Do microbes help or hurt you? (featuring Katrine Whiteson)

Daniel and Kelly talk to Katrine Whiteson (a Whiteson Prize laureate) about the complex relationship between humans and microbes

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Episode Transcript

Speaker 1 (00:05):
Nobody likes getting colonized by microbial invaders, Those little guys
swimming around inside you, messing up your body's normal function,
hijacking yourselves to make more themselves, meanwhile giving you headaches
or sniffles or stomach pains or even worse. No, we
want them out. We take medicine to kill them, or
we wait for our immune system to hunt them down
and root them out, leaving us with pure, unpolluted human bits.

Speaker 2 (00:30):
Right.

Speaker 1 (00:30):
Not really, Actually, the truth about our relationship with microbes
is much more complex. They not only fight on our side.
Sometimes most of the time we can't even tell who
is on which side, or if there are even sides.
Maybe it's more like a big microbial economy than a
black and white battle. Today in the podcast, we're gonna
dig into the life of microbes and the role they

(00:51):
play in keeping us healthy and sick. Do they help us,
do they hurt us? Or is the answer? As always,
it depends a word to today's parents. Today's episode is
getting a little gooey. We can't talk about microbes without
talking about pooh. It's always a conversational risk when talking
to biologists, so keep that in mind if you're playing
this episode with your little ones. I vote let them listen.

(01:13):
There's pooer in knowledge. See what I did there? Either way,
Welcome to Daniel and Kelly's extraordinary microbial universe.

Speaker 3 (01:35):
Hello. I'm kellyleener Smith. I study parasites in space, and
today we are talking about one of my favorite topics
as a biologist, which is to say, microbes and poop.

Speaker 1 (01:46):
Hi. I'm Daniel. I'm a particle physicist, and I have
poop in my freezer.

Speaker 3 (01:50):
Oh oh, that's a little too much, all right? So
what is the most unpleasant microbe related thing that's ever
happened to you?

Speaker 1 (02:00):
You want to hear about every time I had diarrhea?

Speaker 3 (02:03):
Maybe the one worst time is what I was thinking.

Speaker 1 (02:06):
I guess maybe not to hear about that.

Speaker 3 (02:08):
Never mind, I'm backing off. For me, it was an
infection that was a healing and that was unpleasant. We
should go in a different direction. What else should I ask?
Here's my question for you? What is your favorite thing
to consume that increases the diversity of your microbiome however
temporarily well.

Speaker 1 (02:25):
As you'll hear in our conversation with Katrina in a minute,
we are big fans of beans, in the whites and household.
And so we're even members of the Rancho Gordo Bean Club,
which means we have mailed to us every few weeks
a box of heirloom beans, and so we have all
sorts of crazy beans and basically we have beans at
every meal.

Speaker 3 (02:43):
Wow. So you must have like the best bean recipes?
Can you send them to me?

Speaker 1 (02:48):
Absolutely? Yeah, we'll share some with.

Speaker 3 (02:49):
You because I got to say, after this conversation with Katrina,
I am starting to think about how beans can be
incorporated into every one of our dinners.

Speaker 1 (02:56):
At least we put lentils on everything. They're in salad
and everything. They're fantastic. Yeah, we're big fans of beans.
And our son loves beans too, which is a great outcome.

Speaker 3 (03:05):
You didn't mention your daughter. Does she not love beans?

Speaker 1 (03:07):
She's not yet on the bean wagon. Yep.

Speaker 3 (03:10):
You know it's hard to get kids on the bean wagon,
I imagine. Yeah.

Speaker 1 (03:14):
Well, you know, with lots of foods, you can start
with like the easier version, you know, like if you're
gonna start drinking coffee, you put milk and sugar in it.
I'm not quite sure what the easy way is with beans.
Maybe put lots of cheese on top or something.

Speaker 3 (03:27):
At tacos has got to be tacos tacos.

Speaker 1 (03:29):
Yeah, exactly. Anyway, today we are talking about really fun
and really important topics, what's going on inside our bodies
and on our skin, about all those critters that are
living with us or who are part of us.

Speaker 3 (03:42):
And you asked our listeners a question to gauge how
subtly they understand the importance of bacteria in our bodies.
So you ask them, do microbes hurt you or keep
you healthy? And here's what they had to say.

Speaker 4 (03:54):
Microbes in your body are what allow you to function
at all, So yeah, they're helpful, although some kinds of
microbes are bad for you and they will hurt you both.

Speaker 5 (04:07):
There are good microbes and bad microbes.

Speaker 6 (04:10):
Providing the microbes in your body are kept under control
in their number and their type, they can definitely help you.
But if you get introduced microbes or the microbes get
to a critical number, then they can also cause harm.

Speaker 5 (04:25):
Like most questions in biology, the answer is it depends.
For example, your digestive system doesn't work without microbes, but
if you have too many of the wrong ones, then
it doesn't work at all, we.

Speaker 7 (04:39):
Couldn't live with the microbes in their body.

Speaker 8 (04:41):
I'm onto you now with your deliberately vague questions. So
microbes in the body, I think what you wanted me
to say was in the body, but not in the bloodstream. However,
I think the research has changed on that, so I
actually think you do have microbes in the bloodstream now,

(05:03):
but by notche Yeah, they are good for you.

Speaker 2 (05:06):
I read somewhere that our bodies are whole ecosystems, so
I would say that on the whole, the microbes are
beneficial to us. Hope they do both.

Speaker 7 (05:17):
They help you and they can hurt you if they
metestasize turn to cancer.

Speaker 9 (05:21):
Microbes in our body are good and help, but there
might also be bad microbes that you could get that
would make you sick.

Speaker 1 (05:31):
They can help or hurt or neither, or either one,
depending on where it happens to be.

Speaker 10 (05:38):
I think the general rule of thumb is that the
microbes that are in your body are there to help you,
whereas the microbes that are trying to get into your
body from the outside are the ones you gotta worry about.

Speaker 2 (05:49):
I believe the great majority of them are benign and
useful microbes compared to the rare and wanted to intruders.

Speaker 1 (05:59):
Help, absolutely help.

Speaker 7 (06:01):
I can barely distinguish myself from my microbes.

Speaker 9 (06:05):
Finally, a question I can actually answer as a nurse.
Microbes in the body can be harmful or beneficial. It
depends on the type of microbe, the quantity of that microbe,
and the location of that microbe.

Speaker 7 (06:19):
Both because some are bad for your body, like germs,
and some are good for your body like good backter.

Speaker 11 (06:25):
Yet, there are forty trillion microbes in your body compared
to thirty eight trillion human body cells in your body,
and the majority of the microbes are there to make
you feel better.

Speaker 1 (06:41):
And then every once in a while on the balance
is out of whack. They get into stuff they're not
supposed to do and cause us a little bit of damage.
But hey, what areferens for?

Speaker 10 (06:52):
Microbes span the gamut from being critical for functioning to
being lethal.

Speaker 12 (06:58):
We might not exist without micro It's something like ten
times more microbes than human sells in the body. They
help with digestion and glucose metabolism, help absorb nutrients in
the body.

Speaker 7 (07:12):
Classic science answer it depends, Oh, this.

Speaker 9 (07:15):
Is a false dichotomy microbes both hurt and help you.

Speaker 5 (07:20):
I think microbes in our body are the part of
our body.

Speaker 1 (07:24):
These are great answers. Thank you very much to our
list of volunteers, and remember you can join them at
any time. Just write to us two questions at Danielandkelly
dot org and we will hit you up next time. Kelly,
what did you think of these answers?

Speaker 3 (07:37):
I liked I can barely distinguish myself from my microbes.
That made me smile. I wanted to learn more about
the cancer and bacteria link. I don't know too much
about that. Yeah, what about you? What was your favorite answer?

Speaker 1 (07:49):
I like the person who said that they're onto us
with our deliberately vague questions. This whole thing is some
kind of scheme. Yeah. I thought these were great, and
they show that people have, all right, a pretty nuanced
understanding of microbes. They're not just pathogens. They're part of
who we are and how we live and all of
our futures.

Speaker 3 (08:08):
All right, Well, I think it's time for us to
dig in with the interview with our special guest today.

