- it all of a sudden hits you, like they're inside you right now. today's scientists are blazing a trail to this very future. - you're actually more microbe than you're human. - [julia] i want to know what breakthroughs are being made. - bio-augmenting our bodies will have a fundamental impact on modern day plagues. - that will forge the future to- for me, that was like, whoa. a disease free world. (intrepid music) (computer beeping) my name is julia ravey. i decided to become a neuroscientist because my nan and several great aunts developed alzheimer's disease. this loss has made me determined to find a cure by any means. i'm fascinated by recent research that links diseases of the brain to microbes in our bodies. and i think this is an avenue that is just coming into its own in terms of research. microbes are tiny living things, smaller than the eye can see. inside the body microbes like bacteria, parasites, and viruses can cause any number of infectious diseases. so what would happen if we just eradicated all of the body's nasty microorganisms? what would the health of society look like? to answer that i want to know how microorganisms cause disease in the first place. so i've come to australia to meet dr. barry marshall. barry's groundbreaking research turned the world's understanding of stomach cancer on its head and won him the nobel prize in medicine. barry is a complete science legend. today barry is hunting a nasty microbe called helicobacter. this bacteria infects the guts of animals and makes them sick. - there are about 30 different kinds of helicobacter. so one of the things i'm planning to do today is go around, get some animal scat. so most of it's kangaroo. - [julia] oh, i'm looking forward to seeing the whole process. i've never seen a kangaroo, i don't think. barry is trying to figure out where helicobacter came from by searching for it in a wide range of animals. - you see those big grassy areas over there. that's where the kangaroos might be hanging out. - [julia] kangaroo! - [barry] so now you've seen one. - [julia] seen one! - [barry] well, i think i can see one. - [julia] oh yeah! - there, there, it looks like it's good enough. - [julia] by analyzing kangaroo feces, barry can get a snapshot of the microorganisms living inside these kangaroos' guts. - you get all different kinds of bacteria that we'll extract the dna and just put all the dna through the computer. - [julia] it was the hunt for helicobacter that led barry and his colleague, robin warren, to overturn what they thought might be a myth, mainly the widely held belief in the medical community that stomach ulcers were caused by stress. - i did have patients who had ulcers and it annoyed me that they seemed to be normal people, but when you couldn't find the cause of their ulcer, you'd always, the medical books would blame it on stress. and i'd say, well these people just seemed to be normal. - [julia] when they looked at patient's stomach ulcers under the microscope, what they found was astonishing. - [barry] these bacteria were unusual. they're curved bacteria. - the infectious agent at work was helicobacter pylori. h. pylori for short is a variation of helicobacter that infects humans. the presence of this microbe in the human stomach upended decades of medical understanding. all of the textbooks said that nothing can grow in our stomach, it's a sterile environment for these types of bacteria, but your findings proved otherwise. - so that became our research project, how could bacteria live in the stomach when there's so much acid? we knew these bacteria were really only human bacteria. so we had to find a human volunteer who could take the bacteria and maybe get an ulcer. - [julia] he had to prove that these bacteria could infect a healthy stomach at all costs. - so eventually i did a self experiment. we decided that i was gonna drink the bacteria, which i did. so we grew the bacteria up in meat broth, like beef soup, if you like, and i drank it down. and then i was having an endoscopy to see if they had colonized my stomach. and after 10 days, the bacteria were there, the infection was taking hold, and they were damaging the lining of the stomach. - [julia] barry was probably the first person to be happy with this diagnosis. - they didn't have any evidence until i did that self experiment. - [julia] barry's experiment was a success, but how can h. pylori thrive in the stomach's extreme conditions? - we found out that helicobacter are unique. they make ammonia and they neutralize the hydrochloric acid so they can survive, nothg else can. - [julia] once established in the stomach, these invasive bacteria lead to ulcers. and if allowed to fester, they can cause cancer. the question became, how could these killer microbes be stopped? - i was excited abt the fa that potentially you could cure something if it's caused by bacteria. - [julia] it turned out that antibiotics can kill h. pylori and cure the ulcers in a matter of weeks. long before the discovery of microbes, scientists had no idea of the role microscopic germs played in human health, but in the 19th century, french scientist louis pasteur developed germ theory, which postulated that microorganisms cause infectious disease, and british surgeon joseph lister found a way to prevent germs from infecting his patients by using antiseptics to sterilize his surgical equipment and clean wounds. but the big breakthrough happened in 1928 when scottish physician alexander fleming accidentally discovered penicillin. penicillin