- Sam Mulrooney: Hello, everybody.

Welcome, welcome.

Thank you all for joining us here tonight.

This is Crossroads of Ideas, "Mindfulness and the Microbiome."

This is the third installment of our microbiome miniseries.

I'm Sam Mulrooney.

I'm the outreach program manager at WID and the director of the Wisconsin Science Festival.

And thank you all again for joining us here tonight.

Crossroads of Ideas is a collaboration between the Wisconsin Institute for Discovery, the Morgridge Institute for Research, and UW-Madison Strategic Communications.

It's an opportunity to foster dialogue between the community and UW-Madison researchers.

This series addresses issues that matter to our community and are the subject of research at UW-Madison.

Since 2014, Crossroads has been a staple of public programming here at the Discovery Building on UW-Madison's campus.

Now, tonight, we are here to explore the intricate connection between the microbiome and mindfulness, and the immense impact that they both have on our well-being.

So we have two truly outstanding researchers with us here tonight to help us conclude our miniseries, Dr.

Richard Davidson and Dr.

Jo Handelsman.

They will each take a few minutes to provide their insights, and then we'll finish with a shared conversation and make sure to save time at the end for audience Q&A.

But as a brief introduction to both of our presenters today, first, Dr.

Richard Davidson is the founder and director of the Center for Healthy Minds at UW-Madison, is best known for his groundbreaking work studying emotion and the brain, a friend and confidant of the Dalai Lama.

He is a highly sought-after expert and speaker, leading conversations on well-being on international stages, such as the World Economic Forum, where he served on the Global Council on Mental Health.

TIME magazine named Davidson one of the 100 most influential people in the world in 2006, and he was elected to the National Academy of Medicine in 2017.

And Dr.

Jo Handelsman is the director of the Wisconsin Institute for Discovery at UW-Madison, a Vilas Research Professor, and a Howard Hughes Medical Institute Professor.

She previously served as a science advisor to President Barack Obama, as the Associate Director for Science at the White House Office of Science and Technology Policy, where she served for three years until January 2017, and was on the faculty at the University of Wisconsin and Yale University before that.

She received the Presidential Award for Excellence in Science, Mathematics, and Engineering Mentoring from President Obama in 2011, and was inducted into the Academy, American Academy of Arts and Sciences in 2019.

So with that, please welcome first to the stage Dr.

Richard Davidson.

- Dr.

Richard Davidson: Thank you.

Thank you, Sam, appreciate it.

[audience applauding] Thank you so much.

And it's really an honor to be here because this is a celebration of a collaboration.

It's been a treasure for us to collaborate with Jo and her team.

And you'll hear more about it as we go along this evening.

But I, please don't expect me to say anything about the microbiome, because I'm very fortunate to collaborate with Jo, who is the expert.

I want to just spend a few minutes giving a very brief introduction to something that I'm very passionate about, and that is the possibility of scaling well-being.

And that will really be my theme this evening.

And let me begin by just showing an inspirational slide.

This was actually a slide that was taken-- a photograph that was taken in 2021 here on campus.

This was at the Waisman Center when the Dalai Lama was here for one of his 16 visits.

He has made more visits to Madison, Wisconsin, than any city outside of India under 500,000.

So we're very blessed to have had him on many occasions.

And we were showing him here how MRI works and how we can interrogate the structure and function of the human brain.

And he has been an inspiration to all of this work.

I want to spend just a few minutes on bad news.

There's so much bad news in the news, in the media.

I don't want to harp on this, but I do want to illustrate a couple of data points.

In the last administration, and under President Obama, we had an amazing Surgeon General of the United States, Vivek Murthy.

And in 2023, Vivek Murthy issued a health advisory on loneliness.

This is the first time that a public health officer of the United States called attention to loneliness as a serious public health issue.

And he had a few important data points in this report that I'd like to highlight.

If you look here, and I won't go through all of these details, but if you look in the figure in the upper left.

So this is looking at social isolation.

And what it shows is that-- And this is time that people spend alone over the past, roughly, 17 years.

This goes from 2003 to 2020.

There's been an increase of 24 hours per month in the time that people are spending alone.

This is a serious change in the social fabric of our lives.

If you look down in this figure, this shows social engagement with friends.

And this is showing a decrease of 20 hours per month in interaction with friends.

And one of the things that Vivek Murthy pointed out in this report is that loneliness actually exacts a greater toll on our physical health than smoking 15 cigarettes a day.

So these are data that was, that were in the report.

And what it shows is that lacking social connection is a greater risk factor for mortality than smoking 15 cigarettes a day.

