthrough, Dr. Simon Goldenberg is poised with human poop for vulnerable patients with a C. difficile infection that won't respond to antibiotics, whose microbiomes need more good guys, from someone else to see off the C. diff.
Professor Tim Spector:
Yeah, so we have a bank of faecal transplant here at the hospital. So we have a group of donors, healthy donors who have been screened very robustly. So they donate their stool and then we store it, we bank in our minus 80 freezers so it's ready to be used whenever we have a patient. And essentially, it's the same processes when a patient has a colonoscopy. So camera tests have a look at the inside of the bowel. So the tube goes through the back passage into the bowel and then down one of the channels of the instrument, we flush through the faecal transplant.
Tim Samuels:
Okay. And what's the success rate?
Dr Tim Spector:
It's very good in that group of patients. So it's around about 80-85%. For patients who've had one faecal transplant, a small number of patients will have to have a second and that brings the success rate up to about 90 or 95%.
Tim Samuels
Okay, so lives have been saved?
Dr Tim Spector:
I think so. Yeah. I mean, this can be a really severe illness in some patients, particularly those who've got lots of other co-morbidities and illnesses. And you know, a general kind of mortality rate for patients whose C. difficile might be 10%. So, stopping that chain of infection, stopping that cycle of relapse and treatment for this group of difficult to treat patients can be life saving in some circumstances.
Tim Samuels (voiceover):
On his favourite streets in London, the human was having his guts probed back at the Harley Street Health Centre where the delightful Dr. Anam Abood once diagnosed lactose intolerance. He'd only ended up there after a highly unconventional doctor using a bizarre Russian machine told him his guts looks dodgy. It turns out the gut, without showing any warning signs, was indeed leaky, probably through ignoring the lactose intolerance.
Dr Enam Abood:
So the inside of your small intestine is inflamed and the inflammation makes absorption of nutrients difficult.
Tim Samuels:
So all the organic food I've been scrimping to buy, the healthy stuff, the juicing, straight through me because I've got an inflamed gut?
Dr Enam Abood:
Because you have an inflamed gut.
Tim Samuels:
Do you think this may have affected my moods, my energy, my mental well being?
Dr Enam Abood:
I actually believe so and I’ll tell you how that works. The gut flora, our good bacteria, 80% of our immune system is linked to it. It is responsible for 80% of our immunity. There are some elements of very important nutrition that are missing, then definitely we're not getting enough food, serotonin levels have dropped, endorphins are not enough and the effect of gut over mind, it is quite obvious and it is very logical then when it happens.
Tim Samuels (voiceover):
To turn the gut around, no sugar and no fruit for a whole month. But lots of probiotics. Further down Harley Street, he ran into a nutritionist he'd been hearing about, Marek Doyle.
Marek Doyle:
Let me be clear, I use probiotics all the time.
Tim Samuels (voiceover):
Who said to really let the good bacteria take back the gut you’d have to dig even deeper.
Marek Doyle:
And yet in my clinic if I see an individual and blindly give them probiotics, what tends to happen? Nothing.
Tim Samuels (voiceover):
Getting into mitochondria and adrenals.
Marek Doyle:
And it always comes down to the same issue. Will those probiotic species colonise your gut lining? If there's no space for them to colonise they won't. What's the big factor there? Have you successfully killed off their competition? That's a whole other story for another time. But for now, no bananas, no booze, not even a solitary blueberry for one miserable month. In the lab in Ontario, scene of the transplant, Cedric was also miserable and as anxious as ever. For the two weeks since, he barely left the shadows of the cage, hardly ventured downstairs. After the shock of it all, Hank had bounced back to his usual happy self, bounding around the house, railing against the snowflake BALB/C mice. Who can't tolerate a bit of minor experimentation. Maybe Cedric needs a safe space in his cage, he chuckles, a trigger warning for rubber gloves. He soon forgets all about the experiment. Maybe it'd been an Andrew Wakefield hypothesis or one of those placebos you hear about. Nope. Nothing has changed.
Narrator:
Act Three: Poop versus prozac.
Tim Samuels (voiceover):
Something is stirring in Cedric. In the third week after that fateful swap, he feels less anxious, more confident, more willing to explore. Steps are less daunting, shadows less enticing. One day, I might even be as big as Stuart Little, he dares to think. Strangely once happy-go-lucky Hank is also experiencing a transformation. There's a nervousness he's not used to, the world seems more daunting, the darkness comforting. Cedric and Hank were becoming each other.
