Whether they make you fat, fart, or freak out, microbes play a central role in your life. Right beneath your nose—on your face, in your gut, and everywhere in between—trillions of bacteria, viruses, and fungi are so abundant in your body, they outnumber your human cells. But these aren’t just nasty hitch-hikers. Many are crucial to your survival. Evidence suggests that a diverse microbiome can keep you healthy and, conversely, a damaged one could kill you. NOVA Wonders peers into this microscopic world to discover the fascinating, bizarre, and downright surprising secrets of the human microbiome, including the world’s largest stool bank, which transforms raw stool into life-saving poop pills.
NOVA Wonders: What's Living in You?
PBS Airdate: May 2, 2016
TALITHIA WILLIAMS (Mathematician, Harvey Mudd College): What do you wonder about?
ERICH JARVIS (Rockefeller University): The unknown.
FLIP TANEDO (University of California, Riverside): What our place in the universe is?
TALITHIA WILLIAMS: Artificial intelligence.
JARED TAGLIALATELA (Kennesaw State University): Look at this. What's this?
KRISTALA JONES PRATHER (Massachusetts Institute of Technology): Animals.
JARED TAGLIALATELA: An egg.
ANDRE FENTON (Neuroscientist, New York University): Your brain.
RANA EL KALIOUBY (Computer Scientist, Affectiva): Life on a faraway planet.
TALITHIA WILLIAMS: NOVA Wonders, investigating the biggest mystery,…
J.A. JOHNSON (Harvard University): We have no idea what's going on there.
JASON KALIRAI (Space Telescope Science Institute): These planets in the middle, we think are in the habitable zone.
TALITHIA WILLIAMS: …and making incredible discoveries.
CATHERINE HOBAITER (University of St Andrews): Trying to understand their behavior, their life, everything that goes on here.
DAVID COX (Harvard University): Building an artificial intelligence is going to be the crowning achievement of humanity.
TALITHIA WILLIAMS: We are three scientists, exploring the frontiers of human knowledge.
ANDRE FENTON: I'm a neuroscientist, and I study the biology of memory.
RANA EL KALIOUBY: I'm a computer scientist, and I build technology that can read human emotions.
TALITHIA WILLIAMS: And I'm a mathematician, using big data to understand our modern world. And we're tackling the biggest questions…
SCIENTISTS: Dark energy? Dark energy!
TALITHIA WILLIAMS: …of life…
DAVID T. PRIDE (University of California, San Diego): There's all of these microbes, and we just don't know what they are.
TALITHIA WILLIAMS: …and the cosmos. On this episode: the creatures that live on…
MICHELLE TRAUTWEIN (California Academy of Sciences): We have arachnids on our faces.
TALITHIA WILLIAMS: …and inside of us.
PIOTR NASKRECKI (Harvard University): It took 45 minutes for the larva to come out of my skin.
TALITHIA WILLIAMS: But could tiny germs actually be good for us?
KELLY POOLE (C. diff Patient): I said, "Now, these are poop pills?" Who thinks of that?
MONIKA FISCHER (Indiana University Hospital): It's magic!
JACK GILBERT (University of Chicago): It proved that the microbes were playing an active role in shaping our body.
TALITHIA WILLIAMS: NOVA Wonders: What's Living In You? Right now.
Take a look around you. Are you alone?
RANA EL KALIOUBY: Are you alone?
ANDRE FENTON: I don't think so.
TALITHIA WILLIAMS: The room might look empty, but I've actually got plenty of company.
ANDRE FENTON: She doesn't mean me.
RANA EL KALIOUBY: Or me.
TALITHIA WILLIAMS: Besides them, I and all of us have got trillions of companions.
RANA EL KALIOUBY: We're talking about the tiny creatures that live all over and inside of us…
ANDRE FENTON: …microbes…
RANA EL KALIOUBY: …like bacteria…
ANDRE FENTON: …viruses…
RANA EL KALIOUBY: …and fungi.
TALITHIA WILLIAMS: They're so tiny, you can't see them, but there are more of them in and on your body than there are stars in the galaxy.
RANA EL KALIOUBY: More than there are human cells in your body.
ANDRE FENTON: Altogether, each of us are carrying around about three pounds worth. That's about the same size as your brain.
RANA EL KALIOUBY: What are they all doing in there?
TALITHIA WILLIAMS: Today, scientists are exploring this invisible zoo of creatures…
RANA EL KALIOUBY: …discovering, not only how they can make us sick…
ANDRE FENTON: …but how they may keep us well.
TALITHIA WILLIAMS: It's challenging almost everything we thought we knew about human biology. How much power does this microbial zoo have over our bodies and even our brains?
ANDRE FENTON: I'm Andre Fenton.
RANA EL KALIOUBY: I'm Rana el Kaliouby.
TALITHIA WILLIAMS: I'm Talithia Williams. And in this episode, Nova Wonders: What's Living in You? And can you live without it?
PIOTR NASKRECKI: This is a black swallowtail butterfly, one of the most beautiful North American butterflies.
TALITHIA WILLIAMS: Harvard scientist Piotr Naskrecki has studied animals in forests around the world for more than three decades,…
PIOTR NASKRECKI: I just found a nest of citronella ants. They actually smell like citronella.
TALITHIA WILLIAMS: …but bugs are his specialty. And it was a mosquito like this that forever changed his view of what was living inside him.
PIOTR NASKRECKI: I was in Belize, teaching a course in macro-photography, and while there, I was bitten a lot by mosquitoes. After coming back home to Boston, I realized that some of my mosquito bites were not really healing. And when I looked closely, I could see a thin, little straw-like structure that emerges from the wound every now and then to take a gulp of air. And being an entomologist, I realized that this is a breathing tube of a botfly.