And it's more than double the risk factor for premature mortality than obesity.

So this is a serious public health issue.

Now, how many of you have children?

Okay, most of you.

The next report that Vivek Murthy issued two weeks after this one was on social media and youth mental health.

And I won't go through much detail here.

I want to just bring your attention to one figure that was in this report.

And if you just pay attention to the bars on the right, these are representing comorbid psychopathology, which means a combination of anxiety and depression, as well as externalizing disorders like attention deficit hyperactivity disorder.

And what is presented is the prevalence of those disorders as a function of how much social media adolescents are consuming.

And what you see is that there's a linear increase in how bad things are as a function of the amount of social media that you are consuming.

The more social media that the kids are consuming, the worse their problems.

And the average teenager in the United States today spends 3.5 hours on social media.

That's not total screen time.

That's just the amount of screen time that's dedicated to social media.

One other data point that well-being matters, this is a study that was published a few years ago looking at the relationship between well-being and life expectancy across the world in 151 different countries.

And what you see is that, among, in countries where people are reporting higher levels of well-being, that is displayed on the x-axis here, people are living longer.

On the y-axis is life expectancy.

And the differences that are seen here are not trivial.

The differences between life expectancy in countries where people are reporting high levels of well-being, and countries where people are reporting low levels of well-being, are more than 20 years.

So these are enormous differences that are consequential.

So we've come to this really simple conclusion that is a very radical conclusion, that is that well-being can be learned.

Well-being is best regarded as a skill.

It's fundamentally no different than, in terms of skill acquisition, than learning to play the violin.

If you practice at it, you will get better.

And the amazing thing is, and this may sound really strange, particularly in today's world, but we humans are born to flourish.

And in fact, that is the title of my next book, Born to Flourish.

We are born to flourish, so it's easier to learn the skills of well-being than it is to learn to hate.

And in fact, that's almost a quote, this amazing quote from Nelson Mandela, who said something to the effect that we can learn to hate, but we can learn to love, because love is a more natural part of the human heart than is hate.

So... The same mechanisms that encode suffering, that include neuroplasticity and epigenetics, can be harnessed for the good and can be deployed to support enduring well-being.

And I just want to introduce you to a framework that we published a few years ago on the plasticity of well-being that holds that there are these four key pillars.

And I'm gonna go through this quite quickly now, just to give you a little taste of it.

The first pillar we call "awareness."

It's where mindfulness would be.

But mindfulness, in and of itself, is necessary, but it's not sufficient.

We also need connection.

Connection is about qualities important for healthy social relationships.

Qualities like appreciation and gratitude, kindness and compassion.

The third pillar is insight, and insight is about the narrative that we all have about ourselves.

We all carry around a narrative.

There are some people that have a very negative narrative.

They have low expectations of themselves and they have negative beliefs about themselves.

And what's important for well-being is not so much changing the narrative, but it's changing our relationship to the narrative so that we can see the narrative for what it is, a bunch of thoughts.

And finally, the last pillar of well-being is purpose.

And purpose is about staying motivated.

It's not about finding something more purposeful to do, but how can we find meaning and purpose in even the pedestrian activities of daily living?

Can washing the dishes or taking out the garbage be connected to your sense of purpose?

And of course it could be.

It just requires a little bit of reframing, something that can easily be taught.

So we've taken this framework and we've actually written a whole curriculum for it, and we've distributed it freely to the world in the form of an app called the Healthy Minds Program.

And any of you can download it wherever you get your apps.

This is some screenshots of the app.

You can go to the website, tryhealthyminds.org, to learn more about this.

The New York Times' Wirecutter has named this as one of the three best meditation apps for four years in a row.

The only one that's totally free, and the only one that actually is really evidence-based.

So what is some of the evidence?

Well, I'll just share a couple of things with you.

On the right is a study that we did here in Wisconsin with public school teachers, 662 public school teachers during COVID.

We gave them this well-being training where they learned skills of awareness, connection, insight, and purpose, and they did this for one month.

Five minutes a day for one month.

That's it.

The actual average time was slightly less than five minutes a day.

And they showed-- HMP stands for Healthy Minds Program.

That's the meditation intervention.

The WL stands for weightless control.

These were randomly assigned.

And you can see that on this measure of distress, which is a combination of depression, anxiety, and stress, they're showing dramatic reductions that persist at several months post-intervention.

And this is just five minutes a day.

We've subsequently replicated this with a better control group in Louisville, Kentucky.

Those data are presented here.

And one of the cool things we did in Louisville, which we weren't able to do here in Madison, is we actually got data on the kids.

