Ami Bhatt: Lessons from the microbial world living within us


(soft piano tones) Today, on The Future of Everything, the future of the microbiome. Now, the microbiome has
gotten a lot of attention in the last few years. Now, what is a microbiome? I guess we will learn more, but for the purposes of this discussion, it’s the full set of microbial organisms, chiefly bacteria, but maybe others, that live in different
niches within our body. Our mouth, nasal cavity, skin folds, everywhere that has contact
with the outside world. The gut microbiome is
one of those microbiomes and it’s the community of bacteria living in our digestive system, not necessarily related to disease, but as a normal part of our physiology. We have long known that
there is a lot of bacteria in our digestive tract
and we know, for example, that they help us digest our food. That’s what we were
taught in medical school many decades ago when I
was in medical school. We also know that when we treat
infections with antibiotics, it can alter these species
because these species are sitting in your gut and they also can be very
susceptible to antibiotics so when I treat a patient
for urinary tract infection or for pneumonia, not only
am I killing the bacteria, hopefully, that’s causing the infection, but I’m probably altering the
microbiome of that patient in ways that might lead to some symptoms. They might have some digestive issues that are associated with that antibiotic. Now, it’s become clear that the bacteria living in our gut have much
more complicated relationship with our health and with our disease. They seem to be involved
in our immune system. They seem to be changing sometimes in both acute and chronic disease. The idea has even emerged that
there’s a healthy microbiome, the set of bacteria that
you would love to have and host in your bowel and
that there might be treatments for some diseases that involve
changing the microbiome to get it to be more healthy, so to speak. This has gotten probably
the most publicity in the idea of fecal transplants. Yes, if you’re not familiar
with that, you heard correctly. This is the idea where poop, forgive the terminology,
the technical terminology, poop from healthy people is introduced into the digestive tract
of people with disease in order to help them
normalize their microbiome to hopefully get it back
into a healthy state. So this is getting serious. Ami Bhatt is a Professor
of Medicine and Genetics at Stanford University. She has a medical specialty of hematology and studies the human
microbiome, mostly in the gut, and has developed new ways
to measure the presence of bacteria in the human body and ways to interpret these
for health and disease. Ami, you specialize in hematology, the study of blood and blood diseases. How does a hematologist get interested in bacteria that live in the gut? So, thanks a lot for having me, Russ. It’s a pleasure to be here. I actually first became interested in the bacteria viruses and fungi that live in and on us, as I think many young people did which was by watching a TV show. I remember being about, I don’t know, nine or 10 years old, and I was left at home for the first time, for like ten minutes by
myself or something like that, and so I turned on the TV. My younger brother and I were
watching a television show about germs and, they showed these
horrifying microscopic images of all of the bacteria that are
squirming around everywhere. And I thought, “Wow, this is
fantastic and also very gross “and we should really
learn more about this.” If you fast forward many years later, part of the reason I became interested as a hematologist and oncologist
in viruses and bacteria was because I learned that viruses can cause cancers in some cases. And as you well know, there
are viruses that cause well-known cancers like liver cancer. Liver cancer is caused, in some cases, by a hepatitis virus. We know that the human papilloma virus causes cervical cancer and other cancers. And I thought, “Wow, there are all of these
relatively simple organisms. “They don’t have many genes.” You know, a virus can’t
even live by itself. It requires a human cell in these cases in order to replicate. It’s amazing that such simple organisms can alter the biology of such
complex organisms like us. And so that was how I
ended up getting interested in bacteria viruses and
fungi that live in and on us. Of course, first I learned
about them as kind of bad guys but there are trillions of microorganisms that live in and on us and most of them are
probably not bad guys. Many of them are probably
actually quite helpful and so I’ve taken a more holistic view of what bugs mean to us. So tell me, what are we finding when we look at the microbiome? How many of these are old friends
that we’ve known for years and how many surprises are
there where we’re saying, “Wow, we had no idea that
this bacteria species “was living in us.” And then how do we figure out what they’re doing, good or bad? Yeah, so this is an
incredibly complex question in part because we don’t even
know most of the microbes that live within us. Despite the fact that now, there have been tens of
thousands of papers published on the gut microbiome
of humans, for example, we know relatively little
about who these organisms are. The classical ways of