TALITHIA WILLIAMS: Botflies are parasites whose larvae grow on animals in the rainforests of Central and South America.
PIOTR NASKRECKI: Because of their very interesting life cycle, they are very difficult to see.
The botfly female catches a mosquito in flight, and holds it, and glues the eggs to the abdomen of the mosquito. When the eggs detect the heat of the body of the host, they immediately hatch, and then they crawl into the hole made by the proboscis of the mosquito.
TALITHIA WILLIAMS: Since botflies never land on their host, he figured the best way to actually see one was to raise the larvae to adulthood, in his own body.
PIOTR NASKRECKI: Obviously, even me, as, as an entomologist, I had this initial reaction of slight, slight revulsion. But that lasted for about three seconds, and then I thought, "What a fantastic chance for me to document it and show it to the world."
TALITHIA WILLIAMS: The larvae spent about three months growing in the skin of his arm, until they were the size of large peanuts.
PIOTR NASKRECKI: I think that the movie Alien got it wrong. A parasite doesn't want to be painful, because a victim that's thrashing, running, ripping things is likely to injure that animal that's, that's emerging from its body.
TALITHIA WILLIAMS: In fact, a botfly actually releases an anesthetic into his host.
PIOTR NASKRECKI: They just pump you with painkillers, so you don't know that you have them, and they produce antibiotics, so the, the wound doesn't fester. It wasn't painful; it wasn't unpleasant; it was very interesting. I know it sounds weird, but I felt an almost, almost father-child relationship with this organism that was growing in my body. It took 45 minutes for the larva to come out of my skin. I prepared a special container, and sure enough, it dropped into that soil, and in about three or four hours, it turned into the puparium, which is, kind of, an equivalent of a butterfly's chrysalis.
TALITHIA WILLIAMS: After six weeks, it finally emerged, and though the botfly would only live for a few more days, its effect has endured.
PIOTR NASKRECKI: The experience of having a botfly made me realize that we, ourselves, are an ecosystem. Our bodies are inhabited by a number of organisms, sometimes permanently or just temporarily.
TALITHIA WILLIAMS: For some, this lesson might come a little close for comfort.
MICHELLE TRAUTWEIN: Would you be interested in seeing your face mites?
TALITHIA WILLIAMS: Michelle Trautwein's research into face mites is part of the growing trend to figure out what exactly is living inside us.
MICHELLE TRAUTWEIN: My research grew out of this natural shock that I had when I first heard that we have arachnids living on our faces.
There it is.
MAN #1 PARTICIPATING IN MICHELLE TRAUTWEIN'S RESEARCH: Wow! They have little, like, legs? Like little appendages?
MICHELLE TRAUTWEIN: What you're looking at there are his four tiny little claws, that they use to climb and hang on into your pores. Here's this long tail, here, which is the perfect shape of a hair follicle.
TALITHIA WILLIAMS: Even though these creatures live, literally, under our noses, we know surprisingly little about their two week lifecycle, because discoveries depend on chance encounters under a microscope.
MICHELLE TRAUTWEIN: Supposedly, they come out of your pores at night, and the males and females have sex on your face, then go back down into the pores to lay the eggs. We actually got to witness the birth of an egg. It's almost like a third of the size of the mite itself. It's the only time we have seen it before, but the truth is that's happening on every human's face, all over the world, all the time, which is incredible to think about.
MAN #2 PARTICIPATING IN MICHELLE TRAUTWEIN'S RESEARCH: So, that's… they're only on your face?
MICHELLE TRAUTWEIN: No, no. They're all over.
I don't think there is anything you can do, in terms of face washing, showering, whatnot, that will get rid of them.
We have two different species that live on us, one a little deeper than the other. So, I like to scrape hard to make sure I get that second species.
TALITHIA WILLIAMS: Michelle's trying to build the largest database of mites and mite D.N.A. ever collected.
MICHELLE TRAUTWEIN: You can't see them with the naked eye.
One mite is about as long as the width of a piece of your hair, about a tenth of a millimeter.
Oh, oh, oh. Look at this. You have got a beauty. Look at that. That's the best one we have seen all day.
MAN #3 PARTICIPATING IN MICHELLE TRAUTWEIN'S RESEARCH: Thank you. I'm an overachiever.
MICHELLE TRAUTWEIN: Oh, my gosh. He's probably been eating some earwax there.
They're not just these, you know, bugs on our face. They have this incredible ability to be storytellers and tell us more about our own history.
As a species, they've been with us since our origins, so they've…you know, hundreds of thousands of years. And I assume that we just inherited them from the ape ancestors before us. But, but the truth is, we don't know.
TALITHIA WILLIAMS: But we do know they've been on Earth hundreds of times longer than we have.
MICHELLE TRAUTWEIN: What's interesting about these two species on us, is that even though they look very similar, they are probably 80-million years divergent from each other, which is probably as closely as bats are related to elephants. I mean they're so distant, it's almost like we showed up to their party. We're really the newcomers here for sure.
TALITHIA WILLIAMS: If you're surprised by mites, you'll be shocked by what else is living in and on your body. Everywhere around us there are trillions of viruses, fungi and bacteria. They live on our skin, in our guts, all throughout our bodies. These creatures make up our "microbiome," the complex ecosystem that calls our body, "home."
JONATHAN EISEN (University of California, Davis): We look around the world, and we see butterflies and trees and cats and dogs. And we see them, and we can understand what they're doing. But the microbes, they're tiny. I mean, they're thousands of times smaller than a millimeter. And that's why we tend to ignore them.