And we asked the simple question whether children, students who are taught by teachers, who are randomly assigned to this well-being training perform better than students who are taught by teachers randomly assigned to a control group.

And I won't bore you with the details, but we-- This is kind of the Holy Grail.

And we found a signal that is really quite extraordinary, that's highly significant, where, and this is in a sample of around 17,000 children.

We found that these, the kids who are taught by teachers who are randomly assigned to the well-being training, perform significantly better on standardized math exams compared to their counterparts who were taught by teachers randomly assigned to a control group.

So when a teacher comes into class and shows up and is fully present, connected to their students with a sense of purpose, the students learn better and they perform better.

I want to end with this one study that Jo and I are involved with together.

Maybe she can share a little bit about the microbiome data for this study.

I don't have a slide of that.

And this is a study that uses the same intervention with a nationally recruited sample of depressed patients.

And we... The details here are not that important, but what we see, and these are patients who have a formal clinical diagnosis of depression using the gold standard.

And we see that these individuals-- In the red is the Healthy Minds Program.

The green is a very robust control group, where they get the Healthy Minds Program, but without any meditation instruction.

They get all the didactic information.

They receive these mini-podcasts, but they don't actually get the meditation itself.

And you can see that actually does incredibly well.

And the UC is the untreated controls, the group in blue.

Depression is decreased.

We also, this is a measure of anxiety, and on a measure of flourishing, they are doing better.

And we had people prick their fingers and put the drop of blood on a paper blot from which we can extract all kinds of information, and they send these paper blots back to us, and we can analyze the crap out of this.

And so one of the things we look at is measures of inflammation, markers of inflammation.

And IL-6 is a pro-inflammatory cytokine.

And these are data just hot off the press.

We literally got them a few days ago.

And it turns out that the group receiving the meditation training shows a significant reduction in this inflammatory marker over the course of three months, from before the intervention to three months after the intervention, compared to the control, the untreated control group.

So this is the first time we've seen a biological signal with just this minimal intervention.

Again, people are practicing, on average, approximately five minutes a day.

So let me end by just saying that we consider this an urgent public health need.

And our aspiration is to scale this massively, because I think everyone would agree that the world is falling apart.

And this is really our plan for the next few years.

And the microbiome work is incredibly exciting to us.

It's always been a mystery to me why there are roughly 200 million neurons in the human gut.

They must be doing something.

And we know that there is intimate gut-brain interaction.

And so it's been really exciting for us to be able to explore this for the first time.

So join us on this journey by nourishing your mind.

And through that, we can change the world.

And let me end with this quote from the Dalai Lama who said, "The systematic training of the mind, "the cultivation of happiness, the genuine inner transformation "by deliberately selecting and focusing "on positive mental states "and challenging negative mental states, "is possible because of the very structure "and function of the brain.

"But the wiring in our brains is not static, "not irrevocably fixed.

Our brains are also adaptable."

Thank you very much.

[audience applauding] - Jo Handelsman: Well, thank you, Richie, and thank you all for being here.

It's always hard to follow Richie in a talk.

One of my favorite speakers.

I'm gonna continue on the theme of well-being, and I'm gonna talk about a study that is part of the BeWell study, which Richie just showed us some of the data from.

This is work that I've been doing for the last few years, since, I think, right before COVID.

We started working together with Richie's lab, Simon Goldberg's group, and my postdoc, Margaret Thairu, is responsible for most of the data.

Here we go.

So I wanted to start with, why did we originally start thinking that the microbiome might have anything to do with the brain or mood?

And Richie just gave you a couple of hints that we know that serotonin, which is considered the happiness hormone.

It's neurotransmitter that is really important for mood.

It, we know that bacteria, certain bacteria, can make analogs or similar kinds of molecules to serotonin.

So it didn't seem like a, too much of a stretch that maybe there are bacteria in the gut producing serotonin.

But even more interesting is that 90% of the serotonin receptors, the things in the human body that bind and respond to serotonin, are actually in the gut.

So these bacteria are associating with or interacting with our serotonin receptors.

Other people had shown that there were different compositions of microbiomes in healthy people and depressed people.

Usually small samples, so small populations.

But it did show a difference.

And then the really dramatic study was one in Ireland, and it, this has only been done in Ireland.

We want to be the first ones to do this in the Americas.

They took the microbiome from depressed people and put it into rats, and the rats developed depression-like symptoms.

If you want to see a depressed rat, I can do an imitation later.

[audience chuckles] That was the most remarkable evidence for causality that, in fact, the microbiome is not just a byproduct of mood, but, in fact, it's having an influence on mood and behavior.