Speaker 1 (08:15):
So it's my pleasure to welcome back to the podcast,
Katrina Whitson. She's the senior editor of the whites and
Science Report quarterly journal, and she's the current holder of
the whites In and Down Fellowship for actual experimental science,
not just computer stuff. WHOA welcome to the pod.

Speaker 7 (08:31):
I don't think you guys understand what a big concession
that was. There have been times at U see Irvine
where there were three whites and labs. There was Daniel Whitson,
who you all know and love, shimone Whiteson, his brother
who is a computer science professor at Oxford but came
into a sabbatical here. And then there was the actual
whites Inn Lab Katrina Whitson, where there's like a physical

(08:52):
lab and there's people in there growing microbes and glasswere
being autoclaimed and stuff like that. It wasn't just like
in the cloud. You know.

Speaker 1 (09:01):
Well went out here today to debate the philosophical question
of whether stuff on the computer is actual answer or not.
That's just me trying to butter you up.

Speaker 3 (09:08):
From the episode. I think we should bring you back
for that debate.

Speaker 7 (09:10):
Though I know that what Daniel does is real science.
I don't mean that. I'm just I'm just enjoying the.

Speaker 2 (09:17):
Joke, you know.

Speaker 1 (09:19):
I'm just glad to get that on the air. Wow,
we have that requestion. So today we've invited you on
the podcast because we're talking about microbes and microbes in
the body and whether they help you when they hurt you,
what their role is? Are they part of us? Are
they our friend? Are their enemy? Are they our front
of me? How does it all work? And this is
your area of expertise that we're very happy to talk

(09:40):
to you about it, But first let's get people acquainted
and make sure everybody is talking about the same thing.
Like when I say microbe, what does that mean to you?

Speaker 7 (09:48):
Well, microbes refer to life forms that are too small
to see with the naked eye, but it can refer
to like lots of different branches of the tree of life.
So microbes can be viral, which we even debate whether
they're alive or not. But they're definitely the most biologically
diverse entity on the planet. So viruses, bacteria, fungi like yeast,

(10:10):
other eukaryotic parasites like nightmarish ones that cause diarrhea. But
most microbes are not pathogens. Even though most of what
you hear about microbes are pathogens, most microbes actually are
living their lives. Their goal is never to cause disease.
They're out for themselves.

Speaker 1 (10:27):
You know, they have goals. You mean, like if you
talk to them, they'd have like hopes and dreams.

Speaker 7 (10:32):
Well, I mean, I think all life forms have a
basic goal of reproduction, whether they're like thinking about it
or not.

Speaker 3 (10:39):
Could you give us a bit of our history on
the thinking about this, Like, did we always think it
was bad to have microbes in our gut? Have we
kind of gone back and forth on thinking they're good
or bad?

Speaker 7 (10:48):
Yeah, I mean definitely. Well, the first time we ever
even saw microbe was when Van Lohenhook ground his own microscopes.
He was a draper in the Netherlands, and he was
grinding his own microscopes in order to look at the
threads at the edge of the curtains he was making.
But then for fun, he just took a piece of
dental plaque, like a glop out of his mouth and

(11:09):
looked at it, and he saw the little microbes jumping around,
and he drew pictures of them. He called them animal tules.
That's the first time we saw microbe. At that point,
I think our thinking was pretty neutral. I mean, it
took us a couple centuries to even realize that like
washing hands was a good idea to prevent disease. So yeah,
it was pretty neutral for a while. But then I'd
say by the twentieth century, once cock postulates and we

(11:32):
understood that microbes caused disease, then I think we were
just expecting every time we turned a corner and discovered
a new microbe that it was causing disease. And you
might have heard of like bubble boy or in the
nineteen fifties when we first developed notobiotic cultivation, we at
that time thought like, wouldn't it be great if we
could all be sterile. We really didn't imagine that the
microbes were doing too much positive with a few exceptions,

(11:55):
like there were people who appreciated probiotics around the year
nineteen hundred, we.

Speaker 1 (12:00):
Go back, I want to understand what is nodobiotics and
who's the bubble boy great.

Speaker 7 (12:05):
Noobiotics refers to cultivating animals in an intentional community of microbes.
It doesn't actually have to mean sterile. It can often
mean like intentionally cultivating say a mouse with like ten
known microbes and then like learning exactly how those microbes
affect immune development. And all other kinds of health outcomes.
So noobiotics are a really important tool in microbiome science.

(12:28):
Where we can intentionally cultivate mice or zebrafish or like
pick your model animal of choice. We can't really do
that with people though, With this exception of bubble Boy,
who was a boy who had severe immune deficiency, and
I mean kind of brilliantly, considering the technology available at
the time, his medical community the doctors around him figured

(12:51):
out how to keep him in essentially sterile conditions, like
in a plastic bubble with oxygen pumped in, so that
he was never exposed to microbes that would quickly kill him.
There's a movie about it too, So that's pretty rare
to have a human growing up with that little microbial exposure.
But at that time, we thought like, oh, the more antibiotics,
the more better. Just like pop them down, it'll probably

(13:13):
help you. There was not really a feeling of loss
that by taking antibiotics you were destroying something.

Speaker 3 (13:19):
And I feel like since then we've gone in the
opposite direction where whenever you're listening to a podcast you
get advertisements about bacteria that are so good for you,
And have we sort of gone in the opposite direction.
Are we finding a happy medium?

Speaker 7 (13:34):
That's a good question. I feel like the ads you
hear are sometimes coming from the eighty billion dollar probiotic industry,
which is not really resting upon too much evidence, to
be honest, and so the kinds of things you hear
in those ads are often not all that close to reality.
So I guess it depends a little bit about which
parts you're hearing about. I think the message that we

(13:55):
shouldn't just pop antibiotics without any concern for the damage
they can cause, I feel like that has gotten much better.
So yeah, I think we have come to appreciate that
taking antibiotics has a consequence that's not only positive. Although
keep in mind that eighty percent of the antibiotics used
in the United States at least are in agriculture, so
our own human consumption can only have so much impact

(14:16):
on avoiding the antibiotic resistance crisis.

Speaker 1 (14:19):
All right, So microbes are these little critters that are
too small to see, which frankly feels to me like
a little fuzzy, like if I have terrible vision, are
there some things that are microbes to me? Like if
I can't see cats to the count's microbes because I
have like very bad eyesight. But as usual, it's biology,
so it's fuzzy, no, I mean.

Speaker 7 (14:36):
It's definitely like you know, if I had a slide,
I could give you some images of the scale bar
and the sizes of viruses and bacteria. Like your average
bacterial cell is about ten times smaller than your average
eukaryotic cell. Eukaryotic cells have a nucleus. Those are the
kind of cells that make up our bodies, and there's
also unicellular versions of them. But I mean, yeah, the

(14:58):
point is just that they're tiny, and they tend to
be unicellular too.

Speaker 1 (15:03):
I mean some dogs are tiny too. Around la fit
people's pursus dogs all.

Speaker 7 (15:09):
Right, those dogs have like four thousand times as many
microbes in their guts, is what I'm saying, though, I.

Speaker 1 (15:16):
Mean toy dogs are pretty small. Anyway. You're the expert
on it, So that's a And so you've walked us
through this history where we learned about microbes. Some of
them cause disease, but now we have a more nuanced take.
So tell us, like, if microbes are part of us,
where on the body do they live? Where can I
find microbes in my body.

Speaker 7 (15:37):
I mean, you can find microbes literally everywhere, whether it's
your body or not, and so that's actually a challenge.
Sometimes I start my talks out with this challenge that,
like a key postulate of microbial ecology is that nothing
is sterile, and then I try to think of maybe
exceptions to that, like places where life really can't be sustained.

(15:57):
But I mean you could just check out and environment
deep sea, ocean, vents, hot springs, you know, the outside
of a spaceship, like.

Speaker 1 (16:07):
What about uranus is urinus sterile?

Speaker 7 (16:11):
Wow, Well that depends a bit on the meeting, but
answer well, I think there are places that have very
very low microbial load and some materials that can't really
sustain microbial life so well, like maybe glass for example.