Professor Premysl Bercik:
So the shy mice... usually take them around 280 seconds to to step down from the elevated platform after the faecal transplant, they were stepping down within two hundred seconds, so probably eighty seconds of difference. And conversely, the daring mice, the Swiss mice who usually were stepping down quickly around 20 seconds now which took them up to 60 seconds to step down. This was actually the first proof that changing the microbiota composition can directly impact behaviour profile of mice. And also now we have more and more data showing that it's not only the behaviour but also structure and chemistry of the brain.
Tim Samuels:
But just in terms of behaviour, I mean, is it, in human terms, a bit like if you're feeling a bit depressed or anxious and you get invited to a party and you don't want to go and you don't go… you know, in milestones, it would be actually you've gone from being anti-social to I'm going to go to the party I'm going to go, you know, I might stand... might leave early, might stand in the corner a bit, but I'm gonna go to this party.
Professor Premysl Bercik:
You can probably make these comparisons, yes.
Tim Samuels (voiceover):
An animal's behaviour, Its levels of confidence had been changed by the microbiome, rather than through brain chemistry, like traditional antidepressants. An archimedes moment for Professor Bercik, especially when he ran a follow on experiments, this time giving bacteria from humans with irritable bowels and anxiety to non-neurotic mice.
Professor Premysl Bercik:
Most surprising finding was that the mice that received the faecal transplant from patients with concomitant anxiety also displayed anxiety-like behaviour.
Tim Samuels:
Wow, so human bacteria can make a mouse anxious. When you got your results, did you sit around with your colleagues and just say this is incredible, you know, we have made a mammal more anxious or less anxious by playing around with the gut bacteria. Did it feel like a sort of new... whole new approach to treating mental health?
Professor Premysl Bercik:
Definitely, I think it opens completely new avenues for patients with psychiatric disorders. And again, I don't think that this applies to every patient with with anxiety or depression but in my opinion, there may be a subgroup of patients in whom these mental disorders are actually originating in the gut.
Tim Samuels (voiceover):
it's a lot for the human with sugar cravings and still unrequited emails to take in. That's a mouse's personality can be altered by a poop swap, not just from another mouse, but from a human too. Intriguing, amazing potential. Where though, is the evidence that human moods can be affected via the gut? Here, we crossed to a lab in Cork, where Professor John Cryan is feeling ever more vindicated. Neuroscientists don't often bother with below the neck, but for twenty years he's been focusing on the gut and stressing others out to see if a particular bacteria might be good for stress.
Professor John Cryan:
These were, you know, normal everyday people, but we brought them into the lab and we stressed them in the lab and we have good ways of doing that that are ethical. One of them is make people do public speaking tasks, the other is where they put their hand into an ice cold bucket of water, and someone is watching them and they feel very subconscious about how they're responding in this regard. So we've done a number of studies like that and much to our amazement that the people that were taking this bifidobacteria had a much reduced level of response compared to those that were taking a placebo. So that was really, really exciting and for us it was validation of our approach. It also was validation that we can take studies from animals and go all the way to humans and it will be interesting in the future if such strategies would also work in people who have high innate anxiety or are suffering from mild to moderate depression.
Tim Samuels:
So just by adding a strain of bacteria to someone's stomach that will reduce their stress levels?
Professor John Cryan:
We think it's acting lower down in the stomach. Yes, but it's either acting in the large or small intestine but that was sufficient.
Tim Samuels:
What was the name of the bacteria again which lowered stress?
Professor John Cryan:
It was a bifidobacteria along them. And in this case, this was 1714 was the substring.
Tim Samuels:
If you're prone to stress or low level depression is there any harm in giving it a whirl?
Professor John Cryan:
There's no harm but again the evidence hasn't looked at... there's no clinical studies of it in depression. All we've shown is that in unhealthy volunteers it dampens down the stress response. So we also need to be cautious about over-interpreting yet you know what I mean, but it is very promising... your genes you can't do much except blame your, you know, parents and grandparents, but your microbes, you can actually have some agency to try and modify them. I think what we're going to see in an era of precision medicine moving forward, you know, people will start to have their snapshot of what their microbiome looks like when they're healthy, and be able to see how that changes over time. And we could reach an era where physicians and healthcare providers in general are able to say, well, you know, you're losing some of these types of bacterial strains, it would be good to, you know, tailor your diet in a way or take this supplement to be able to boost that back and maintain health.