And so we set out to begin to look at, in the BeWell study, which is this very large national study that Richie's group developed.

It has well over 1,000 people total.

So it's gonna be the largest microbiome and mood study done.

And we wanted to ask two questions.

And first, does the Healthy Minds app, which I hope everybody has pulled up on their phones by now and started using, change the gut microbiome?

So, radical idea.

And, frankly, none of us, I think, believed that it was actually gonna pan out.

And then, could we replicate some of the work that had been done on much smaller populations, showing that microbiomes in healthy and depressed people differ?

So the structure of the study was to use the three groups that Richie introduced you to: HMP Full, where they're doing the short lectures, a few minutes of lecture and then a few minutes of meditation practice.

The HMP Active, we used to call it the active control, but it's clearly not a control, based on the mood data that Richie showed and some of what I'll show you.

It's not truly like you would think if they, if we showed them a sailing video or something like that.

And then just Usual Care people, who weren't subjected to anything on the app.

And we started out with measurements of their depression level and then took microbiome samples before and after.

And so we had matched samples for all of the people that I'll tell you about.

And so for the HMP Full, we ended up with 318 participants who had before and after.

So these are people that listened to these short lectures, which by the way, are fabulous.

There's a whole group of women in WID that go to sleep at night listening to this five-minute lecture given by one of Richie's colleagues named Cort, because they love his voice so much, and it's such an interesting set of lectures.

I thought they would keep me awake, but, in fact, I don't know why, they put me to sleep.

And one of the best parts that does not put me to sleep is he does interviews with Richie in many of the episodes, and so you get to learn the actual research that is underpinning a lot of what the app teaches you.

So that's the HMP Full, where you have both.

And the other is the didactic only.

So listening to Cort or one of the other voices just talk about the science of meditation and how people have learned what it does to the mind and the body.

And that group, the so-called control group, had 307 participants.

And then we have the Usual Care group, which aren't being, they have no intervention at all.

And so, what was remarkable was when we started asking first, what organisms are there?

So that was the first way to characterize the microbiome.

Just ask, what's the composition of the community of microbes in the gut?

And so the 16S rRNA, if anyone's interested, is the basis for deciding who's there.

So these are genes that act as a signature for different microbial species.

Every species has its own signature, and we don't have to culture the organisms in order to obtain that gene.

We can just amplify it out of the entire mix, which is really important because not all bacteria in the gut grow in our culture mixes.

So we want to look at the entire microbiome, not just the ones that grow.

And so, we follow the 16S collection.

And you may see or hear me mention ASVs, which are amplicon sequence variants.

And that's just because microbiologists can't decide what a species is.

So we call these groups, these just general taxa, the unit of study, because we don't want to call them strains or species, because we're not really sure what that means in microbial land.

And so, these are examples here of the Usual Care, the HMP Active, and the HMP Full, and each line in here is a different organism, different group of organisms.

And you don't have to read the organisms, 'cause I know you can't.

But the ones that are dark have gone up over the study, and the ones that are green have gone down over the course of the study.

And you can immediately see that these differ.

Just which organisms are there, which ones went up and which ones went down.

And so, one of the summary items that we found was this group of organisms.

So this is at the family level.

So a very large group, Lachnospiraceae.

Not a very well-known group of bacteria, but they are dramatically different, and they are higher in less depressed people, which means they were higher in people after using the intervention.

So that was really intriguing.

And then the one that I really like is a dramatic decrease in one of the bacteria, Blautia, which is a genus of bacteria that have been associated, historically, with studies of depression.

So these are associated with the negative mood.

So the HMP Full had the effect you might expect, to increase the good bacteria that make people seem to be happy, and decrease the ones that cause depression.

So, of course, there's a lot more to study in this.

We don't know much more than I'm telling you right now.

But those are the changes that we see.

One of the things that struck us is that, as Richie showed you, the depression scores go down even in the control population, the active control, who are just listening to these short lectures.

And we see microbiome changes, but they're not quite as dramatic and not as statistically significant as the changes we see with HMP Full.

So that's just an important piece.

Another element of what we see is that the HMP Full and HMP Active both cause an increase in butyrate producers, and I'll tell you what that means in a minute.

And there are two groups that do that, three ASVs within the Anaerobutyricum, and then the Ruminococcus also produce butyric acid.

So, I'll come back to butyrate in a second.

So first of all, taxa that were previously associated with depression have behaved as we might have predicted if we believed that meditation would affect people's mood and the microbiome was partly responsible.