(16:32):
But on average, you know, on your body, which was
your question, we have really really dense microbial colonization in
our gut. Those are mostly microbes that can't survive with oxygen,
Like they're called anaerobes, so they live without oxygen. Most
of the microbes in your gut are anaerobes, which I
just think is amazing because we obviously live in a
world with oxygen, so it's kind of crazy. How all
these anaerobes colonize our bodies.

Speaker 3 (16:54):
We're reversed bubble boys for the bacteria in our guts.

Speaker 7 (16:57):
Yeah, exactly. Even your teeth have really strict anaerobes growing
on them, so your oral cavity is super super densely
colonized with microbes. Like the number of microbes per density
is about the same in your oral cavity and in
your gut, And like in a soil sample where they're
famous for being teeming with microbes, and in your oral
cavity there's just gradients of microbes that gobble up the

(17:20):
oxygen at the surface, so that shields the ones underneath
so that the anaerobs can survive.

Speaker 1 (17:25):
Why do you say oral cavity instead of mouth?

Speaker 7 (17:28):
Wow? I mean mouth is probably a better choice. I
see what you're saying, But I guess I just got
so used to writing papers about oral microbiomes and oral cavities,
And like in the Human Microbiome Project, there were seventeen
sampling sites in the oral cavity. There's symmetry, Like your
two back top teeth on each side of your mouth
have more similar microbial communities compared to ones closer to

(17:49):
the surface having to do with like nutrient access, and
so I think I'm just thinking about that.

Speaker 3 (17:54):
When I say it, we've gotten a little bit farther
away from my favorite topic. So first I want to
point out that Annuel was the first one to mention
poop and butts in this episode, So I win.

Speaker 1 (18:04):
I win.

Speaker 3 (18:04):
You can't always blame the biologists. But I've been dying
to ask you. So I heard that our bodies have
so many microbes, that we have more microbes in our
body than we do cells. But then I heard that
the balance of power changes immediately following a bowel movement
because there's so many bacteria in our feces. What is

(18:29):
the truth, Katrina, I have to know.

Speaker 7 (18:31):
Wow, Well, that's an awesome question, and it's been a
real topic of debate, and it's funny because it's like
the intro slide to every microbiome talk for about ten
years was all about how there's ten times as many
microbial cells as human cells and an average human body.
But then we redid our back of the envelope calculations,
so now we call it front of the envelope, and

(18:51):
now the ratio is estimated to be more like one
to one, but like both the numerator and the denominator
are like highly influx here. I wouldn't swear the life
of my children on these calculations or anything like that,
because it's.

Speaker 1 (19:04):
Really good too, but.

Speaker 7 (19:07):
Like even just estimating the number of cells in a
human body.

Speaker 1 (19:11):
Wait, sorry, are there science conversations that you have that
I'm not in where you are swearing the life of
our children?

Speaker 7 (19:16):
No, definitely not.

Speaker 1 (19:19):
I mean, I gotta wonder now, Daniel.

Speaker 3 (19:21):
I feel like you're often on the show talking about
dangerous situations you'd put the kids in for the sake
of physics. I don't feel like you need to be
high and mighty about this.

Speaker 1 (19:29):
I'm mostly talking about your kids, Kelly.

Speaker 3 (19:31):
Oh oh wow.

Speaker 7 (19:33):
Interesting.

Speaker 3 (19:34):
I'm sending my kids to their grandparents' house when you
guys come to visit next week.

Speaker 1 (19:40):
All right, Sona, you're telling us there's a lot of uncertainty.
We don't really even know whether there are more human
or microbial cells in our bodies.

Speaker 7 (19:47):
I'd say that balance is closer to roughly even, and
I agree that when you have a bowel movement, the
balance would shift because you would lose a lot of
microbial cells every time, depending how much fiber you eat
and if you have really big bowel movements or not.
But no matter what, despite the number of cells, what
we can always say is that the diversity of metabolisms

(20:10):
in our body is heavily weighted towards the microbes, because
human cells can only pull off like a pretty small
number of metabolisms. Like the number of types of genes
is pretty small in comparison to the number of types
of genes that microbes carry. Each microbe can live in
a totally different niche, Like there's microbes that live with
no oxygen or microbes that can live with a little

(20:32):
bit of oxygen, and they each carry very unique genes
for breaking down all kinds of molecules. So like, our
metabolomic diversity is unquestionably much more coming from our microbes
than from our human cells.

Speaker 1 (20:46):
All Right, So, I feel like we're transitioning from talking
about individual microbes to talking about like communities and microbes.
And you're telling us these live here and those live there.
And you hear the word all the time these days,
the microbiome. Yeah, so microbiome just a description of like
microbial communities.

Speaker 7 (21:01):
Yes, exactly. So a microbiome is a community of the
microbes we just defined in a particular environment. So the
microbiome definition includes what the environment is. So like, the
kind of microbes that live in your gut where there's
not very much oxygen is very different than the kind
of microbes that live at the surface of the ocean,
where photosynthesis is a big deal. So it's about what

(21:24):
type of life is sustained in that environment.

Speaker 1 (21:27):
So if I see like a bunch of ladies in
LA with one hundred tiny little dogs that are so
small that I can't see them, so those are all microbes,
and together they make a little microbiome.

Speaker 7 (21:39):
I mean, I can't really just say yes to that.
And you can't see the dogs. That means they're in
your imagination. So then.

Speaker 1 (21:49):
They're philosophical dogs.

Speaker 7 (21:50):
You need some evidence to support your claims. I thought
you were a scientist.

Speaker 1 (21:55):
Wow, I just do computer stuff.

Speaker 3 (21:57):
Actually, it's good to know that. Next time I'm Daniel
and I have a conversation like this, it's okay to
just say I'm not humoring that.

Speaker 7 (22:07):
Oh no, in theory, I see what you're saying, And like,
only Los Angeles would support one hundred people with microscopically
tiny dogs. So that's kind of special to that environment.

Speaker 1 (22:17):
I see your point, So then I want to connect
it back to something you said earlier. You were talking
about the kinds of microbes that live in different parts
of our bodies. Do we have like one microbiome, like
one community of microbes or are there different communities and
microbes that live like in my oral cavity and on
my gut or on the tip of my nose.

Speaker 7 (22:33):
Yeah, there's really big differences in the types of microbes
that live in your gut versus your oral cavity versus
like the dryer patches of your skin on your elbow
versus the oil ear patches of your skin in another
part of your body, like your armpits, say, and also
super interesting most of our bodies. On the skin, we
have a lot of diversity of bacteria, but on our feet,

(22:54):
which are more moist, we actually have more diversity of fungi.
And this is all in health anyway. If we start
talking about transplants, which I imagine we will, there's fecal transplants,
there's armpit transplants, there's ear microbiome transplants, and so getting
a healthy community of microbes going is really important to
our health. But even defining health, of course is really hard.

Speaker 3 (23:17):
Well, can we try to talk a little bit more then,
about what these microbes are doing for us? So you
mentioned that a bunch of the metabolism that happens in
our body is caused by bacteria, and that sounds like
it could be helpful. So what are some things that
our bacteria do for us?

Speaker 12 (23:31):
Oh?

Speaker 7 (23:32):
What a great question. So I mean, to be honest,
a lot of this is still unknown. So that's what's
so fun about our field. I'd say most of the
things that microbes are doing we don't know what they
are yet. But things that they do, for example, are
they can break down fiber. So when you eat fiber
in your diet, actually human metabolism can't handle that at all,

(23:53):
but the anaerobes living in your gut they're really good
at breaking down fiber. And another example that I love
is the sugars in breast milk. They should actually be
called fibers as well. So in breast and milk, about
fifteen percent of the energy is in the form of
sugars or fibers that human metabolisms just can't access at all,
but the microbes can. And so this is a really

(24:15):
important moment in human history, Like what moment matters more
than when a baby is born. That clearly we wouldn't
just throw fifteen percent of the energy that's in breast
milk down the drain unless it was really sustaining something important.
And that fifteen percent of the energy in the breast
milk is sustaining specific microbes that can break down the

(24:36):
breast milk sugars. And then when a diaraleal pathogen comes
through and tries to take up residents in a baby gut,
it doesn't have access to that secret nutrient source. And
so a big protection mechanism for babies in parts of
the world where diarrheal illness is still a really big
deal is if you're breastfed and you have those microbes
that can break down the breast milk sugars, then the

(24:58):
when salmonilla comes through, it was just kind of like cupping,
and those special microbes like Biffido bacterias that can break
down the breast milk sugars dominate the baby gut. That's
probably how most baby guts were organized while they were
breast fed through human history.