TALITHIA WILLIAMS: The bacteria, in particular, play a key role. These single-celled creatures can be round, spiral or rod-shaped. And while they can make you sick, you might not realize bacteria can also keep you well. They play a vital role in your body, from helping you digest your food to fighting off dangerous invaders. This complicated relationship has been going on since before there were humans, because bacteria have been around from the very beginning.
Imagine that the tips of my fingers, over here, represent the formation of the earth four-and-a-half-billion years ago, and the tips of my fingers, over here, are present day. There's evidence that life in the form of single- celled bacteria first appeared somewhere around my wrist, over here. But it took another three-billion years, around my elbow, over here, before the most basic multi-celled animals evolved. Mammals didn't show up until around the fingers of this hand. And humans? We only appeared in the last millimeter of my fingernail. One swipe of a nail file, and all traces of our existence would vanish.
Microbes have been the most abundant form of life for most of Earth's existence. We've been living with them all around and inside of us and the incredible thing is, for most of our history, we had no idea they were even there.
For millennia, humans struggled to see anything smaller than the width of a human hair, but in the late 1600s, Dutchman Antonie van Leeuwenhoek peered through a microscope and discovered a new universe.
JACK GILBERT: He started looking at little bits of white stuff he found in his teeth; he started looking at water in his backyard. And he was finding tiny little dancing organisms, what he called "animalcules," under these very crude microscopes.
TALITHIA WILLIAMS: To show the world, he made illustrations, images of single-celled creatures, including what we now call "bacteria."
JACK GILBERT: A lot of people didn't believe the drawings. People looked at these and said, "These can't be real. These things don't exist, they would exist everywhere." Turns out, Leeuwenhoek was right, and we were living in a microbial world.
JONATHAN EISEN: Seeing these tiny little things, which they weren't sure what they were, but they could tell that they were alive…it was absolutely a revolution.
DAVID PRIDE: They realized that the human body is more than just a compilation of our own cells, but it's also a compilation of many different, what they called "animal" cells. We didn't have a sense of what they were. Are these things that contribute to human health and disease? We really had no idea at the time.
TALITHIA WILLIAMS: It was nearly 200 years before French scientist Louis Pasteur helped explain what some of these creatures were actually doing to our bodies.
JACK GILBERT: Pasteur proposed this idea called "germ theory." There were organisms in the air that, when they got into a wound or they got inside the body, can make the body turn sick.
TALITHIA WILLIAMS: His theory led to the discovery of specific microbes, or "pathogens" that had caused incalculable human suffering.
JACK GILBERT: Tens of millions of us were dying a year of things like tuberculosis, of measles, of rubella; so much so that people would take photos of their dead children along with their living children, because death was so ever-prevalent. It was so constant in our lives that we accepted it.
TALITHIA WILLIAMS: We didn't understand the process at the time, but there are lots of ways pathogens can make us sick: Vibrio cholera, the source of cholera, secretes molecules that drain fluids and nutrients from the cells of our intestines; Clostridium botulinum, which causes botulism, releases a toxin that blocks neurotransmitters and paralyzes muscles. And microbes have also evolved elaborate ways of manipulating each other.
LITA PROCTOR (National Institutes of Health): There's a whole suite of tools that microbes have to actually kill off or chase off other microbes: they produce a kind of microbial syringe to puncture the cells of other competing microbes or they may produce toxins.
JONATHAN EISEN: These toxins are poisonous to our cells and can make you really, really sick.
TALITHIA WILLIAMS: Casualties of microbial warfare, we were helpless, until an accidental discovery changed medicine forever.
NARRATOR OF ARCHIVE FILM FOOTAGE: In one of the glass dishes where he cultured germs for his experiments, Fleming noticed, one day in 1928, that some mold, had begun to grow.
TALITHIA WILLIAMS: British microbiologist Alexander Fleming noticed that a mold called Penicillium had grown in one of his petri dishes and killed the bacteria he'd been studying. The mold was releasing a chemical that weakened the cell walls of the bacteria, so as they grew larger, they would explode and die. Scientists used the mold to make a miracle drug called "penicillin," and the first antibiotic was born.
JACK GILBERT: You have to understand how transformative this was. Before this, if you got a cut on your finger and it got infected, you could get septicemia. You get a bacterial infection in your blood, it could be fatal.
DAVID PRIDE: Before antibiotics it was, in essence, a coin-flip whether or not you're going to get better.
TALITHIA WILLIAMS: During World War II, penicillin saved the lives of hundreds of thousands of soldiers. It was the dawn of a new antibiotic age, and we developed an arsenal from the natural chemicals that microbes had long used to fight each other.
JACK GILBERT: For the vast majority of time on this earth, it's just been single-celled organisms. And they were fighting like a tiger and a lion would fight if you put them in a cage. They were fighting for space, they were fighting for resources. And they started to produce chemicals to kill each other off. So, antibiotics have been around, we suppose, for billions of years, right? This is not something new.
SCIENTIST IN ARCHIVAL FILM: We have streptomycin, aureomycin, terramycin, chloromycin, arithromycin, magnamycin, bacitracin…
TALITHIA WILLIAMS: Since the early days of discovery, we've produced dozens of antibiotics that cure a huge range of ailments. Fueled by our success, we launched an all-out war on germs.
DAVID PRIDE: It's difficult to think of a breakthrough in human history that's had a greater effect on modern medicine.
RANA EL KALIOUBY: The war on germs is still going on today. Every supermarket is filled with soaps, detergents and disinfectants, designed not just to clean, but to kill germs and keep us safe. But what if all germs aren't all bad? Is it possible that some microbes are actually helpful? Could it be that some dirt is good?
JACK GILBERT: We're going down to the pond. We are going to get enough gubbins in this to make a whole living ecosystem, all right?