Tim Samuels (voiceover):
Somebody instantly ordered a packet of bifidobacterium longum 1714 and serotonin levels threatened to reach positively normal levels. After Professor Bercik the mouse-poop-puppeteer revealed his own probiotic breakthrough with a different strain around depression but rather than taking this to a pharmaceutical company...
Professor Premysl Bercik:
We joined our forces with, actually, Nestle Switzerland and the idea was to isolate a bacterium which can be beneficial in anxiety and depression and we have actually found a bacterium which is called bifidobacterium longum which in different animal models can treat anxiety-like behaviour and even some changes in the brain chemistry. It led us even to test it in patients. We targeted patients with irritable bowel syndrome and concomitant anxiety or depression and apart from monitoring their symptoms by questionnaires, we also did brain imaging which is called functional magnetic resonance imaging to see whether there are certain areas of the brain which are affected by this probiotic treatment.
Tim Samuels:
You've been road-testing a particular probiotic, which seems to show promising results with depression and anxiety and if the product comes out it's going to come out through Nestle who made breakfast cereal.
Professor Premysl Bercik:
Yes, this would be probably the best way how to take it so to combine yoghurt with this healthy probiotic bacteria and it probably... I can envisage that it's not only for really patients who are depressed or anxious but just to improve your mood overall. I mean, if you if you feel stressed, if you feel not very happy that day, maybe you can get that yoghurt and and improve your mood.
Tim Samuels (voiceover):
The human and perhaps others now wonders what to do until an even cheerier box of Cheerios launches. Or he can tell his therapist he's now seeing a pot of yoghurts on Fridays at four. From this tale of a mouse and the human prone to a particularly modern form of malaise, the gut appears to be yielding its secrets but maybe Western medicine today is merely catching up with what's long been known. In the fourth century, Chinese doctors were using yellow soup that contained dried or fermented humans stools to treat stomach upsets. Truly a fable for our times. Modern science revealing how modern life is taking a toll on our personal ecosystems.
Professor John Cryan:
In terms of genes, we are 99% microbial and these microbes were here long before humans were. So we've co-evolved. So all of the systems in our body have co-evolved always with microbial signals. And it is clear from studies where people have gone out in the field and looked at what the microbiome of people in Tanzania is, in hunter gatherer populations there, it's very diverse, really rich fibre diets. And then in our Western society, especially since the introduction of processed foods, the overuse of antibiotics, both by prescription and in the food chain are all having these negative effects on the microbiome and this may lead to some of the illnesses, the chronic lifestyle illnesses that we have. And a lot of work is going into this in inflammatory illnesses and obesity and metabolic syndromes but less has been shown in the context of brain health yet and so we need to do a lot more work to look at that.
Professor Premysl Bercik:
What you want is as many different fish in your fish tank or as many different flowers in your garden as possible. So whether it's a nut or a seed or a fruit, or you know, whichever part of the plant, each of those has different chemicals in it. And in fact, it's that diversity of the substrate that is giving these microbes the chance for even these rare species to actually flourish and that's something that no one's ever really discussed before in terms of optimal diets. And we'll be obsessed with calories or fat or sugar and these things just didn't matter because this was far more important than when you were vegan or vegetarian or carnivore or lactose free or whatever. It was just as diversity is the number one factor and of course there are factors. We know they like fermented foods, whether that's yoghurt, kefir, kombucha or sauerkraut, kimchi, and then increasing your fibre which is you will do naturally if you have lots of plants and avoiding processed foods with lots of chemicals, avoiding things like artificial sweeteners, avoiding emulsifiers. They're the things you can do, as well as going on farms getting dirty, kissing your dog. Lots of swapping microbes is generally good.
Tim Samuels (voiceover):
Or kiss a mouse. The human stands in front of some newly acquired glass jars and a squid-like pancake of yeast and bacteria working out how to produce kombucha. A task is so bewildering WhatsApp notifications have been silenced. Jars of kimchi and sauerkraut sits in the fridge, only one of which has already gone off. No-one knows for sure what happened to Cedric in the end but it's believed he went the way afforded to the most esteemed of lab mice to live out his days, down the cobbled steps of a Parisian street in a cheese shop.
Narrator:
And so our story ends, for now.
Today's show was written and presented by Tim Samuels. The production team was Nick Minter, Sera Baker, Ali Rezakhani, Roser Jorba Soler, Barney Roundtree from Reduced Listening and Gloria Abramoff. All Hail Kale is made by Tonic Productions for BBC Sounds.