Speaker 1 (25:13):
So let me see if I understand you're telling me
that basically the first step in digestion, like I eat
a bowl of beans, it's not that my human mechanisms
get involved and break the beans down, but like microbes
are on the front line and they start the process
breaking things down because.

Speaker 7 (25:27):
I can't the order of events there is a little different, Like, okay,
so you're eating your beans, they get to your stomach,
the stomach acid starts to break things down. Digestive enzymes
come in from your pancreas and small intestine area. So
actually the first chomp at most nutrients is coming from
earlier steps in your digestive tract. And actually the microbial

(25:49):
load is quite low, Like we do have microbes in
our stomach, but at not very high density, and same
with our small intestine. But by the time you get
to the colon, so you need to eat food that
don't get absorbed quickly earlier in your digestive tract to
give your microbes access to them. So if you just
eat white rice or processed foods, those get absorbed real

(26:10):
quick in your stomach and small intestine. But if you
eat things that take longer, then they get down to
where the most dense community of microbes lives, and then
you can give those microbes a chance to break down
the fibers.

Speaker 1 (26:24):
I'm sure ken of these the questionbody, just want to
ask one quick follow up about the baby thing. You're
telling me that human mothers produce something that babies cannot
digest without microbes in their guts, which means, of course
that we've been doing this for a long long time. Yeah, right,
microbes probably evolved with us. But how do babies get
those microbes? Like, do they get them from the mom

(26:45):
Is it during the birth, is it during gestation?

Speaker 7 (26:48):
It happens after birth, But actually there's probably many opportunities.
When something's really important, it's good to have a lot
of ways for it to happen, and so it's not
just only at birth. It could be at birth, but
I would imagine that in a village or a community
in human histories past, where there were a lot of
young children, that this would be passed between siblings and friends.

(27:12):
I mean, you just need to be in an environment
where that microbe exists. So it doesn't only have to
be at the moment of birth. It could be at
the moment of birth, but it could also be really
at any time in the beginning of life.

Speaker 1 (27:24):
All right, Well, that takes us all the way back
into prehistory and the understanding of microbes. And we're going
to take a break and we're going to come back
and we're going to talk about the present and the
future of microbes.

Speaker 3 (27:51):
And we're back, and okay, Katrina, I have a question
for you that I get asked a lot, and I
would love to know what the answer should be. So
I study parasites that manipulate the behavior of their house
and often people will say, Okay, I've heard that our
brains have nerves that go down to our stomach, and
that bacteria do things like release serotonin and dopamine that

(28:11):
can communicate with our brains. So are our behaviors controlled
by our microbiome? Can our microbiome be like you need
to eat more beans or something? So to what extent
are our microbes influencing our behavior?

Speaker 7 (28:27):
Well, I mean a lot. For sure. There's definitely a
very strong gut brain axis, and we've known that for
a long time. Even independent of the microbes, we know
that a lot of our nervous and immune system is
in our gut, and so ninety percent of the serotonin
in your body is produced in your gut, for example,

(28:48):
and it's with the help of neuroendocrine cells in our guts,
but those cells are being manipulated by the microbes. So
there's a really strong connection between the dense community of
microbes in our guts and all of the different types
of cells lining our guts that are interacting with our
nervous system. So there is a very strong gut brain connection,

(29:12):
no question. And there's so much interesting evidence which is
hard to sort through about how if you improve your
diet you can improve symptoms of depression, or if you
meditate regularly you can improve your inflammatory state and your
microbiome composition.

Speaker 1 (29:29):
Where you're saying, it goes both directions, not just microbes
or influencing how we think. But your brain can like
control the microbe somehow.

Speaker 7 (29:35):
I mean when you say it like that, it sounds fantastical,
but I mean I literally just watched Joe Handlesman give
a talk last week about how people who were meditating
regularly had improvements in their microbiome, and defining an improvement
is a really hard thing to do in our field.
So you know, ask more questions if you want, but yes,
it goes in every direction. Because our microbe composition is

(29:58):
influenced by the environment, and if you do things that
helped to change your stress levels and the types of
inflammatory cells that your body is inhabited by, then that
changes the environment, and it changes which microbes are winning
the battle of survival in your gut at that moment,

(30:18):
and which microbes are there to break down the foods
that you're eating. So, yeah, there's a very tight connection
between our guts and our minds. But we're really at
the beginning of figuring that out. There's a few conditions
that we are starting to have really good evidence, like
for Parkinson's disease, there's symptoms in the gut arising well

(30:39):
before other symptoms like constipation, and that was one of
the clues that helped us try to disentangle how the
microbiome is involved in Parkinson's disease development. I'm so curious
in ten years, like what we're going to understand better.
But there's really cool evidence emerging all the time.

Speaker 1 (30:57):
So you've mentioned several times that the microbe was played
roles in digestion, et cetera. Do we know what like
a good microbiome is, Like, do we understand what your
microbiome should be doing and what its composition should be,
and is that true in the gut or am my
nose or my ear.

Speaker 7 (31:16):
That is still a science question, and I think it's
also maybe a philosophy question. Even just to define health
is really interesting, and our field has had a lot
of interaction with philosophers through the years to try to
define what health is. For example, at the operation nearby
in Testine for the product to VOUST, where they harvest

(31:38):
so called healthy fecal spores from so called healthy donors
in order to treat the diarrheal pathogen c DIFF. They
have to decide who can be a healthy donor and
they screen people and only one percent are considered eligible.

Speaker 1 (31:53):
To be clear, what we're donating here, are bms right?

Speaker 7 (31:56):
Yes, So they get volunteers to come and poop on
site four to six times per week and then they
harvest the spores out of their poop and that is
the product VOUST, which is being used to treat se DIFF.
It's one of two FDA approved microbiome therapies in the
country right now.

Speaker 3 (32:10):
It's got to be hard to schedule, like you can't
just do that on cue. My son seems to be
able to. But he's the only one I've ever met
who can do that.

Speaker 7 (32:17):
Yeah, I think they have like a big line in
the morning. So people who can do that regularly. I
remember asking in one of my classes ones like, who
knows when they're gonna poop every day? Like, is it
like something you know when it's gonna happen, or is.

Speaker 1 (32:29):
It like you're asking people about this in class and
public that like raise their hand to talk about their
poop schedule.

Speaker 7 (32:34):
Well, it was when I had somebody from the company
Voused visiting to speak and she had exactly the question
you just had, Kelly. Anyway, there were some people who
were like, how could you not know when you're gonna poop?
I always know when? And other people who were like,
I would never be able to guess that. That's clearly
like something that's different about each person.

Speaker 2 (32:50):
Huh.

Speaker 7 (32:50):
But you know, one percent of people are not the
only healthy people. And I think that we need to
think about what we mean by health differently. When I'm
writing my ethics view approval documents for the studies that
I do, I have a very expansive definition of what
I think health is, And to me, health is someone
who's out and about living their life, like a student

(33:11):
in my class is definitely considered healthy that otherwise they
couldn't like show up and be a college student if
they have some allergy or some other kind of defined
disease it's been diagnosed. In my mind, that doesn't like
knock them out of the category of being a healthy person.
And so that's a really difficult question to answer. But
your question was do we know what a healthy microbiome is?

(33:31):
And that was actually what the goal of the Human
Microbiome Project was. It started in two thousand and six
and they got three hundred healthy donors in the United
States to give samples, and healthy was defined somewhat more inclusively,
I think than the one percent that were accepted in
that other donation context. And the goal was, like, what's
the core human microbiome? Like, what are microbes that are

(33:54):
shared between everyone? And the fascinating thing was that every
time you added one more to the study, the then
diagram overlap got smaller and smaller until there was nothing left.
So there were no core human microbes. Everybody is different
enough that there just really isn't a core human microbiome,
depending how you define it.