CHILDREN WITH JACK GILBERT: Yeah. Yeah!
JACK GILBERT: …like a little terrarium. It's going to be fun.
TALITHIA WILLIAMS: Microbiologist Jack Gilbert has been trying to answer this question for decades.
JACK GILBERT: That's it, put it in there!
When I was a kid, I used to like to make ecosystems in jars, let it create a new world, almost like our planet in a microcosm. And that led me to really love biology. Somebody offered me to go and study bacteria in the Antarctic. I was 21 years old; for me that was an adventure. And so, right there in the wastes of Antarctica, I could understand microbes in the same way as I could understand insects, and birds and animals.
TALITHIA WILLIAMS: Like other creatures, humans are filled with trillions of microbes. Altogether, they weigh several pounds and do everything from producing vitamins to training our immune systems. Scientists like Jack are starting to discover how microbes can affect our health, and lately, his work has taken a very personal turn.
JACK GILBERT: As a father, when my son was diagnosed with autism, I wanted to do something. I wanted to "fix the problem." It took me ages to realize that I couldn't even consider "fixing" my son. He's my son, and he's wonderful and beautiful just the way he is. But what I wanted to do is find ways to use my knowledge of the microbes and their effect upon our bodies to really help children who are suffering from different types of diseases.
The little worms are looking in the holes. Isn't that cool?
TALITHIA WILLIAMS: Jack thinks modern living has isolated us from key microbes that evolved with us over time.
JACK GILBERT: In America, we spend 90 percent of our lives living inside, right? That's crazy; we're an outdoor species. We used to work outdoors nearly all day. We, our kids used to play outdoors all the time.
TALITHIA WILLIAMS: He wants to figure out if these changes to our lifestyle affect our health.
JACK GILBERT: So, I'm very interested in trying to understand the intricate relationships between our microbiome and our body's health and wellness.
TALITHIA WILLIAMS: With so little known about our microbiome, Jack and others are looking for a place to start this exploration.
REPORTER #1: Every three minutes in the United States, someone visits the emergency room with a potentially life-threatening allergic reaction to food.
REPORTER #2: Asthma is one of the most common childhood medical conditions, especially in urban areas.
TALITHIA WILLIAMS: Over the last 20 years, life-threatening allergies in the United States have increased 50 percent, and asthma has gone up by about a quarter. Jack is trying to figure out why these immune-related diseases are on the rise, and he's intrigued by one group that's bucked this trend, the Amish.
JACK GILBERT: Hi. How's it going?
TALITHIA WILLIAMS: When it comes to their health, the Amish are surprisingly similar to other Americans: they vaccinate their children, use antibiotics and have about the same life expectancy, but for some reason, they have half as many allergies as the general population.
DENNIS LEHMAN (Indiana Amish Community): We are taught to live a simple and plain lifestyle, close to God. I think that is the foundation of everything we do or should be. Working with animals is very basic, it's part of us.
JACK GILBERT: The homes are on the farm, I mean yards from the barn. So, the whole family will be working in that environment, pretty much from birth, all right? And that gives them a really large exposure to the microbial world of the farm.
TALITHIA WILLIAMS: There are possibly billions of species of bacteria on the planet, but fewer than 50 regularly make us sick. Jack thinks exposure to many of the other bacteria is actually a good thing, because it can help train our immune systems not to overreact to the world.
The key are "soldier cells," part of the immune system. They travel through the bloodstream searching for bacteria and other foreign objects.
JACK GILBERT: When they find one, they tell the immune system, "Hey, there's something here." And what the immune system does, it comes in with these things called "macrophages," which are like little Pac-Men, right? They "nom, nom, nom." They come along and they munch up the soldier cells and the bacteria.
TALITHIA WILLIAMS: The body then produces more soldier cells that keep looking for foreign targets. But Jack thinks that if a person is not exposed to a wide range of invaders, and the soldier cells aren't kept busy, then, when they do find something, they can overreact, causing allergy symptoms.
JACK GILBERT: What we see, when we look at the immune system of Amish children, is that they have a lot of these soldier cells running around inside their body. And they're constantly being exposed to lots of things all the time, so you have this very active immune system.
TALITHIA WILLIAMS: To see if there's something unusual about the microbes on Amish farms, Gilbert's team exposed lab mice, predisposed to allergies, to Amish dust. Remarkably, they never developed symptoms.
JACK GILBERT: If you can, get it down there in that crack, 'cause then it will collect it.
TALITHIA WILLIAMS: So now, Jack and his research partner, Mark Holbreich want to know what makes this dust so special.
JACK GILBERT: We are using these sampling devices up in the barns, in the milking sheds, even in the house. And then we can collect the dust from this material, which allows us to extract it and find out what microbes are in it.
TALITHIA WILLIAMS: Could a certain combination of microbes protect us? Perhaps ones we've evolved with for millions of years but have now lost touch with in the modern world?
The rise in allergies and asthma is not the first clue that our war on microbes may be causing collateral damage. One of the first signs involved a surprising discovery about another common illness.
ARCHIVAL FILM: Those stomach pains that you talk about, the gnawing, the burning, those are obvious symptoms of gastric ulcer. What I want you to do is to work on your attitude.
TALITHIA WILLIAMS: For years, doctors were convinced ulcers were caused by stress and unhealthy lifestyle choices.
MYLANTA ADVERTISEMENT ACTOR: I started to think there was something really wrong with my stomach.
TALITHIA WILLIAMS: They could be life-threatening, and millions struggled with chronic pain.
MYLANTA ADVERTISEMENT ACTOR: You don't need a prescription, you just need Mylanta.