studying microorganisms was by taking them, culturing them, looking at them under the microscope. Right, give them a little
sugar and they’ll grow. Exactly. Describing them
based on what they grow on, so what they like to eat,
what color they stain, what shape they are. But now what we’re
understanding is organisms that look really similar
under the microscope, and have very similar growth
characteristics, for example, can have totally different genomes which means that they can probably do totally different things. So one of the things that
we’re learning in the field is that we know relatively little about the organisms even
within our own guts. And so a lot of effort has been put into trying to better
enumerate who’s there and what they’re doing. And I also know that these bacteria often, you can’t just grow
them on sugar and salt, they actually need each other to live so it’s like a very highly
interlinked environment. Is this idea of a healthy microbiome, is that an oversimplification
or is it in fact true that you could look at a
sample of somebody’s poop and say, “That looks pretty good,” versus, “Oh, we have a problem here.” You know, I think in general
we’re coming to a consensus that for the gut microbiome, at least based on the individuals who’ve been studied to date, having a more diverse community is better. And so having a larger
variety of different types of organisms is probably
better than the alternative, which is having a handful of organisms that are present at a high abundance. But in general, what we think we know now is that there isn’t just
one healthy microbiome. There isn’t that golden poop out there that we should fecal
transplant into everyone and then we’ll all look like a Kardashian and live for 250 years. I know a young man in Boston whose name will not be mentioned who’s actually made several thousand dollars donating his poop to research and to microbiome stuff for the last couple of
years so he’s in the money. Yeah, oh yeah. It’s a great way to, you know, turn poop into cold, hard cash. Poop into cash. (laughs) Okay so that was a very distracting idea. So there are many healthy microbiomes. And how can a patient or
a person who’s listening, how can they figure out what the state of their microbiome is? You know, it’s interesting. I think if I talk to most
laypeople or my patients or family members who aren’t in medicine and I ask them, “How’s your gut health?” Most people can actually tell you. Most people have a very good sense of how their gut is functioning based on their daily bowel
movement or bowel movements, how they feel, do they feel bloated, etc. And so I would say most people who don’t have gastrointestinal symptoms, I’m talking about diarrhea, constipation, nausea, vomiting, bloating, those are people who probably have fairly healthy gut microbiomes. So that’s good news ’cause that means you can use your normal life experience to kind of self-diagnose
if there’s a problem and if things are going well both literally and figuratively, then we’re okay and then
there’s no need to worry. So what are the impacts Well, this is The Future of Everything. I’m Russ Altman, I’m
speaking with Ami Bhatt about microbiomes and
healthy and diseased ones. What about when you take antibiotics? This is a huge insult to the system. Do we know what happens
to the gut microbiome and does it bounce back or
does it then change forever? Where are we in that knowledge? Absolutely. So, you know, I liken antibiotic
exposure to a forest fire. You’re basically getting rid of the vast majority of life that exists in the gut microbiome. And you don’t get rid
of everything because even the most broad-spectrum
antibiotics that we use don’t kill off every single
microorganism in our gut. And that’s also true of the forest fires where those few species
come back right away. Absolutely, absolutely. So it’s very, very similar of a situation. Some of the best work
that we have in the field focusing on how antibiotics
affect the microbiome have actually come here from Stanford from a colleague named David Roman. He and his colleagues did some really transformative early
work in the early 2010s on the exposures of antibiotics
to the gut microbiome in healthy individuals. They took a handful of
individuals, gave them antibiotics, and studied what happened
to their microbiomes. What they found was that, there was definitely a
simplification of the microbiomes when people were exposed to antibiotics. That loss of the diversity
you were talking about. Exactly, that’s loss of diversity and then basically after the
people stop the antibiotics assuming they were living
a healthy lifestyle, which they were, they regained
their diversity, mostly. So that’s good news. Good news. On repeated exposures to antibiotics, what people have observed
is that there may be a point at which you can’t quite
get back to your normal and every time you’re
exposed to antibiotics, you may be readjusting to a new normal. Does the microbiome run in families? So can I assume that my wife and I, our kids are outta the house. That’s a whole different story and I know nothing
about their microbiomes. But do my wife and I
have the same microbiome probably because we’re
spending a lot of time together or could they be very different
even in that home situation? Yeah, so we call the
scientific jargon for this is cohabitating adults.