Speaker 1 (34:13):
So you're saying, for example, person A is totally healthy
and living their lives and having great poops and doesn't
have anything in common gut bacteria wise with person B,
who's also healthy and can eat beans and doesn't have
terrible digestive problem.

Speaker 7 (34:28):
Yeah, people are extremely different from each other. If you
only had two people, I bet you would find some overlap.
But by the time you get to about ten people,
you probably don't have much overlap left anymore. And then
really big differences occur when you look around the world,
and so there's really cool patterns of people who live
in less industrialized places, where they eat more plants and

(34:49):
less processed food, their guts tend to be dominated by
plant breakdown microbes that are good at breaking down fiber
and probably have other properties too, Whereas if you look
in the industry world, and this is like so scary
to meet that most people in the industrialized world have
a lot of mucus breakdown bugs in their gut. So
basically we're starving our guts of fiber, and as a result,

(35:12):
the microbes are like turning to us and just like
eating the mucus that's produced by the cells lining our gut.
So there's this bug called Acromancia that's very common in
the industrialized world, and bizarrely, it's even marketed as a
probiotic because it has been associated with positive outcomes. But
it's breaking down the mucus, which is the only thing

(35:33):
between you and sepsis. You have like literally millions of
cells of microbes in your colon and there's one layer
of cells, this epithelial lining of cells lining your gut,
and if that barrier breaks down, the microbes get into
your blood and that's the blood infection that's called sepsis.
That's deadly. And so your mucus lining, that one layer

(35:54):
of cells is a really important part of the barrier
protecting you. And so we're we have a lot of
bugs that are breaking down that mucus. Maybe there's some
kind of feedback there. I mean, these are all science questions. Maybe,
like the bugs breaking down the mucus stimulate its production,
and maybe that's not all bad. But just the fact
that it's so common in the industrialized world and missing

(36:17):
in the parts of the world where people eat more plants,
it kind of makes me want to have the plant
type of microbiome, not the mucus breakdown one.

Speaker 1 (36:24):
So then where can we expect similarities between microbiomes? Like
you and I live in the same house, you mostly
use similar foods, use the same toilets. Do we have
similar microbiomes? Do we expect them to be similar?

Speaker 7 (36:34):
Definitely. That's one of the biggest signatures in every microbiome study,
after the individual, is the household and the family. So
when you collect samples from people who live together, they
have so much in common, and so that's a really
really cool way to do a study. Like my favorite
way to do a study is with household controls, so
you can compare people with the same background, and otherwise

(36:56):
to do longitudinal studies where you take samples from the
same person through an intervention and then use their starting
point samples as the baseline, because if you try to
do it cross sectionally where everyone is so different, it
just doesn't work at all. And back to the household question.
I mean, I really love studies that get into that.
And I have a friend down in San Diego, David Pride,

(37:17):
and he did a study once where he compared married
couples who'd been living together for a long time with
Craigslist roommates who moved in together, and after six weeks
they shared a quarter of the viruses in their gut communities.
So sharing a kitchen and a bathroom is enough to
share a lot, huh.

Speaker 1 (37:35):
The Craigslist connection, Yeah, yep.

Speaker 3 (37:37):
How much do our own individual microbiomes change over time?
So if you looked at a family now or five
years down the road, how consistent would their microbiome be.

Speaker 7 (37:47):
They're quite consistent through time in families and households, but
they're evolving because you know, microbes have high mutation rates.
They don't correct themselves as much as ourselves do. So
in a virus community, for example, there was one grad
student who took samples from himself throughout grad school, which
took a couple of years, and between the beginning and

(38:09):
end of grad school, some of the viruses in their gut.
I'm sure it was anonymous, so maybe I shouldn't say
the name of this dadue. But anyway, some of the
viruses had mutated more than three percent in their genomes,
which is the definition of a new virus. Each of
our guts is kind of like its own little chema
stat where evolution can keep happening, and so through time,

(38:30):
enough mutations arise that it could even be considered a
new species of virus that's emerging. The other thing that
happens is like say you travel and get diarrhea and
really shake things up, or you take antibiotics, you can
kind of like get your community steering to take a
sharp turn after things like that.

Speaker 1 (38:48):
Wait, walk us through what's happening there, Like when you
get diarrhea or you get seedp what's going on there?
Something is coming in and out competing the microbes in
our guts or what's going on?

Speaker 7 (38:58):
Yeah, exactly. So oftentimes a diarrheal pathogen, what will happen
is that they'll come in with some toxin or some
like really big hammer that causes big.

Speaker 1 (39:09):
Changes, meaning that it kills the other microbes.

Speaker 7 (39:12):
Or that it just triggers an enormous immune response, which
brings in a lot of oxidative stress. And I was
just telling you how the microbes in our colon's hate oxygen.
Well inflammation is basically a pile of oxygen. So bringing
in all those inflammatory cells and molecules, that's a tough
condition for a lot of the bugs that live in

(39:34):
our gut. And then you'll have an outgrowth of the
kinds of bugs that can tolerate oxygen. In fact, when
you study the microbiomes of people who have a terrible
gut infection, you don't often find that the bug causing
the infection is the most numerous. This really surprised me. Actually,
I've done a few studies like this with lustratia deficial

(39:54):
infections here at the CI Medical Center, and my naive
expectation was that you I see like, oh, it's ninety
percent seed difts, so they have a sea diff infection.
But that's not what you see at all. You just
see a bunch of bugs that can handle oxygen basically,
and then there's probably a small number of sea diff
cells that are just dumping toxin that's causing all that inflammation.

Speaker 1 (40:15):
That's really mind blowing, I mean, especially if you start
from the point of view of like, diseases are microbes
that come in, pathogens come in and colonize the humans.
Now you're giving us a whole new way to think
about what disease is. Now it's like microbial war where
what's really being damaged are not the human cells, but
like the microbes on our side that were doing their

(40:36):
job for us.

Speaker 7 (40:37):
Yep.

Speaker 1 (40:38):
So it's really we're sort of like a host. We're
just like the battleground for this microbial confrontation.

Speaker 7 (40:43):
Yeah, exactly. I really like the concept of a holo biome,
which is the idea that you know, you are your
own genome and cells, and then you are host to
a community of microbes which comes from the environment that
you live in. So all the microbes in the environment
that you live in, and then some subset of them

(41:04):
colonizes you. And so part of your environment is your diet,
and part of it is like how much time you
spend playing with dirt, so like your exposure to microbes.
Who your roommates are, you know, stuff like that. Like
sometimes people ask me, well, how can I get a
healthy microbiome if I don't have one yet, And like
one piece of advice would be to get a really
healthy roommate who you knew how to help.

Speaker 1 (41:28):
You didn't cause a lot of stress here. People are
gonna blame their diarrhea on their roommates. Now, if you
only did the dishes, then I wouldn't have diarrhea.

Speaker 3 (41:37):
Or maybe you cleaned the bathroom too much. I needed
your good microbes submand at them for that. So I've
got a question about how we even quantify microbiome. So bacteria,
you know, they can undergo conjugation, so they swap genetic
material with each other. In just the course of a
couple of years, viruses are becoming new species because they're
mutating so much. How do you define a species when

(41:59):
things are changing so quickly, and how do you compare
between individuals when there's all this variability.