And so this is just a comparison here of HMP Active, so the active control and the HMP Full, which allows us to emphasize the really big differences, the before-and-after differences.

And you can see that in terms of the big differences, HMP Full definitely has a larger effect.

And HMP Active, so the control, did not show a decrease of some of the negatively associated bacteria, bacteria that have been associated more with depression.

So we think there's pretty good evidence from this that in what, to date, is the largest microbiome study of the association of microbiome and mood, and the first that looks at a large-scale intervention like this with meditation, shows that, in fact, we do see changes in the microbiome.

And from these data alone, we can't say whether the bacteria are changing because of meditation and thereby changing the mood, or the mood is changing, and therefore, the bacteria are changing.

We can say that based on the previous rat study, but these studies don't separate that yet, so we're hoping that we'll be able to separate those later.

And so after the intervention, we have fewer of the so-called "bad bacteria" associated with depression.

And that's particularly noticeable in the HMP Full, where people are doing both a little lecture and a practice.

And there are more taxa associated with butyrate production.

So why do we keep talking about butyrate?

Butyrate has long been studied as a very important part of the gut microbiome.

So bacteria produce butyrate by fermenting dietary fiber.

Fiber is the content from our food that we can't digest ourselves.

And it's the bacteria that can usually digest that fiber.

And the process of digesting yields byproducts.

So, fermentation, you're probably familiar with alcohol fermentation, for example.

That's a byproduct that the bacteria or fungi produce in the process of fermenting.

These bacteria produce butyric acid as a result of growing on the fiber, and butyrate provides the really important source of energy.

It's the favored energy source for epithelial cells, or cells that line the esophagus and the colon.

In fact, when you feed someone butyrate, you can't even find it getting to their gut because the epithelium, the surface cells all the way down the alimentary canal, just suck it up.

They absolutely love butyrate.

So when there's enough butyrate in the gut, the lining of the colon becomes much more robust.

The cells grow, they divide, and you get very snug junctions between the cells that line the gut.

And so one of the theories is that butyrate seals the gut, that because the cells lining the gut become much more active, they're actually closing any holes in the gut that might allow organisms or chemicals from those organisms to get out.

So we know that butyrate is really important for maintaining the integrity of the gut wall.

Why that's important for depression, there are a lot of interesting theories.

One is that the bacteria themselves might escape from the gut and go toward the brain or something, somewhere else in the body.

But probably more likely is that the bacteria slough off parts of their cells that cause inflammation and other reactions, and thereby stimulate a negative response.

The other nice thing about butyrate is that it directly causes a reduction in inflammation, and inflammation has been associated repeatedly, gut inflammation specifically has been associated with depression.

So some of our next steps, we can talk about this more if people are interested, is culturing some of the organisms that are associated either with the depressed or the healthy state.

Develop a mouse model.

So we might go to rats if we can't repeat what the Irish group did with mice.

But mice are easier than rats, and they do get depressed, apparently.

So we will see whether we can take a mouse model, introduce some of the gut microbiome samples from our most depressed people and our most healthy people, and then see if we see mood changes in the mice.

And then finally, you know, in the long term, can we culture these organisms that are responsible and turn them into probiotics?

So I know I'm gonna get questions about probiotics, 'cause I think I've heard a question of what probiotics should we be taking after each of these microbiome talks.

These are just a few examples, and I am not an expert and I'm not a doctor, so I'm not recommending anybody take these.

I'm just giving you examples of the kinds of studies.

And it used to be that microbiologists kind of scoffed at probiotics 'cause they were used very broadly long before we had any data to support them.

Now we're developing enough data to be able to discriminate between the ones that actually do something and the ones that are just useless and a waste of your money.

So one study that I thought was really helpful was, it's an overview of all the probiotic trials that have been done in humans.

And so it tells you which ones gave an effect and which ones didn't.

And then similarly, a meta analysis, which is collecting all the trials in an area, looking specifically at probiotics and depression, and there are several studies that gave significant effects.

One that's really interesting showed that there's a probiotic they used that changed cortisol, which is that stress hormone that Richie mentioned.

And it also changed gut dysfunction in rats that have dysfunctional guts.

These are actually rat pups, baby rats that are stressed because they've been taken away from their mothers.

And that causes gut dysfunction and the stress hormone to be released.

And there's a probiotic that seemed to reduce that.

So that's one, you know, we're not rats.

We don't probably want to take that one until it's been tested on humans, but it certainly gives a pretty good hint that something is going on with these probiotics.

And then there was one that is unfortunately not big enough to really, in my opinion, rely on.