That’s what I do with my wife. Yes, so you and your cohabitating
adult, your lovely wife, you probably do have some
shared species and strains. So research has suggested
that cohabitating adults do share some strains. There has been some limited
work to show exciting results that people who own
pets, for example dogs, may actually even share a
few strains with their pets. Now this is really exciting
because as you know, there’s this hygiene hypothesis out there and the idea that we’ve
become too clean as a society that’s why we have, like,
asthma and allergies and eczema that are increasing. We need more exposures as youths. Exactly, and we know that people who have animals when they’re young or who live on farms when they’re young actually have a decreased
incidence of these diseases. So one question that has arisen is, “Is it because we’re
actually getting microbes “from these animals around us?” So that raises an issue that I really, I did wanna get to so I’m
glad that you’ve raised this, which is, the role of the gut microbiome
with the immune system. In fact, you would think
they might be at battle with one another but I think
it’s much more complicated and I know you’ve looked into this. So, how should I think
about the relationship of my gut bacteria with the
health of my immune system? Yeah, so we know that animals that can be reared without microbes, we call these germ-free animals. So like the bubble boy
but they’re the bubble cow or the bubble.
Yeah, bubble mouse. Yes.
Bubble mouse. All kinds of bubble animals. So that’s probably easier
than the bubble cow. Yes, but you know, even bubble
fish have been generated. So you can generate these animals without really any measurable microbes and what we know about them, surprisingly, is that their immune systems
are really messed up. That observation actually
suggests that the immune system is really dependent on microbial exposures in order to mature properly. We also know, interestingly, and this is more of a
correlational relationship, that the immune system develops over the first three years of life. You know, that’s why a
lot of kids and babies get their immunizations or vaccinations in that early period of time. That’s actually also when
the microbiome develops. So we know that the vast
majority of microbiome and immune system development happens in those first three years of life. So that suggests that just
like having, you know, a sparring partner, someone who urges you. Keeps you sharp. Yeah, absolutely. I think the microbes keep
the immune system sharp and I think the immune system
keeps the microbes sharp. Okay, so we should be
rooting for a certain amount of healthy competition
between the bacteria and the immune system and
it’s part of developing this robust immune system. Taking that idea and combining
with your earlier comments about there’s many healthy microbiomes, you’ve made a study of the
cultural and geographic diversity of the microbiome including even in places like Africa where I imagine that the lifestyle, the diet, many things are different
from the West Coast of the United States. Why are you doing that work
and what are we finding? Yeah, so the reason we’re doing this work which is really trying to
broaden our understanding of all of the different types of healthy and diseased microbiomes
that exist around the world, is that we know, unlike human genetics, like your human genome
doesn’t really change over the course of your life, we know that the microbiome
can change over life and that the microbiome
is pretty much controlled by your lifestyle and your environment. For example, if you, Russ,
were to move to Greenland and take up a diet that was
entirely of fish and seals, your microbiome would change dramatically. And that suggests that the
variety of lifestyle choices and environmental
exposures that people have can really affect their microbiomes and they affect their microbiomes way more than their personal genetics do. So it’s the environment
is playing a huge role. Even though I’m the same Russ,
after six weeks in Greenland, I’m a different microbiome Russ. Absolutely, absolutely. So one of the challenges
in research has been that we tend to, in my opinion, overstudy kind of the
same people over and over, in part ’cause they’re convenient. Honestly, if I was to do a study of a thousand people’s microbiomes, it’d be a lot easier for me to
do the study here at Stanford and just to recruit, you know,
the incoming freshman class. It would be very diverse. It would be both Facebook employees as well as Google employees. There you go, yeah. And then throw in like
a little bit of Apple just for the fun.