Speaker 7 (42:05):
Yeah, what a great question. And like I've been in
this field long enough that I've watched the pendulum swing
back and forth on how we make those definitions. Sometimes
it's driven a little bit by technology, but you know,
basically there have been people thinking about microbial communities for
more than a century. So it goes back to there
was a Ukrainian microbial ecologist who was studying pond scum

(42:29):
in Switzerland and he made these columns called Winnegradsky columns,
which had you know, just what I was talking about
with the oxygen gradients, where you'd have oxygen loving bugs
at the top and then their waste products become the
treasure of the next layer of microbes which need less
oxygen and have different strategies for metabolism. So those layers

(42:49):
of microbes, you could even consider them to be the
unit of selection that matters, and so it could be
defined functionally. Almost since the mid twentieth century started having
molecular techniques for probing all of the microbes in a community,
and this all started with environmental microbiologists. All the human
clinical microbiology people were too busy isolating one pathogen at

(43:11):
a time and throwing anything that they didn't define as
a pathogen down the drain as like unrelevant normal flora
or something like that. So the environmental microbiologists got really
good at these really cool molecular techniques, starting with less resolution,
so they had to define a species based on the
information they could get. So we started like digesting common

(43:32):
genes like ribosomal genes, and using restriction enzymes that we
got out of hot springs and putting them on gels,
and then like if the bands on the gel looked different,
then that would be defined as a different species. So
probably we're talking like a few percent difference in genome
because we were only looking at one gene. Even if

(43:53):
that one gene is exactly the same, there could still
be millions of years of evolution separating those two organisms.
Then we got much better. Now we can sequence everything.
And so when I first started in this field around
two thousand and eight or so, we defined a bacterial
species as being three percent different from the next in

(44:13):
this one ribosomal gene. And that was how we defined
a species. Since then, as our techniques have gotten better,
we've leaned towards using even tighter definitions. So we could,
you know, look at organisms that are almost identical and
only have one nuclear hide difference, and then we would
start to define that as the taxonomic unit that mattered.

Speaker 1 (44:36):
Because these guys reproduce asexually.

Speaker 7 (44:38):
Right, yeah, they reproduce asexually, but they have pretty high
mutation rates. They don't like correct all their mistakes. So
you know, for a virus, every progeny is immutant basically,
I mean, think about that for flu or covid, Like
I think there were actually really great visualizations about that
since the pandemic that helped that become obvious to everybody.

(45:00):
Which is so interesting, Right, if every time a virus
makes a copy, it's a new mutant. Some of those
just fall flat, But that's not the strategy. The strategy is,
like most of them do okay, some of them do amazing.

Speaker 1 (45:12):
Well, hey, look, I'm sure those virus parents love all
their little mutants.

Speaker 3 (45:17):
All right, So let's take a break and think about
the mutants in our life that we love, and when
we come back, we'll talk more about the microbiome.

Speaker 1 (45:43):
All right. So we're back, and we're talking to Professor
Katrino Whitson of the Whites and Research Institute about the
microbes in our body, how they influence our world and
shape our lives. And we're talking about the links between
microbiome and health. And in a minute, I want to
ask you about what we can do to packed our microbiome.
But you sort of laid out this picture that like

(46:03):
these things are in our guts. We don't really understand
why they're so different from person to person. We can't
even really define health. We don't understand necessarily what microbiome
you need to have healthy function. But we know that
there's a connection between microbiome and health, right, And I've
heard about people talk about connections between like the microbiome
and like Alzheimer's or microbiome and autism and microbiome and

(46:25):
all sorts of things in our lives. How much do
we know about the impact of the microbiome on these.

Speaker 3 (46:30):
Conditions, Can I super fast interject. I love that Katrina
is president of the Whites and Institute, but I do
feel like we've never actually mentioned that Katrina is also
a professor at UC Irvine and has her own lab.
Have we given her actual credentials at some point?

Speaker 1 (46:46):
She does have a secondary affiliation that you see Irvine.

Speaker 3 (46:49):
Okay, all right, so she is incredible in lots of ways.
But okay, all right, sorry, go ahead with the question.

Speaker 7 (46:55):
That's nice of you. Well, I mean, yes, we have
observation evidence associating microbiomes with health on a lot of
different fronts, and I mean just it's hard to even
know where to start. But one place I could start
is that when I started my lab at EC Irvine
in twenty fourteen, right when microbiome was becoming big in
the literature and everybody was excited about it, I had

(47:17):
one hundred labs contact me wanting to collaborate. In that
first year, I think I had one grad student just
beginning to join my lab. We obviously couldn't do one
hundred collaborations, so I ended up joining forces with an
ecologist here, Jennifer Martini, and we started a Microbiomes center,
and in the last ten years I have gotten to
study easily one hundred different types of microbiomes. Like name

(47:39):
a type of body example you could think of, I've
probably got some in our lab freezer, and I've probably
studied it's microbiome. And that goes for like lots of
different kinds of creatures, including sharks that eat seaweed from
Donovan German's lab, for example. So we have been going
around and like watching what the microbiomes look like and
taking notes and associating that way health. So a lot

(48:01):
of the information we have is observational. So we still
have in the future a need to do more interventional
studies where we ask how does the microbiome change when
you manipulate it in a certain way. You know, now
we kind of know that microbiomes are associated with obesity
and cancer and so forth, But then what do we
do about it? That's kind of like the next ten

(48:21):
years of challenge. And there's a few glimmers of really
really exciting outcomes that make me think it's going to
be possible. So, like, for example, cancer treatment is an
area that I think has a lot of room for
big improvement where my colleagues at m D Anderson gen Wargo,
for example, have done studies showing that when melanoma patients

(48:43):
are getting immunotherapy, which usually only succeeds about thirty percent
of the time, and the thirty percent of people who
have a successful immune therapy tend to have a certain
kind of microbiome. Well, it turns out if you do
a fecal transplant from someone who's immunotherapy succeeded into someone
who's immunotherapy failed, you increase their chances of a good outcome.

(49:04):
Or if you ask how much fiber people ate, people
who ate more than twenty grams of fiber per day
have double the progress free survival when they're doing immunotherapy.
And now they're even doing intervention studies where they're getting
people on immunotherapy to eat fiber and they're watching to
see if that increases their healthy outcomes. And that's not
published yet, but I'm very optimistic. So those are the

(49:27):
kinds of things I could see happening in the future.
We even know that vaccine efficacy depends on fiber intake,
so like if you want to have a good response
to a vaccine, eating well and Having enough plant fiber
to support your gut microbes and keep your immune system
going will actually make you have a more robust response
to a vaccine.

Speaker 1 (49:45):
See. I knew tacos are good for you. I always
knew that tacos.

Speaker 3 (49:49):
Exactly what are you putting in your tacos? Why are
your tacos high fiber? Oh? Oh, I see not all
tacos have beans in them, Daniel.

Speaker 1 (49:57):
Real tacos. Are you having like weird virgin the tacos
with beans?

Speaker 3 (50:01):
I guess?

Speaker 7 (50:01):
So, yeah, I guess even Texans put beans in their chili.

Speaker 1 (50:06):
Yeah, no, exactly no, No, Texans have no beans in
their chili. That's very important contrining.

Speaker 7 (50:11):
Okay, well, all.

Speaker 1 (50:13):
Right, So you've mentioned a few ways that we can
impact our microbiome. Let's dig into those in detail. So
you've talked a couple of times about fecal transplants, and
people are probably wondering, like, what are you talking about here?
When I think about transplant, I think about taking a
kidney out of one person's body and putting it in
somebody else's body. Now I'm trying to think about what
a fecal transplant means. Like, walk us through this what's
going on here? How does this work at all? What

(50:35):
do we know about it?

Speaker 7 (50:36):
Okay, well, fecal transplants refer to taking a healthy microbiome
from one person and trying to give it to another person.
We have been doing this since ancient times, so more
than a thousand years ago in China, people were using
what they call golden soup to treat diarrhea. And actually,

(50:57):
since I teach about this in my big classes, and
I've heard so many good stories from my students who
bring up, Oh, yeah, my family's from the South and
we used to do cow Patty's tea to treat diarrhea.

Speaker 1 (51:09):
What really, Yeah, Southern hospitality there you go.

Speaker 3 (51:12):
Yeah, you guys have a lot to look forward to
when you come to visit.

Speaker 7 (51:17):
I mean, this is something you would only do when
you're in dire streets, right, But if you've been having
diarrhea and you weigh sixty five pounds and you can't walk,
you might be up for trying something bizarre to survive,
you know. And so actually, a modern time story comes
from the Mayo Clinic in Minnesota, where a woman who
had a sea diff infection. Sea diff is typically caused

(51:37):
by taking antibiotics and decimating your healthy microbiome, which makes
it easy for sea diff which forms spores in your gut,
to rear its head and make toxins and cause diarrhea,
and it can get really recurrent and difficult to treat.
And the standard of care, ironically is more antibiotics, which
caused the problem in the first place. So a woman
at the University of Minnesota at the Mayo, her doctor

(52:01):
had this, you know, kind of crazy idea like let's
take a fecal sample from her husband and transplant it
into her and see if we can help this situation
get better, And her symptoms improved. Within a day. She
went from having had diarrhea every fifteen minutes and she
was in a wheelchair and was like unlikely to survive
to the next day her diarrhea was resolved.