TALITHIA WILLIAMS: The only relief was antacids, or, in severe cases, surgery.
DAVID PRIDE: I remember my early years as a physician, still going around being taught that ulcers are caused by stress. Hearing other physicians tell their patients, "You need to calm down and be less stressed."
TALITHIA WILLIAMS: But in the early 1980s, Australian doctors Barry Marshall and Robin Warren made a shocking discovery. When they examined biopsies of gastric ulcers, nearly all of them were overrun with this never before identified bacterium, H. pylori. They proposed a new theory that flew in the face of all conventional wisdom. Could this newly discovered bacterium cause ulcers?
BARRY MARSHALL (University of Western Australia, Archival Film Footage): So, we started off trying to make some animal models. We couldn't infect rats, we couldn't infect pigs.
TALITHIA WILLIAMS: Since H. pylori only seemed to infect humans, Marshall used himself as a test subject.
BARRY MARSHALL (Archival Film Footage): Five or six days later, I started waking up at about five o'clock in the morning and running into the bathroom and throwing up.
TALITHIA WILLIAMS: A test showed he was overrun with H. pylori and had gastritis, the precursor to an ulcer. He used antibiotics to kill off the H. pylori and was cured. Proving that H. pylori can cause ulcers was a major medical breakthrough, and, in 2005, Marshall and Warren won the Nobel Prize.
Now, common antibiotics like tetracycline or amoxicillin could be used to help cure most ulcers.
DAVID PRIDE: In the field at the time, there was a saying that would go around, and that was, "The only good Helicobacter pylori is a dead Helicobacter pylori." And that's what all of our efforts were towards doing, was eradicating Helicobacter pylori.
TALITHIA WILLIAMS: A hundred years ago, most people on the planet had H. pylori in their stomachs. After the discovery in the 80s that it could cause ulcers, U.S. doctors wrote millions of antibiotic prescriptions, aimed at killing the microbe. Today, this bacteria is found in only about a third of all Americans, and the number of people suffering from ulcers has declined by 40 percent. But, while ulcer numbers came down, researchers like David Pride were discovering things might be more complicated than they first appeared.
DAVID PRIDE: So Helicobacter pylori has evolved with us for tens of thousands of years, and now that we're eliminating the organism, we're starting to see a different group of diseases pop up.
TALITHIA WILLIAMS: These range from cancer to allergies, asthma and even obesity. But does H. pylori contribute to their rise? Scientists don't know yet, but after decades of waging war against microbes, we can no longer simply look at them as enemies to be eliminated.
DAVID PRIDE: Traditionally, we've thought of microbes as pathogens, so a pathogen being an organism that's going to come into the body, do us absolutely no good and cause disease. But it's a really complicated situation to try and figure out what should we eliminate? How do we eliminate it, and what are the consequences if we eliminate the organisms?
LITA PROCTOR: It isn't a simple, "Remove this microbe and you get rid of this condition." You remove this microbe and then you lose another property that this microbe actually provided to the human host. To me, that's the key takeaway from the H. pylori story.
RANA EL KALIOUBY: After centuries of seeing germs as evil, biologists are discovering it's not so simple.
Take this germ, Escherichia coli, E. coli for short. Like a lot of bacteria, it looks like a tiny, hairy hotdog. This is a hotdog you don't want to eat. It produces a toxin that puts thousands of Americans in the hospital, and kills about 30 every year. But that's just some kinds of E. coli; there are dozens of other strains.
Most of you have some in your gut right now, and they're not hurting you. In fact, a bunch of them are busy breaking down your last meal and producing vitamins your body needs.
Good and bad, they look exactly the same. So, how can we tell the difference? It turns out, the only way is to look at their genes, their D.N.A.
TALITHIA WILLIAMS: At the University of California, San Diego, scientists have collected thousands of oral, fecal and skin samples from donors around the world.
DELIVERY PERSON: Thank you.
TALITHIA WILLIAMS: They're hoping to build a map of what lives in and on us.
After more than a century of studying how microbes make us sick, they want to understand how they can make us healthy, but they can't do it by just looking.
ROB KNIGHT (University of California, San Diego): In the old days, Pasteur could find out there were a lot of bacteria somewhere just by looking down a microscope, but you couldn't really find out what sort were there. In contrast, what we're doing is we're sequencing the D.N.A. of the microbe's genome, so we can tell the kinds of microbes apart.
TALITHIA WILLIAMS: Studying the microbiome in this way has become possible only recently, with powerful supercomputers processing enormous amounts of D.N.A. data.
Lines on the screen show connections between 12,000 donors and the trillions of microbial genes they carry. The goal is to identify the microbes that inhabit us and what combination makes our bodies healthy or unhealthy.
ROB KNIGHT: Can we have a look at this one?
Everywhere we look, every person we look at, we find more and more unique microbial genes where we have no idea what they do, at this point.
…COG3765, about which nothing is known.
TALITHIA WILLIAMS: They're looking to see if lifestyle choices, like where you live or what you eat, affect what lives inside you. And while they don't yet know what a healthy microbiome looks like, patterns suggest the key is balance and diversity.
JONATHAN EISEN: It's not single microbes that have the effect that seem to be important, it's collections of microbes, the number of species that you find in the sample that relates to some interesting health properties.
TALITHIA WILLIAMS: Many new studies have found a connection between microbial diversity and health. After generations of waging war on microbes, these discoveries may revolutionize how we understand and treat our bodies.
Exploration of this new biological frontier is just beginning, and the deeper scientists go into our guts, the more they realize it's not a wasteland at all. It's more like a lush jungle, and, like a jungle, it seems to thrive on diversity.