So there’s your diversity. So we know that many of these people are gonna have very, very
consistent lifestyles. And so we thought that
it was really important to broaden our understanding
of all of the different types of microbiomes that
can exist in the world, both for the purpose of better
enumerating what is normal, normal can be a variety of things, but also because, not only should genetic research
be done all over the world, we wanna make sure that
genetic researchers are being encouraged all over the world. So we started this collaboration with a really impressive consortium called the H3 Africa Genomics Consortium. They do a lot of human genetic work and as you know, life
originated in Africa, there’s a huge amount of
human genetic diversity there and we, being kind of
a one-trick pony said, “Hey, we should collect
poop and we’ll sequence it “and we’ll learn about the microbiomes “of these individuals.” Thankfully we have collaborators
who are game for that and we’ve been studying the
microbiomes of individuals in urban township settings and rural areas and trying to understand
how they’re similar and different to each other and
similar and different to us. This is The Future of Everything. I’m Russ Altman, I’m
speaking with Dr. Ami Bhatt about the microbiomes in
Africa and fascinating because of the diversity
and the history of Africa, it is possible that there
will be more diversity of the microbiomes in Africa than there is in the rest of the world or certainly it will be more diverse
than what we’re seeing in local areas as you described. And I also totally buy your argument that if there are gonna be in the future treatments of the microbiome, we really need to understand
the range of normal so that we don’t start
treating people in Africa with microbiomes that are
irrelevant or even damaging. So let me ask that, we hear a
lot about when people migrate from one place to another,
after a certain amount of time they start getting the
diseases of the local milieu. So, you know, we hear
about people from China who come to the U.S. They have a certain diet
and lifestyle in China, and after a couple of generations, they start getting the same heart disease that has been plaguing all of the U.S. Could there be a microbiome
connection to this? Is it that changing your geography is not just the lifestyle
and the McDonald’s and dietary considerations, but that you’re also now
being exposed to microbiomes that might change your disease risk? I absolutely believe so. One of the things that we
don’t know is whether or not a healthy adult can actually
acquire new microbes easily from the environment, but certainly the idea that
changing someone’s lifestyle can change their microbiome
is well established. There have been migration studies where immigrants have been
studied over the course of time. I absolutely think this
is related to disease. One of the things I’m
really fascinated about is this observation that
my parents, for example. My parents came over from India to the United States for school. They were born and raised in India. They could eat all of
the delicious street food that is there. But when we used to go back
to visit when I was a kid, my parents would say, “Absolutely no street food for you,” and absolutely no street food for them, because we would get terrible
diarrhea, to be honest. Why is that so? My parents have been exposed to that.
They’ve grown up on it. Yeah, they’ve grown up on it. Presumably their immune
systems have gotten used to it, so why could they suddenly
not eat these foods anymore? And I really do think part of it might be that their microbiomes
had shifted over time. Fantastic. This is The Future of
Everything, I’m Russ Altman. More with guest Dr. Ami
Bhatt about the microbiome and its significance for
both health and disease, next on Sirius XM Insight 121. Welcome back to The Future of
Everything, I’m Russ Altman. I’m speaking with Ami
Bhatt about the microbiome. And in the last segment
we had a great discussion about health and disease
and immune system. People like to manipulate their microbiome and there’s been a lot of popular press about yogurts and probiotics. Is that all real? How should people think
about the opportunities for manipulating or
improving their bowel health by ingesting foods that modify it? Yeah, so I think it’s natural for us to wanna improve our bowel health. I think almost every
one of us has done this. By the time we’re an adult, we know that there are certain
foods we don’t tolerate, certain foods that actually
work out better for us. I think many people learn, for example, in their 20s and their 30s
that they don’t tolerate lactose anymore, for example.