was an mediate cure-all for scarlet fever, meningitis, and even pneumonia. this medication launched the modern era of antibiotics. - i thought it was a great kindness to be able to tell people, no, it's not stress, take some antibiotics and you'll be cured. - [julia] today ulcers are no longer a chnic illness for many, and in the u.s., cases of stomach cancer have decreased almost every year. - like most people, i like to prove other people are wrong. i didn't realize it was going to take 23 years before people really believed it and accepted it. - [julia] by eradicating the microbes that cause stomach ulcers and cancer, barry's research is forging a disease free future before infections even start. (futuristic music) - [futuristic narrator] in the future, the exterior doors of most homes have microbial scanners that detect foreign agents. when people enter the home, the scanner sweeps the entire body for harmful microbes. if detected, a home health robot immediately dispenses the apprriate medication. most people no longer suffer from infectious disease, and doctor's visits are mostly a thing of the past. - [julia] a disease free future like this sounds very appealing. so what would happen if we just eradicated all microbes? to find out, i first want to know exactly what functions they serve. so i've come to amsterdam to speak with biologist and head of the micropia museum, jasper buikx. he has some sobering information about the microbes' role in the human body. - there's about 10 times more microbes in and on your body than you have body cells. so you're actually more microbe than you're human. - that is quite a scary thought. so i'm basically just a carrier for the microbes. micropia developed a technology to help visualize this unseen universe. - this is where you can visit your own microbes. this is you, you're being scanned and we're gonna see who has the most microbes. so every dot that you see here is a microbe, a total of a hundred thousand billion of them. 99% of all those trillions of microbes live in your intestines. these are all digital dots, of course, but we also have them alive. - the staggering number of microbes on display makes my skin crawl, but there's an odd sense of beauty to behold. when you see these under the microscope, moving, all of a sudden hits you like they're inside you right now. that is crazy. the first person to accidentally see these tiny organisms was antony van leeuwenhoek in the 17th century. - he was a draper. in order to test the quality of the cotton and of the threads, he decided to build his own magnifying lenses. and this is what he made. and he was able to reach a magnification of 250 times. - [julia] by looking at everything, from water to the plaque on his teeth, he found the world teeming with all kinds of strange microscopic creatures. - that made him the first scientist, so to speak, to discover the invisible world of microbes. - [julia] but in fact, these creatures have been with us all along. single cell bacteria evolved three and a half billion years ago. they are the oldest life forms on earth. on mars, these microbes exhaled oxygen, which eventually formed our monday atmosphere and created an ecosystem that changed t face of the entire planet. scientists believe our oxygenated ecosystem led to the evolution of multicellular life forms at least 600 million years ago. and this in turn led to the evolution of even more complex creatures, including us humans. in this light, microbes are the most fundamental part of being human. - they digest your foods. they produce all kinds of diffent vitans and hormones. so microbes are essential to our way of life. - [julia] scientists call this vast collection of microbes living in us and on us the human microbiome. - [jasper] in essence, you are a walking ecosystem. - [jia] that's honestly mind owing. each body is a unique walking ecosystem, but how exactly do these trillions of microbes contribute to a person's wellbeing? and how do we get our individual microbiome in the first place? to find out i've come to rutgers uversity to meet biologist dr. maria gloria dominguez-bello. she's researching each person's dynamic relationship with their own individual microbiome. - microbes are a part of us. if we didn't have them, we wouldn't be healthy. we are now understanding that we didn't evolve ale. every animal and plant on earth evolve with bactea in particular. - [julia] like a coral reef or a rainforest, the microbiome is an ecosystem unto itself. - when you have an ecosystem that is perturbed, the first question an ecologists asks is can you restore the ecosystem? - [julia] gloria's understanding of the microbiome started in of all places, the amazon jungle, where she saw firsthand how human microbial ecosystems can quickly change. - i've been working in the amazon for the last 30 years, since i was a student. amerindians have been living there pretty isolated for the last 20,000 years, and i was very interested in understanding the microbiome of traditional peoples. - [julia] through skin, mouth and fecal samples, she measured the impact that external environments in which people lived had on their internal ecosystems. gloria found that those living in the amazonian jungle ha a signicantly hher diversy in the microbes as city dwellers living in instrializ countries. buwhen an dividualrom the remote amazon moved to the city, they quickly lost their microbial diversity. this leads to a startling conclusion. - so that work has shown us that