But they used 21 people taking the probiotic and 26 people taking a placebo, and they looked at the effect of taking the probiotic on mood, on the microbiome, and then they did neural imaging, and they saw brain changes.

So, with the probiotic.

So, these are just examples of the kind of work that's out there.

I don't think we're quite ready for recommendations of what probiotics are good or bad to take.

But I think we're getting really close.

So if people want to talk about that more, I'm happy to, but I won't give you recommendations.

[chuckling] But, except about diet.

We can talk about diet, which I think is a really safe thing to give recommendations about.

But I'll stop there and I'll ask Richie to come back up.

[audience applauding] So, Richie, I was wondering if you would go back in history, and if you don't wanna do this, we'll just go on to the next question.

You gave a talk about 20 years ago about your Promega study, and I thought it was one of the most life-changing experiences I had ever had.

And it was about a study where you trained people very rigorously in person-- so it wasn't like the app, the app is much easier-- in meditation.

And then you saw some pretty dramatic effects.

And I remember you specifically saying, "We chose type-A people out at Promega."

[chuckling] And I was wondering if you would just say a few words about that study and what you found.

- Richard: Yeah, that study actually was published in 2003, and it's my most highly-cited scientific paper, and also a paper that is probably the least rigorous science that I've done, to be really honest.

It had a very small sample size.

You know, it was very early on in this kind of work.

So, but it was an important start.

But what we did is we went to Promega, and we used Promega employees.

And Bill Linton, the CEO of Promega, was very supportive of us doing it there.

And we randomly assigned these employees to eight weeks of mindfulness meditation training or a control group.

And we measured their brain with brain electrical measures.

This was really before the days of MRI.

So it was really early on.

And the other thing that we did, which received a lot of attention, was the study was done, it was started at the beginning of September.

So two months was, it ended just before Thanksgiving.

And that's the time when people get flu shots.

So we gave everyone, at the end of the study, we told them, "Please don't get your regular flu shot.

"We're gonna give you a flu shot, "and we're gonna take blood samples before and after you get your flu shot."

And from those blood samples, we can determine how effective the vaccine is by actually measuring the antibody titers to the vaccine.

It's a measure of the extent to which the vaccine is, quote, "working."

And what we found is that the people who are randomly assigned to the meditation training actually had a significantly greater antibody response to the flu vaccine.

So it means that if they were exposed to the same level of the flu virus, the folks who went through the meditation training would be less likely to succumb to the virus or have, perhaps, a less severe case.

And what was really amazing was that the extent to which they showed the antibody response to the vaccine was correlated with the change in their brain activity.

So that was the very first randomized controlled trial that had ever been done of a mindfulness meditation intervention.

And so that, I think, helped usher in a new era of research in this whole area.

- Jo: I think 'cause of the biological measurements, both the flu vaccine and the immunology, as well as the looking at the neural imaging, I think that really changed the field, 'cause for a long time, sure, everybody has had this sense in the past.

It was seen, you know, meditation was seen as kind of fluffy and fringe and something that monks did, but maybe it wasn't really mainstream.

And I think this turned it into a science.

I mean, you've turned it into a science.

Do you want to talk about that evolution from your early days and the attitudes about meditation forty years ago versus now?

- Richard: Sure, yeah.

I developed an interest in meditation when I was in graduate school, actually.

And I schlepped my wife, before we were married, to our first meditation retreat-- Susan is here now-- in India in 1974 in the really beginning days of this.

And I was attracted to meditation because, really, I met people whose demeanor was really attractive to me.

And pardon me for saying this, if any of you are from the university, but these were folks that were not my professors in graduate school, but they were people on the outside who just were really friendly, warmhearted, kind.

They were the kind of people I wanted to be around, and I wanted to know more about their secret sauce.

And they all were meditators.

And so that led me on this journey.

And I came back from India with this fervent passion to do research on meditation.

This was in graduate school at Harvard.

And I came back, and my professors told me, "Richie, if you want a successful career in science, "this is a terrible way for you to begin... [laughter] "...and you'd better find something else to study."

And that was the message that I got.

And so that led me to become a closet meditator for about 20 years.

Really told very few people.

And then it all changed when I first met the Dalai Lama who basically said to me, you know, "If you can study anxiety "with the tools of modern neuroscience, "you can study compassion.

"There's no fundamental reason why you want to privilege one over the other."

And that was really the inspiration that led me to step out of the closet.

- Jo: Big moment, I'm really grateful to him.

[chuckling] It's really hard to imagine that many years ago, a serious, hardcore neurobiologist resisting all the pressure to give up meditation.