Right, so milk is out. Milk is out. And probiotics are an
interesting opportunity for us to try and change that microbiome. Can you tell me what is the
definition of a probiotic? Because I think there’s
even confusion about that. It sounds great. Pro, biotic, I mean what
could be wrong with it? Yeah, it’s a fantastic thing, but, it is actually a moving target, also. So, the idea of a probiotic is
it’s live microbial therapy. Right? It’s a compound, not a
compound, but organisms that you can ingest or put on you if they’re skin probiotics. Oh, so there are skin probiotics? There are skin probiotics now, too. So you can ingest or
put these things on you and that they will somehow
improve your health. They can come in a variety of flavors. On one extreme, while fecal
microbiota transplantation is not technically considered a probiotic, it is one of the most complex
live microbial therapies we can administer. Yeah, it’s a definitely cousin idea because you’re introducing
bacteria on purpose to help. Exactly. Most probiotics come in either pill form, so you can go to, often
like the natural foods store and you’ll find an area where
they have a bunch of bottles that are labeled with
different complicated Latin and Greek names. Those are probiotics. Alternatively you can
have things like foods that actually contain live
bacteria or sometimes fungi. On purpose. On purpose. Turns out, this has actually been an important part of
cooking for millennia. Bread, for example, is
obviously fermented by yeast. In the classical way, it was
not just fermented by yeast but also by bacteria that
are present in the air and on the grains of wheat. I believe that’s part
of the sourdough magic is that it’s not just
the yeast but a complex. My son teaches me about
the complex bacteria required for high-quality sourdough. Absolutely, so we consume
bacteria in these ways. Of course, when we bake
bread, the bacteria die but there are things like yogurt. Yogurt is made by actually
culturing milk with bacteria, and we can buy live active culture food. Now, will yogurt automatically
come with bacteria or is it a special type of
yogurt that would have bacteria? ‘Cause I know that people often think, “I love my yogurt, it’s
giving me good probiotics.” I don’t know if that’s true. Yeah, so the majority
of commercial yogurts that are available, the
bacteria have been killed. So if you want to go to the store and buy a live active culture yogurt, meaning a yogurt that still
has living organisms in it, you’ve gotta look for that. They usually say, “live active culture,” and if you turn the
container around to the back, you can actually see the
names of the organisms that are included.
The list of Latin names. Lactobacillus and things like that. Exactly, exactly. Also if you make it at home, of course, you would also be live active culture. So there are other types of foods that are live active culture. Sauerkraut, kimchi, in
fact, almost every culture has some sort of fermented food that’s an important part of
their culture and their cuisine. Yes, we’re overloading the word culture. Every culture has their
favorite bacterial culture. (laughing) Here’s the big question. Is there evidence for health benefit? So this is really where
it gets kind of tricky. It gets tricky because there
have been some big studies done on pills, like probiotic pills, used in the medical setting to do things, specific things, like, prevent antibiotic associated diarrhea. For example, many of our listeners have probably gone to the
doctor, gotten an antibiotic for a bacterial infection, and have been told by either
their doctor or friend, “Hey, eat some yogurt
while you’re having this.” In that concept there is, we know that antibiotic is
killing a lot of the bacteria in your gut, maybe some of
these bacteria from the yogurt will fill in the gaps, and prevent you from having the diarrhea that’s associated with having
low diversity microbiomes. And does that indeed happens? You know, so, there are
studies that say it does, there are studies that say it doesn’t. And I think really, the jury is out. It’s a really complicated topic. As a physician, I would say, there is really limited evidence for the utility of probiotics
in the health setting, and in disease management. So as a physician, it
kind of falls into the, well, I don’t think it’s doing any harm, so I’m not gonna tell you not to do it, but I wouldn’t bet the farm that it’s gonna solve the problem. Absolutely. And I would say in some extreme circumstances of health, like, you know, for example, there have been studies showing that, immunotherapy, which
is a type of treatment that’s used to treat cancer patients, immunotherapy may depend on
what the microbiome contains. We know that there may
actually be risks associated with taking probiotics when
you’re on an immunotherapy agent So that’s a big deal, because now we’re talking about risks. Can you tell me a little
bit more about that? Yeah. Sounds like it’s new. It’s really new. I think none of these
data are published yet. But at conferences, at
scientific conferences, people have been talking
about observations that cancer patients on immunotherapy who are taking probiotics, may actually respond worse
than those who are not. Which really begs the question of, you know, could we
potentially be doing harm by giving people probiotics. So that’s something we’ll
have to keep a close eye on. And I’m sure that oncologists
will pay close attention, because they don’t wanna
undermine their treatments by saying, “oh, it can hurt,” when in fact, maybe it can hurt. So that’s an important one.