Speaker 3 (52:23):
It's incredible.

Speaker 1 (52:24):
I think you're skipping over some of the crucial steps involved,
Like when you talk about this fecal transplant, are we
talking about the northern route the southern route, Like how
do you get it from him into her?

Speaker 7 (52:33):
Yes, good question. You've heard me say my northern and
southern route joke. Well, I mean your digestive tract is
a tube, so you have a couple of entry points.

Speaker 1 (52:44):
She's so polite for me.

Speaker 7 (52:47):
And so to do a fecal transplant, you can take
a healthy sample, put it in the blender and then
get it into a nasal gastric tube down into your
stomach from the northern route, or you can do it
more like an enema into the bottom part of your
digestive tract. You can also make capsules, and you would

(53:09):
need to swallow about twenty or thirty glisterin capsules that
have poop in them to have an impact, which reminds
me of a favorite story. Stanley Falco at Stanford in
the nineteen fifties was a hospital technician as a young man,
he's now like he was one of the fathers of
the hygiene hypothesis, But as a young man he was
helping a surgeon who had this idea that they could

(53:31):
hide healthy fecal samples from before a patient had surgery
in their ice cream and they could eat that post
operatively as they were waking up, because a lot of
people were getting diarrhea from the antibiotics they were getting
in the surgical ward, and without telling them, they had
them eat ice cream with these fecal glisterin caps in there,
and it was working great, like nobody was getting diarrhea.

(53:54):
But when the director of the hospital found out, he
fired them.

Speaker 1 (53:58):
Yeah yeah, no more Brownie Chunk ice cream.

Speaker 7 (54:03):
But they've all recovered and that thinking got them really far.
So that was actually very ahead of their time to
be doing that in the nineteen fifties. But then it
was around twenty ten or so that this story in
Minnesota I told you about emerged, and then since then
it's become like really a sought after treatment for sea
diff but very hard to regulate. It's kind of similar

(54:24):
to blood donation, like we haven't figured out how to
make synthetic blood and it's still a quest, and similarly
for fecal material, it's a quest to figure out like
what is even in there, which parts of it are
needed to make a fecal transplant successful.

Speaker 1 (54:37):
So what's happening is that, like my microbiome is devastated,
which is why I have Diarrhea'm getting somebody else's community
that comes in and then grows into some healthy community.
That's the idea.

Speaker 7 (54:47):
Well, that might have been initial thoughts on what the
idea was, but interestingly in the last fifteen years, we've
tried dissecting the poop into its various components, and so
fascinatingly we've discovered that many of the components are enough
to work as a fecal transplant. So you can filter
the poop and only give the liquid supernatan, which has

(55:07):
molecules and maybe viruses, but certainly not bacterial cells, and
that's enough to cause a successful so called fecal transplant.
We call it a filtered fecal transplant, and that still works.
Or you can just isolate the spores out those are
cells for sure, and give that as a treatment. That's
the FDA approved treatment for the product v OUST, or

(55:30):
you can take a whole fecal community. There's a Swedish
poop from the nineteen nineties that has been cultivated anaerobically
ever since then.

Speaker 6 (55:39):
Poop.

Speaker 7 (55:40):
Yes, and my students are like, hey, that poop is
older than me.

Speaker 1 (55:46):
Whenever I use the bath though, I never imagine it's
going to go down in history, but this one really did.

Speaker 7 (55:50):
Yeah, this one poop has saved like probably thousands of lives.
This one poop has been cultivated anaerobically for many years,
and so presumably none of the initial molecules from that
poop are present, but just the progeny of all those
generations of microbial growth, and that has been enough to
cure seedff in many, many different people. So, to be honest,

(56:13):
it's still a science question, like what you actually need
to make a fecal transplant work. There also have been
famous failures. There were phase three clinical trials of cocktails
of microbes that people put together in the pharmaceutical industry
thinking that that would work, and it didn't. So there's
a geni sequax about the poop that just works perfect.

Speaker 3 (56:34):
So you mentioned that when you've got the liquid supernatan
without any of the bacteria in it, but you've got
their metabolic excretions plus viruses, it works fine.

Speaker 7 (56:44):
Yeah.

Speaker 3 (56:45):
Does that suggest it's the viruses that actually matter?

Speaker 7 (56:48):
What a cool question. I love that question. I don't
know the answer, but it has been shown in like
a number of different ways. There was a group in
Germany and Kiel that showed this with the viruses with
the filtered fecal filtrate. And then there's a group at
the University of Copenhagen who have done really extensive studies
in this really cool model of baby piglets, and their

(57:08):
goal is to be able to help preterm infants in
the NICKEU. And it's such a good idea because it
would be very dangerous to give live microbes to pre
term babies whose guts are in really bad shape. But
if you could do it with the viruses, you might
be able to create an environment that helps the gut
microbiome develop successfully. And like babies in the nick you

(57:29):
have really bad outcomes with their guts, like a third
become septic, a third get necrotizing enterocolitis, and a third
have what they call healthy outcomes, but I mean they're
really in dire straits. And so I love what the
group at the University of Copenhagen is doing because they're
starting in a model of baby piglets, which is pretty
similar to a human model, and I am optimistic that

(57:49):
it won't take too long before they'll feel like it's
safe to try it in babies because the room for
improvement there is just enormous. So that to me is
like a really really cool way that we could improve health.

Speaker 1 (58:01):
So if you get a transplant from somebody else they
have a different microbiome, it's no guarantee that it's definitely
going to work for you? Is the ideal transplant a
donation from yourself, Like, if you're out there having good
poops every day, should people put some of that in
the freezer for the day when they have surgery or diarrhea.

Speaker 7 (58:18):
I really like that idea. It's certainly been a topic
of conversation in our household.

Speaker 1 (58:23):
Don't dig around in our freezer unless you want some surprises.

Speaker 13 (58:26):
By the way, well, not your favorite part of our freezer,
I know, but I appreciate your open mindedness. And by
the way, when my students have to put vehicle samples
in the freezer for our studies, we joke about like
the right way to do that, and like, if your
roommates don't like the idea, just empty out a box
of strawberry popsicles or like chicken nuggets and you could

(58:46):
just hide your samples in there. And if they're trying
to steal a popsicle, I mean, that's on them.

Speaker 1 (58:52):
Oh they're going to get a popsicle. It's not going
to be strawberry exactly.

Speaker 3 (58:56):
After this conversation, I'm never going to look at popsicles
again say yeah.

Speaker 7 (59:03):
Yeah, So the question was could we do like auto
like self fecal transplants and have that work. And that
has been studied in a lot of different contexts also,
for like recovery from antibiotics. If you really know that
you're healthy, Like maybe everybody should be banking their own
sample at some point in their life when they just
were digesting really well and they were eighteen and had

(59:24):
like been eating really well for the summer or something,
save a moment of that glorious part of your health
in the freezer so you could restore yourself to it.
I like that idea. I've proposed this for different kinds
of context. Like one time I wrote a proposal about
helping people who are going to have to have radiotherapy
for cancer. And often people get essentially diarrhea and other

(59:46):
really rough consequences of the radiation treatment. So the idea
was to restore their health to what they were before
the treatment. But somebody who has cancer might have cancer
promoting properties in their own fecal microbiomes, so you could
certainly bring them back to getting cancer again. I mean
this has been studied extensively, Like this kind of approach

(01:00:07):
has been used. There was a big study in New
York City of people who were getting bone marrow transplants
for blood cancers, where they did transplants from people's before
fecal sample in order to try to help them avoid
getting I mean, people get terrible infections after getting cancer treatment.
So this is an area again kind of like the

(01:00:27):
preacher and babies. There's like a ton of room for
improvement there. But the concern is that you would cause
cancer again, so maybe a healthy donor is safer. And
then I hear your question, well, what if the healthy
donor is really different than you. Well, another thing that
happens is it's rare that we follow up our studies
long enough to really see what happens. But there was
one study of autistic children where they did fecal transplants

(01:00:49):
from a stranger, like a healthy donor, not a family member.
But then they followed up for two years both the
kids with autism and a healthy sibling in the same household.
And I loved that they did this for two years.
This is Rosy Krasmo like Brown at Arizona, and they
found that at first the autistic children who received the

(01:01:11):
fecal transplant from a stranger donor their guts were more
similar to the healthy donor, but after two years their
gut microbiomes resembled their siblings more, but they did have
higher diversity. So it's almost like the fecal transplant kick
started the capacity to carry a higher microbial diversity, But
then all those strains got replaced by strains that were

(01:01:35):
available in the household. So the household influence is really important,
and it makes me wonder like when people get married,
there's going to be a battle of the microbiotas and
somebody's going to win, and that hasn't really been studied
that much.