You stuck with it all those years.

And boy, am I glad you did.

- Richard: Well, thank you.

[Jo chuckling] - Sam: We have a question online.

Cece is asking what number of meditations and how long did the full, the didactic and meditation participants, do?

- Jo: It was also a few minutes a day.

Right?

- Richard: Yeah.

So the time for each group was matched about, on average, about five minutes a day, and they'd do this for 28 days, for four weeks consecutively.

- Jo: And one of the things that I find remarkable in Richie's data is you look three months out.

Well, we don't know what they're doing, but they haven't been required to do the app for two months.

And we're still seeing differences in their depression scores and their microbiomes as well.

That's pretty amazing to me, the long-lasting effect that it has.

- Attendee 1: Hi, Jo and Richie.

Really fascinating research, and I'm really interested in these mice transplantation studies and how you can see the effect transferred just by the microbiome.

But I am fascinated in hearing your thoughts on kind of this initiation event.

Like, is it, when people get this depression and these changes in microbiome, are there, like, changes in acquiring the microbes that cause this?

Is it maybe a change in diet?

You had mentioned that there is that, or are some people just inherently harboring some of these microbes that kind of pre, maybe, dispose them to developing some of these conditions?

I'm just curious on your thoughts about that.

- Jo: Yeah, it's a great question.

We know now that most people probably carry most of the microbes.

And what we're doing with any kind of intervention, probably even probiotics, but we don't know for sure, is enhancing the good bacteria if there's a positive effect.

So the bacteria are there.

It's a matter of changing the ratios.

And that's been shown in lots of other conditions.

For example, in obesity, there's no change in who's there, but we see a difference in the ratio of two different phyla of organisms.

And the reason that some of them look like they're not there in the data is just that they're below detection.

But that doesn't mean that they've disappeared entirely.

So if you apply the same pressure to all people, you should see the same kind of effect.

Now, there are a few exceptions of people who don't carry exactly the same cohort, and that might be an especially useful place for probiotics, where we could enhance people's, the whole flora, so that they would flourish more effectively.

We also, we did a study previously with Richie's group looking at stressed police, members of the police forces.

Three police forces in Dane County.

And then they were subjected to meditation training.

And we found in that case that there was no interaction between the microbiome change and the mood change and diet or sleep.

So the microbiome effects we were seeing were clearly due to the meditation and not these, at least those two other lifestyle effects.

- Richard: Well, one of the really, I think, cool opportunities in the future is we've been thinking about ways of enhancing the effects of meditation.

And one of the things that would be really interesting to explore is a hybrid intervention, where we combine probiotics with meditation to see if there are synergistic effects.

And that's something that's never been done before and I think would be extremely interesting.

- Jo: Yeah.

- Attendee 2: So I guess my question is connecting to the past, Barbara Bendlin's research.

Is there research potentially being done with the Wisconsin Alzheimer's Disease Research Center since we truly are, sadly, in an epidemic of dementia, going forward, connecting to what we're talking about now, the research that we're discussing, and meditation for the potential prevention and/or avoidance, that is, of dementia in one's life?

- Richard: Yeah, I'm, maybe both of us have something to say about that.

I'll just say briefly, we're super interested in this question.

We've been doing a little bit of work on this, and we have the aspiration to do more.

One of the fascinating things, and there's a scientist in our center, Melissa Rosenkranz, who has been studying asthma.

And it turns out that while asthma is associated with an inflammatory response in the lung, it also seems to be associated with an inflammatory response in the brain, and that actually causes premature neurodegeneration and cognitive decline.

And this has led to a whole interesting set of questions.

And there are now ways of probing neuroinflammation non-invasively, using certain kinds of brain imaging, and inflammatory responses in the brain may be one of the contributory causes to dementia.

And so the same physical lesion may be associated with very different patterns of inflammatory response.

And the symptoms of dementia, at least in part, reflect the inflammatory response, which is something that we believe can be modulated by the kinds of strategies that we're talking about.

And related to this is there, we've done research with super expert meditators, and we had the opportunity to do a case study of one of these meditators over the course of 12 years.

And he came to our lab many, many times over the course of this 12 years.

So we had serial MRI scans, and we compared him to a database of 1,000 normal people over the same age range.

And while all our brains age, his brain was aging more slowly compared to the 1,000 people in the database.

It was the most extreme data point.

And this is using objective measures of brain aging that you can derive in an automated way from an MRI scan.

So I have absolutely no doubt that the training of well-being can produce changes in the brain that at least decrease the... Let me say it this way, that slow brain aging and may have some positive impact on susceptibility to certain kinds of, to more severe symptoms of neurodegeneration.