Absolutely. This is The Future of Everything. I’m Russ Solomon, I’m
speaking with Dr. Ami Bhatt, about the microbiome. And I wanted to move to
the issue of the microbiome over time and in aging,
folks, which we all are. I think you made a reference to this, that it doesn’t stay the same. So what do we know about
the process of aging? And is there things that elderly people should be thinking about in
terms of their microbiome? I was struck when you were
talking about the immune system, you were very convincing
that people have a good sense of how their bowel is
doing when you ask them. I’m not sure people have a good sense of their immune system when
you ask them in the same way, maybe they do. So it’s all confounded together in my mind as the aging process,
the immune system up, what do we know about that? And what should people be
thinking about as they age? Yeah, so it’s interesting, there’s been a lot of
focus on the microbiome and the immune system in early life, lots of studies on
those first three years. And what we think is that,
for the adult period, people to tend to be pretty
stable in both of those things until later on in life, and our group and others are
actually starting to study, the microbiome of aging individuals. And from animal studies, it’s
actually been demonstrated in the African killer fish model. Killer fish? Killer fish. Yeah. These are really cool, short lived fish. They’re actually the, I believe the shortest
live vertebrate animals. So what are we talking? Months.
Months of life. Months of live. So they really have to go for it. Yeah, they gotta go big, go big and then they have to go home. So an interesting study was done, where they took poop from young fish, and then transplanted it into old fish. And they actually find that
the old fish can swim faster when they have young
poop in them. Am so glad you’ve mentioned this, ’cause I’ve heard about
these kind of studies, and also like old mice giving
their poop to young mice, and vice versa. So yeah, so what’s going on there? You know, it suggests that
there is something within the gut microbiome of
these young individuals that can actually alter the
biology of these animals, older animals, either through their immune system.
They are swimming faster. Swimming faster.
The older fish. So now we just have to figure out what would that mean for a human, and when do I ask for
my young colleague’s, well, I don’t even wanna say it. Yeah.(laughing) So how do we approach this issue? And do we think that there’s
a real hope now for therapies? I mean, are people now
thinking about a future, where in addition to the pills that you’re getting from your doctor, they’ll be interventions to try to spruce up your microbiome? Yeah, I think that there is
a great opportunity here. In part because we know that
there is this association between the alteration of the microbiome and diminishment of the immune system. I think in the future, although there are no
data to support this yet, that older individuals
will get things like, microbial therapies or fiber cocktails that will help keep
their microbiome healthy, and maybe prevent them from
getting things like shingles, you know, a reactivation
of a viral infection, maybe that’s related to our
gut microbiome, who knows? And you’ve made a really
important point here, it’s not just introduction
of the bacteria, but you need them to be happy,
so to speak, and to live. And so you mentioned fiber, because that might be
one of the substrates upon which these bacteria live, in order to stay in your bowel after they’ve been introduced. Absolutely. We can’t just put them there, we’ve got to feed them as well. And so, since fiber is what a lot of these
healthy microbes eat, then we’ve got to feed them. So when we think about high fiber diets, part of the reason we’re
recommending this to patients is not just for the bulk and to help them the
musculature of their bowel, it’s also to have a good relationship with the underlying microbiome. Absolutely. Thank you for listening to
The Future of Everything. I’m Russ Solomon. If you missed any of this episode, listen anytime on demand
with the Sirius XM app.

Leave a Reply

Your email address will not be published. Required fields are marked *