Healthy people seem to have thousands of different kinds of microbes sharing territory and resources, but if that balance gets disturbed, and certain microbes begin to dominate the jungle, the entire body can be put at risk.
And sometimes, one way to save it may be with a very special kind of transplant.
SAM (OpenBiome Donor): I'm a healthy person. I eat well. I am active. You know, I was fortunate enough to fall into the categories that they're looking for.
TALITHIA WILLIAMS: Sam is one of an elite group of donors for a cutting edge medical procedure that saves thousands of lives. Only three percent of those who apply are approved, a far lower acceptance rate than Harvard.
ZAIN KASSAM (OpenBiome): These are young individuals, on average, around their mid- to late twenties. They are lean. They have a robust diet that's higher fiber content than the average individual.
SAM: Good morning.
ZAIN KASSAM: They really are the Olympic athletes of poop.
TALITHIA WILLIAMS: Sam's donation will be used in a fecal transplant, giving his healthy gut bacteria to a sick patient.
ZAIN KASSAM: Fecal transplants are the closest thing to a miracle I've seen in medicine.
JACK GILBERT: Some people call the fecal microbiome transplant the "brown bullet," like the "silver bullet," but it works.
MONIKA FISCHER: We just know that stool works. We don't know, though, what is in the stool; an extremely complex matter.
DAVID PRIDE: …this sort of biological dark matter, where there's all of these microbes there, and we just don't know what they are.
TALITHIA WILLIAMS: Countless animals eat feces to diversify their gut microbes. Even among humans, the practice dates back to fourth-century China, when patients drank bowls of feces soup. But until recently, it wasn't part of western medicine. Now, a thousand hospitals, in all 50 states get their stool from one company, OpenBiome. And they rely on donors, like Sam, who are paid $40 for each deposit. Each gram of stool contains perhaps 100-billion bacteria and hundreds of millions of other microbes.
The feces is mixed with saline and a preservative, this brown liquid is not heated or sterilized, because the goal is to fill edible capsules with living germs. These pills will be used to treat a gut infection, called Clostridium difficile, that kills nearly 15,000 Americans a year.
Up to three percent of healthy adults have C. diff in their guts. A rod-shaped bacteria, its many long legs, called "flagella," can help it colonize the gut quickly, if given the chance.
ZAIN KASSAM: Clostridium difficile is a bacteria that lives in your gut naturally, but it's kept at bay because of all the good bacteria. The challenge comes when you have antibiotics for many other reasons and that kills a lot of the good bacteria that were out-competing C. diff, and then C. diff can kind of run rampant.
TALITHIA WILLIAMS: That's exactly what has happened to Kelly Poole after taking antibiotics for dental work. Now, she has a C. diff infection that's been utterly debilitating.
KELLY POOLE: I've been pretty miserable. The stomach cramps and just the overall, just the pain. I didn't leave my house for two or three weeks, because all of a sudden, it's like, you don't even know you have to go to the bathroom, you have to go to the bathroom right now. So, I mean, it's glamorous.
ZAIN KASSAM: C. difficile is really hard to treat. In fact, "difficile" means difficult in Latin. Antibiotics work on the order of magnitude of about 40 percent of the time, but fecal transplants work about 89 percent of the time. That's tremendously effective. Not too many things in medicine work nearly 90 percent of the time. So, I think what we really have to do is start to question our assumptions of what is disgusting and what we feel about that.
TALITHIA WILLIAMS: Even though they are the main source of the problem, more antibiotics are the usual treatment for C diff infections. But after taking multiple courses, Kelly is still sick, so she's come to see Dr. Monika Fischer at Indiana University Hospital.
MONIKA FISCHER: Okay, in and out.
Why is this C. diff epidemic happening?
Good. Just normal breathing.
Because, certain C. diff strains developed resistance to antibiotics.
TALITHIA WILLIAMS: Antibiotics kill most bacteria, but like any creature under attack, some of the fittest will survive. These reproduce and create a new, resistant generation that can't be killed by antibiotics. In the animal world, the process of natural selection can take millions of years, but bacteria can evolve resistance in only minutes.
JONATHAN EISEN: By putting antibiotics onto a little growth plate with different doses of antibiotic, you can watch in nearly real time, as individual microbes evolve resistance. So, you have Dose Number One, kills most of the microbes that are in that region. But, eventually, a few of them can evolve resistance to that antibiotic, and then they can spread up to the strip of the plate where Dose Number Two is.
TALITHIA WILLIAMS: This strip has a higher dose of antibiotics, but soon it and even higher doses will lose out to new resistant strains.
JONATHAN EISEN: They spread across Dose Number Three, and so on. And that's how you can visualize an evolution of resistance to antibiotics.
TALITHIA WILLIAMS: In a dangerous cycle, more antibiotics lead to greater C. diff resistance. And, making things worse, antibiotics also kill off the diverse microbes that usually keep C. diff in check.
KELLY POOLE: So, I was on amoxicillin for, like, five days.
MONIKA FISCHER: I see.
KELLY POOLE: And then my doctor…
MONIKA FISCHER: Many of us take antibiotic, you know, for all kinds of reasons. And we all think about killing the bad bugs, right? But we are forgetting about that we are killing the healthy, useful bugs in our colon as well.
MONIKA FISCHER: The amoxicillin, the antibiotic you took, destroyed your healthy bacterial communities in the gut. So, the antibiotics against C. diff don't work, right? So, we have to do something different.
KELLY POOLE: I thought maybe, you know, she had some secret magic pill. It turns out she does.
MONIKA FISCHER: I am recommending that you undergo a fecal transplant.
KELLY POOLE: What is a poop transplant? I've never even heard of that. Who is a poop donor? Who thinks of that?