- Jo: I have not seen a great probiotic study with Alzheimer's, but there is one with Parkinson's that's fantastic, and it really is very compelling that taking this probiotic slows the progression and sometimes even reverses some of the symptoms of Parkinson's.

So it's possible for Parkinson's.

It should be possible for Alzheimer's.

- Sam: We have a couple more online questions, specifically, Jo, relating to the fact that you mentioned diet recommendations.

A lot of folks are interested about anything that you have to say to that.

And also, if possibly any additional notes on what was monitored diet-wise in the research.

- So, going forward for diet, even though I'm not a physician, I'm not a nutritionist, I feel comfortable saying this because I think it's such a good recommendation, generally.

The evidence is that the more varied and diverse the microbiome, the members of the microbiome are, the healthier people are.

And so every time we look at the microbiome and a disease, it almost always becomes less diverse.

There are fewer kinds of bacteria there in the disease state than in the healthy state.

And what's striking about diversity is that we can generate it, because the diversity of fiber sources that we feed our microbes causes a diversity of microbes.

So there are different ones that can ferment different kinds of fiber.

So cellulose or hemicellulose or pectin, these are all the different kinds of fibers that we eat.

And so diversifying your fruits and vegetables is probably the single most important thing we can do for the gut microbiome.

We don't have anything a whole lot more specific than that.

We can't give you a recipe for a milkshake that will make your microbiome happy.

But I do have a colleague in New York who studies the microbiome, and I visited him once at home, and he pulled out his blender and he said, "You got to try my milkshake."

And he doesn't use real milk, but he uses 60 different plant sources to make this smoothie every day.

And you can imagine the diversity of microbes that can feed on those different plants.

So I think the simplest diet recommendation is diversify, increase fiber.

And I think Federico Rey talked about how hard it is to get enough fiber in the last talk.

More fiber and more different kinds of fiber is probably the single biggest act we can do nutritionally to benefit our microbiomes.

And we don't have a lot of diet data.

It turns out diet is extremely hard to track.

People have used many different kinds of measures of diet, and people, we're just not very good reporters.

We have lousy memories, and we imagine we've eaten things we haven't, and vice versa.

[Richard chuckling] And so, in the future, we are gonna be tracking that in the next study.

But we actually have found a measure that's really easy of just asking people if over the last week they have eaten these different foods.

And it's much easier to remember what you've eaten when you have a list in front of you than it is to just conjure up what you've eaten.

So that has been shown to be a pretty reliable measure, and we're hoping to incorporate that into the next microbiome study.

- Attendee 3: Thank you, that was a great talk.

I was wondering then in terms of SSRIs.

So is then meditation something that we could be looking forward to in terms of treating people with depression, when it comes to prescribing SSRIs, 'cause we know that different people react or respond different to different types of medication?

And would the microbiome, could also inform which prescription would be even better?

Do you have any notes on that?

- Jo: Yeah, those are both great questions.

And I think the evidence from this study and others of Richie's is that meditation is definitely good for depression.

We're planning another study that is a little bit risky, to replace drugs with meditation, because it's on adolescents, and we don't really want to take responsibility for preventing a severely depressed adolescent from getting the drugs that they need.

So that's actually, ethically, a complicated question is can you actually do that replacement?

But the combination is great.

And hopefully, meditation will augment the effect of the SSRIs.

I have another study with Ryan Herringa, who's in the psychiatry department, where we got samples of the microbiome before he put kids, adolescents on antidepressants.

And we can now look back, and the data are literally at the biotech sequencing center right now.

We can now look back and ask, "Okay, now that we know who responded to the SSRI "or whatever drug they're on, "do we have markers in their microbiome that would predict that they would respond?"

And then going forward, we could actually retest that.

So we're hoping to get data on that, but it's a really tough study to do because it means getting people as they're being prescribed the SSRI, or delaying their start of the drug, which is questionable ethically as well.

So we're working on that.

- Richard: That same question we'll be able to address in the study we're doing together now, because we have microbiome samples before participants start meditating.

And we can ask whether the microbiome actually predicts their response to meditation.

So that's a related question that really hasn't been addressed before.

- Jo: Yeah, we call those the responders and the non-responders.

And we want to ask if, at baseline, before they start, can we differentiate their microbiomes?

And so far, the preliminary evidence is yeah, probably.

- Sam: Thank you, everybody, for joining us.

One more final round of applause for Dr.

Richie and Jo.

[audience applauding] Wonderful conversation, thank you again for joining us.

[audience applauding]