urbanization depletes and destroys the diversity of the microbiome, and in the gut, diversity is good. we know that because diseases decrease diversity. and when you decrease diversity, you cause disease. there is a strong association between high diversity in the gut microbiome and health. - [julia] knowing how vital microbiome diversity is in fighting disease, gloria is investigating how humans acquire microbes in the first place. - [daycare worker] here we go, ah. - and how do babies originally acquire their microbes? - [gloria] inside the uterus, the baby is not being exposed to microbes, but once mom brks water, the baby comes in contact with the birth canal, which is loaded with massive amount of bacteria. - [julia] it turns out the acquisition of microbes starts when a child is born. - by the time the baby's out, the baby's heavily colonized. so it's a microbial baptism. then there's the skin to skin contact. that's the secondary exposure. then the mouth of the mother kissing. it's another exposure. the environment of that baby is heavily maternal and mom is the main source of bacter. that first set of bacteria starts the process of immune education. the immune system will recognize the good bacteria, don't attack. - [julia] but modern medicine is chging the immunity education that comes from this microbial baptism. the rate of cesarean births is increasing. since 1990, c-sections have more than tripled, going from around six percent to 21 percent of all births globally. (baby cries) - c-sections successfully take the baby out, but without passing through the birth canal. this means that c-section babies are born from a sterile uterus into the air of an operating room. - [julia] and gloria has discovered that this may increase the risk of many diseases. - c-section has been associated in humans with increased risk of the modern diseases. for example, an increased risk of asthma, type one diabetes, allergies, and obesity. - starting at birth, the first three years of life are critical in establishing a healthy diversity of microbes. i think it's just fascinating that many new parents are probably quite unaware that the first few years of life are so important for e baby's development of their microbiome. not only that, gloria's research is revealing that the overuse of antibiotics to eradicate harmful microbes early in life is leading to a bigger problem than we ever realized. - we have impacted every step of delopment. the average baby receives 2.7 doses of antibiotics in the first year of life. we have been so successful controlling infectious diseases. but what we didn't know was the collateral damage that was caused to our microbiome. we have increased the risk of our kids to live lives with chronic diseases. we evolved with this biology. we cannot ignore it, because if we do, we are screwing the health of our future generations. - [julia] while helpful in many ways, the sterilization of modern day practices like c-sections and antibiotics could actually be harming on microbiomes, making us more susceptible to disease, but we can't just get rid of modern medicine altogether. antibiotics and c-sections still save millions of lives. so what's the right apoach? gloria has invited me to her home to meet her husband dr. martin blaser. - [martin] hey, how are you? - hi, i'm julia, lovely to meet you. martin is a microbiologist who also researches the microbiome. when it comes to using antibiotics, bothloria and martin believe we need a better balance. - by and large, we have overestimated the value of antibiotics. we're giving antibiotics like water. the big dogma is it might not help you, but it won't hurt. but what if it does hurt? the's more and more evidence we're losing microbial diversity, it's just going down. - [julia] martin and gloria wa to prevt the further loss of diversity in our microbiomes. - we've overdone it. now we have to find a more moderate approach. and ultimately, if we find a more moderate approach, then maybe we can stop the decline in diversity, but how do we get it back? that's gonna require restoration. - [julia] one intriguing candidate for microbial restoration is the h. pylori bacteria, the same one that barry marshall infected himself with. - most doctors in the world are trying to get rid of helicobacter on the idea that it's a bad guy and is. but since then, we've been finding all kinds of good things that the bacteria does. - it turns out that some microbes are double agents and can be both bad and good for the body. what are the good things you found out about h. pylori? - well, we found that people who don't have helicobacter have more disease of their esophagus, and we also found that children who don't have helicobacter have more asthma, and that's really big, 'cause asthma's going up, helicobacter is going down. we think that they're linked. - [julia] though it's been with humanity for millennia, today only five percent of children in the u.s. have the h. pylori bacteria. so if h. pylori can cause stomach cancer, but eliminating it increases rates of asthma, what should we choose? it turns out we may not have to. - i predict that we'll be giving helicobacter pylori back to children so that we can protect them against things like asthma. but we might wanna eradicate it when they're 40 years old so that they won't get stomach cancer. - we have to treat this bug differently in childhood and once you are an adult. - [julia] this revelation shows how we can begin to get the balance right. by treating the