Speaker 1 (01:01:48):
You know, killed diarrhea do us part? Can we talk
about the probiotic industry you mentioned earlier. It's eighty billion
dollars and I feel like I see pills and powders
and yogurts promoting probiotic this and probiotic that. What's in
those And what's your take on whether they're likely to
do anything?

Speaker 7 (01:02:08):
Well, that's a really big question. It is a really
big industry. I was even just comparing the size of
the probiotic industry in the antibiotic industry, and I think
the probiotic industry might even be a bigger money maker
than antibiotics, but it's close. But I mean that's amazing
to me. Eighty billion dollars, like that's close to the
GDP of many nations. And so whether it could work

(01:02:30):
is one question. And yes, the idea of a probiotic
makes sense. I mean, if you could get the right
bug to the right place at the right time, that's
a great idea. It could definitely work. When we say probiotic,
that includes fermented foods like yogurt and kombucha and kiefer
and miso, and those we actually can see really kickstart

(01:02:51):
diversity in our guts. Not necessarily because the bacteria in
those products are colonizing our gut, but they can kickstart
diversity in a good way. Most people when they take
a probiotic, and many packages claim that it's gonna directly
increase your microbiome diversity. I think a lot of people
when they eat a probiotic, imagine that now that bug

(01:03:12):
is happily living in their gut and they just like
got their community a little happier now. Most probiotics actually
don't do that. Most are transient. So if you are
taking those pills and then you measure people for a week,
you'll see a wash out period and after a week
or so it'll be gone, which is probably not what
people imagine. You also might not want the probiotic to stick,

(01:03:33):
so I always remember the story of a startup in
San Francisco where they evolved probiotics that were good at
binding to mucus, with the idea that they could persist
in the gut. But they forgot about gum mucus and
everybody got cavities in their little study.

Speaker 3 (01:03:49):
I'm not laugh is so complicated, I know.

Speaker 7 (01:03:55):
So on average probiotic packages, you know, they don't have
to have evident for the claims they make on the packages,
so they can say some pretty fantastical things. And actually,
in my Microbiomes class this quarter, we had a probiotic
sus score, like a suspicion score activity where everybody had
to go find a probiotic with crazy claims on the

(01:04:16):
package and then try to investigate the claims and like
what evidence there was for them, and there was not
usually a whole lot of evidence, And the students had
amazing comments afterwards that were like, man, if I saw
a celebrity claiming that a probiotic worked, I just would
believe it. It never occurred to me to like investigate the evidence.
And I'm like, you guys are science students. I'm glad
if you're learning that.

Speaker 3 (01:04:36):
Yeah, it's important.

Speaker 7 (01:04:38):
Yeah. So you know, just off the top of my head,
you know, there's probiotics out there that are named like
happy hoo ha, and they claim to improve your imaginal
micro or like you know, anyway, there's some pretty funny ones.
But there are some probiotics that are well investigated and
people are doing studies with them, and so sometimes they're

(01:05:00):
not sharing the evidence in order to protect their ip.
So it's complicated. But the way the industry is regulated
is just that the probiotics have to be generally regarded
as safe or grass, which is not a very high standard.
I mean, it's a high standard in the sense that
like this thing's not going to kill you, that's.

Speaker 3 (01:05:17):
Good, might give you cavities, might give.

Speaker 7 (01:05:20):
You cavities, or might just do absolutely nothing. And I
mean the supplement industry, even beyond probiotics, is an enormous
industry and there's very few claims and it's pretty hard
to know. I mean, even for you know ourselves, like
Daniel and I we have a son who's an athlete,
and he's always, you know, really willing to do what
it takes to be healthy. And so we've had a

(01:05:40):
lot of conversations about what we understand about what's in
a supplement versus what we understand about what's in a food.
And you know, with the tools we have in our
own households, we can't really assess the safety of food
or supplements. That's why we need infrastructure and institutions that
help us understand that. But a lot of the things
that we can buy in packages might have stuff that's

(01:06:03):
dangerous in them, and we have to be really careful.
So my general instinct is to lean towards food, and
you know the advice to generally not eat things that
your grandparents wouldn't recognize as food, or maybe it has
to be our great grandparents now, because a lot of
the processed foods that are available to us these days,

(01:06:23):
with tons of ingredients we can't even pronounce, it could
be really damaging our health. It's not like I have
really great evidence for every single one, but I think
that leaning towards eating things that you can recognize tends
to work the best for the evidence that we have
right now.

Speaker 1 (01:06:40):
And earlier on you mentioned fiber and beans. Why is
fiber something good to eat? I mean, if you're not
going to do a poop transplant and you're not buying
happy hooha or whatever, if you're just going to try
to do this through like healthy eating and food, tell
us why fiber is important.

Speaker 7 (01:06:54):
Definitely. So, fiber is the part of carbohydrates that doesn't
get digested very quickly. It's longer chains of carbohydrates that
your human enzymes can't even access. So the way to
figure this out is if you look at a nutrition label,
it'll list the total carbs and then it'll list the
subset of the carbs that are fiber. So for a
piece of white bread, it might be like nineteen grams

(01:07:15):
of carbs one gram of fiber. Wheat bread might be
nineteen grams of carbs five grams of fiber. Okay, cool.
So now we're talking like you know, nearly a quarter
of the carbs in that piece of bread is fiber.
It's going to be slower to hit your blood sugar levels.
It's going to persist in your digestive track down to
your colon where all the microbes live and give them

(01:07:35):
some food. So that's pretty good. Now let's talk about
beans and lentils. Half of the carbs in beans and
lentils are in the form of fiber. So if you
eat a cup of black beans or old navy beans
or lentils in a day, you'll get probably ten or
twenty grams of fiber out of the thirty or forty
grams of carbs. That's half of your fiber needs for

(01:07:55):
the day. So the daily recommended allowance of fiber in
the US is twenty five to three five grams per day,
and we're usually getting half of that. Most Americans are
getting ten to fifteen grams per day, So we all
need to think about how to fill our fiber gap.
You always hear about how we're not eating enough protein.
I mean, to be honest, we're probably eating money of
protein in the United States, but we really are not
eating enough fiber. If you eat fiber, you are fueling

(01:08:18):
the microbes in your colon. And then if you do
experience some kind of stress, whether it's antibiotics or diarrhea
or just like literally stress that causes inflammation and oxygen
descending upon you and making it harder for those bugs
to thrive in your colon. When you have fiber in there,
you've given the bugs a place to hide out, so
you can weather the storms of any kind of other

(01:08:40):
fluctuations in your life better and keep the microbes happier.
So like, if you did know you had to take antibiotics,
I would definitely really recommend making sure you're eating enough
fiber and fermented foods actually are another really good contributor.

Speaker 1 (01:08:54):
All right. So that's scientific evidence that chili should have
beans in it. Settled that age old question.

Speaker 7 (01:09:01):
I mean, I don't think there's anyone who would disagree
that if you wanted to protect your microbiome, having beans
in your chili would be a good idea.

Speaker 3 (01:09:10):
All right, everybody, So tonight, grab your beans and your
bino and hopefully Katrina Whitson will be back on the
show and not too long. Thanks for spending some time
with us today.

Speaker 7 (01:09:19):
Awesome. Thank you.

Speaker 3 (01:09:27):
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