MONIKA FISCHER: I'm actually lucky to be able to offer it in the form of a capsule, because previously we only could offer it via colonoscopy or enema delivery.
KELLY POOLE: All right, I just have to take a pill and we're done. And she's like, "No, it's 30 pills, all at once." So, that's a little hard to swallow. Maybe it's going to be a little hard to swallow but…And then I said, "Now, these are poop pills? Pills of poop?" And her response to me was, "Well, it's a hundred percent natural." So, there you go.
TALITHIA WILLIAMS: Taking the pills will work something like an organ transplant, though in this case, the organ will be an entire community of microbes recolonizing an essentially empty gut.
KELLY POOLE: It's weird. There's no doubt about it, it's weird. But one of the doctors told me the Chinese have been drinking a poop soup for a thousand years. Drinking poop soup, that's weird. That would make me squeamish. Taking 30 pills, as disgusting as it may sound, as obscene as it may sound, I don't know why you would not do it.
ANDRE FENTON: You can't blame Kelly for being a bit grossed out. We're taught from the time we were toddlers not to touch poop, never mind eat it! And yet, in some cases, doing the gross thing might be the healthy thing. And in a certain way, it makes sense to transplant the healthy gut of one person over to another.
But it is risky, because researchers are only just beginning to unravel all the intricate connections between our microbiome and our bodies, connections that may reach far beyond our bowels and even to our brains.
TALITHIA WILLIAMS: A series of groundbreaking experiments began in 2004. Scientists at Washington University took fecal bacteria from an obese human and gave it to a mouse. The mouse became obese, and our understanding of the power of what's living in us changed forever.
JACK GILBERT: I can't tell you how incredible that was. It was a seminal discovery. It was, it was so important for our field, because it proved that the microbes were playing a role, an active role in shaping our body.
LITA PROCTOR: It opened up all kinds of potentials. You could test all kinds of things. Now you could transfer human microbes to mice, and to elicit a change in the mice? To me, that was amazing.
TALITHIA WILLIAMS: Soon, researchers began to study the effect of the microbiome on nearly every part of the body, even the brain. Our brains are directly linked to our guts through one of the longest nerves in our bodies, the vagus nerve. It helps regulate a wide range of involuntary functions, like heart rate and digestion. And now, scientists are discovering that microbes can affect what travels on this neural superhighway.
JACK GILBERT: Certain bacteria produce neurotransmitters in our gut, which are sensed by our gut environment and actually send signals up to our brain, changing brain chemistry in our heads. So, things like depression, anxiety, autism; things like Alzheimer's and Parkinson's; other neurodevelopmental conditions, even A.D.H.D., could be related to gut bacteria.
TALITHIA WILLIAMS: Sarkis Mazmanian is trying to understand this brain-gut connection. He works with some of the only bacteria-free creatures on the planet, germ-free mice. Though they're vulnerable to disease, they can live a normal lifespan, if they stay in their bubbles.
SARKIS MAZMANIAN (California Institute of Technology): These animals are called "gnotobiotic" or germ-free animals, and they're devoid of all microorganisms. And so, this allows us to add back any microbe that we want and look at the effects of that microbe on the animal.
TALITHIA WILLIAMS: Sarkis decided to test the effect of the microbiome on the brain, because certain neurological diseases have a surprising connection to gut disorders, diseases like Parkinson's.
SARKIS MAZMANIAN: Upwards of 80 percent of Parkinson's patients exhibit severe constipation. In most cases, the constipation presents itself years, if not decades before the first onset of motor symptoms.
TALITHIA WILLIAMS: Could microbes trigger the symptoms of Parkinson's disease? To find out, he's transplanted gut bacteria from humans with Parkinson's into the mice. They stumble and shake as they cross a balance beam.
SARKIS MAZMANIAN: Patients with Parkinson's will have tremors or altered gait, hunched posture and other physical motor impairments. And those mice develop all of the features of Parkinson's: both the underlying pathophysiology, as well as the motor symptoms.
TALITHIA WILLIAMS: But when he eliminates the bacteria, the symptoms disappear.
SARKIS MAZMANIAN: By removing the gut bacteria, we showed that the symptoms of the animals improved dramatically, to the point where we didn't see any detectable motor symptoms in these animals. The study showed that the microbiota was involved in those symptoms. Now, whether or not the microbiota is driving or can ameliorate or reduce symptoms in human Parkinson's still remains unknown.
TALITHIA WILLIAMS: It's possible that a molecule produced by a bacteria in the gut could be sending signals to the brain, through the bloodstream or nerve connections, triggering the symptoms of Parkinson's. For now, the mechanism remains unknown.
To further explore the connection between the gut and the brain, Sarkis is looking at another disease associated with digestive problems: autism. He works with mice that have autism-like symptoms, like repetitive marble burying.
SARKIS MAZMANIAN: The features of autism include repetitive behavior. An animal that has this compulsive behavior, once they bury a few marbles, will feel compelled to bury the next one, and the next one, and the next one.
TALITHIA WILLIAMS: Sarkis looked at the intestines of these animals and discovered they had a condition known as "leaky gut." An emerging theory is that, in those with leaky gut, the walls of the intestines become more permeable, allowing potentially harmful particles produced by microbes to pass into the bloodstream. And this might shed light on autism.
SARKIS MAZMANIAN: We were really excited, because children with autism also exhibit leaky gut.
TALITHIA WILLIAMS: And when the team gave the mice a bacteria called B. fragilis, believed to help seal gut walls, something amazing happened.
SARKIS MAZMANIAN: When we carefully selected organisms from the human microbiota, and introduced them to the mice, not only did we see improvements in their gastrointestinal symptoms, but we saw improvements in marble burying.
TALITHIA WILLIAMS: The treated mice buried significantly fewer marbles.
SARKIS MAZMANIAN: Using the mouse models, we've been able to reverse the symptoms of autism through the microbiome, but I think it's important to remember these are still early days in research. All mouse models are inherently limited, because they're not the human condition.
TALITHIA WILLIAMS: It's too early to know what his discoveries mean, simply because: mice are not human.
JACK GILBERT: What we do in animals doesn't always translate to human beings, but we know that your body is a massive, interconnecting, vibrant ecosystem of life, right? So, when one thing changes, it changes other things.
NURSE #1: (Indiana University Hospital): Kelly?
TALITHIA WILLIAMS: We're just beginning to glimpse the countless ways bacteria might be affecting our health, but there's already one microbiome treatment that is consistently effective.
NURSE #1: Thank you.
TALITHIA WILLIAMS: In Indiana, Kelly Poole is ready for her fecal transplant.
NURSE #1: So, we're ready to do the capsules. I'm going to go downstairs and get them. They're stored at minus-70 C, so they're going to feel really cold going down.
KELLY POOLE: Okay.
TALITHIA WILLIAMS: To preserve the bacteria, the pills have been in a deepfreeze since they were manufactured at OpenBiome in Boston. The microbes aren't affected by the cold.
NURSE #1: All right, Kelly, are you ready to take the capsules?
KELLY POOLE: Sure.
NURSE #1: Here's some water.
KELLY POOLE: That's a big pill.
NURSE #1: I would recommend not swallowing more than two at a time, but…
KELLY POOLE: Two at a time?
NURSE #1: Just do one.
KELLY POOLE: I'm going with one.
NURSE #1: Yeah. Take your time. You have…
TALITHIA WILLIAMS: Within minutes, the capsules will open in Kelly's stomach.
KELLY POOLE: You are opening your body up to some risk, and my understanding is, because this is new, they don't know the total story. But on the plus side is, you know, that it's been tested to make sure it doesn't have certain diseases.
That was a big one.
TALITHIA WILLIAMS: Because there's so much unknown about the relationship between the microbiome and a range of illnesses, the best OpenBiome can do is eliminate donors who might inadvertently transfer something unwanted.
ZAIN KASSAM: The screening process is very rigorous. We look for G.I. diseases; that's kind of an obvious one, for sure. We know there's a connection between the gut and the brain, so we look for psychiatric diseases. We look at obesity; cardiac history and things that we know are very strongly related to the microbiome, like inflammatory bowel disease and colorectal cancer.
NURSE #1: Does it taste like anything?
KELLY POOLE: Unh unh.
LITA PROCTOR: You shouldn't be too surprised how little they know.
KELLY POOLE: There's no taste, but I'm not letting it stick around in there very long. Would you?
LITA PROCTOR: We're very, very early days yet, in this field. These microbes act in communities. We haven't a clue how they interact with each other.
SARKIS MAZMANIAN: We harbor bacteria and viruses that may not cause disease in me, but when transferred to an individual with a different genetic makeup, may affect them adversely.
MONIKA FISCHER: I mean, it's pretty crazy isn't it? That we have no idea what's in the stool, right? We just do it because it works. There's a hundred-trillion bacteria in there; there are viruses; there are fungi. We don't really know what is helping. So, it's pretty amazing stuff.
KELLY POOLE: Last one.
NURSE #1: One more.
KELLY POOLE: Wow, that was the hardest one.
NURSE #1: You did great.
NURSE #2 (Indiana University Hospital): You did great. Awesome!
NURSE #1: Make sure you can feel all the pills go down.
KELLY POOLE: Oh, they're down.
TALITHIA WILLIAMS: After C. diff took over her gut, Kelly was unable to leave home for weeks and visited the bathroom dozens of times a day, but within 24 hours, the healthy donor bacteria has started to balance out the C diff, and her symptoms are gone.
KELLY POOLE: You just wake up, and you go to the bathroom the next day, and it's glorious.
MONIKA FISCHER: For me, it's magic. How wonderful that is, that you just take healthy human waste, right, and save someone from dying? And they can put the C. diff misery behind.
DAVID PRIDE: We're sort of a large superorganism. And now that we know that these microbes, particularly the bacteria, are contributing to us in so many different ways and have been evolving with us for so many years now. It sort of changes our outlook on ourselves, where we realize it's not only important that we keep ourselves healthy, but it's important that we keep our microbial communities healthy as well.
JACK GILBERT: We are the frontier of research and development into the roles the microbiome can play in helping us to treat disease and make people healthier. Everything from autism, depression and anxiety, could be related to the microbiome, so, I have hope that we are going to develop therapeutics which will change lives in the future.
CHILDREN WITH JACK GILBERT: That's an ecosystem.
JACK GILBERT: That's a perfect little ecosystem.
CHILDREN WITH JACK GILBERT: We need some fishies.
JACK GILBERT: We got lots of things that are alive in there. We've got insects; we have invertebrates; we've got bacteria; we have archaea; we have fungi; we've got everything. It's an entire world!
Rana el Kaliouby
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This program was produced by WGBH, which is solely responsible for its content. Some funders of NOVA Wonders also fund basic science research. Experts featured in this film may have received support from funders of this program.
Original funding for this program was provided by the National Science Foundation, the Gordon and Betty Moore Foundation and the Alfred P. Sloan Foundation.
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- Jonathan Eisen, Rana el Kaliouby, André Fenton, Monika Fischer, Jack Gilbert, Zain Kassam, Rob Knight, Dennis Lehman, Sarkis Mazmanian, Kelly Poole, David Pride, Lita Proctor, Michelle Trautwein, Talithia Williams