microbiome differently at different stages in a person's life, gloria and martin's dynamic approach is the key to eliminating modern diseases. - [futuristic narrator] in the future, nearly every baby is born naturally at home. when c-stions arneeded, babi are batd and incted with microbes taken from the mother's birth canal. from childhood, everyone receives personalized doses of healthy microbes as regularly as vaccines. only prescribed in severe cases, the overuse of antiotics has plummeted. - [julia] if the key to a disease free future lies in managing the balance of good and bad microbes, then what we've put into our bodies will have a huge impact on the microbiome. to better understand how the body's microbes work as a whole, i've come to san diego to meet dr. rob knight. he's looking for ways to create a better balance in individual microbiomes by sequencing their dna. based on numbers alone, this is a very daunting task. - you have about 20,000 or so unique genes in your human genome, but you have millions of genes in your microbiome and all of those microbial genes, we're just finding out about how they make us who we are. - that is incredible that we call ourselves human, but maybe we're not so human after all. - rob's quest is an ambitious undertaking. through the american gut project he co-founded, he's crowdsourcing and analyzing stool samples from across the planet. and because it's an open source project, he'll ultimately share the conclusions of this big data with everyone. for now by sequencing microbial dna from a wide array of pple, rob's pioneering work is diving deeper into the human microbiome than ever before, especially in how our microbes respond to food. in tandem with this, rob's team is also sequencing the dna of the microbes that colonize theoods we eat to analyze and compare its impact on microbes in the human body. - so what diyou collect from the garden today? - so we got another set of fruit and vegetable samples. so rosemary, tomato, eggplant we got today. - great. - [julia] by understanding the microbial big picture, rohas discovered something surprising. - one of the most fascinating and most unexpected things is the particular ways that diet impacts the microbiome. categories that people tnk are gonna make a huge difference, like are you omnivore or you a vegan, are you on the paleo diet, that kind of thing, has almost no bearing on your microbiome results. - this research is coradictinprevailing wisdom. it turns out what does affect the health of our gut microbiome is much more basic and even achievable for most of us. - the things that do matter, turn out to behings like how many different species of plants you ate in the last couple of weeks. things like do you eat a lot of salty snacks or sugary snacks? - wow that is really interesting work. rob's research is showing that eating at least 30 different types of plants per week leads to a more diverse got microbiome. and this matters, 'cause this helps create a better balance of both the beneficial and harmful microbes that are in everyone. this microbial diversity dramatically increases the body's wellbeing, so eat your veggies. but everyone's microbiome is not alike. like a fingerprint, yo gut microbiome is unique and responds differently than others. it even plays a role in how individuals reond to prescription drugs. - one of the major things thate and otrs are trying to find out at the moment is how do you know what medication's gonna work? it turns out that the microbiome explains a lot of that individual variability. - [julia] that's because gut microbes play a role in how medications are metabolized in the body. an individual's microbiome can impact the effectiveness of drugs for parkinson's, high cholesterol, and many other conditions. a better underanding of this cplex relionship coullead to jor breakthroughs inealthcare. - muscle's already being exploited right now for cancer drugs, and so that's a very exciting frontier. - i want to see if there are measures i can take to achieve a better microbial balance today. so i'm conducting a little experiment of my own with a sample kit from the american gut project. which contains tubes and swabs and some gloves. so i think we can all imagine exactly what this is for taking samples of. i'm eating junk food for three days and then a wide range of vegetables for three days. and i'll be taking two samples. after the healthy good and after the unhealthy food and seeing if my microbiome has been altered. oh, i'm gonna be sick, that's horrible. i'm bringing these samples to dr. jack gilbert, the other co-founder of the american gut project. his team is using this research to tease out the body's specific relationship between our microbiome and the development disease. - [jack] what have you brought us? - well, this is a litt bit mortifying. i brought you some samples from a small experiment that i decided to conduct on myself. - okay, yeah. - i want to see if the health of my microbiome improved in the short term. do you think that change could be seen in three days? - it's a little short. (both laugh) - the limitation of time. - precisely. - it's short. - but it's enough to see some changes starting to occur. - [julia] while the samples are processed, jack walks me through the complex relationship between our microbes, food, and disease. - what we found was if you had a stable microbiome that was say promoting obesity, i.e. a micriome that made you fat by producing chemicals which changed your relationship to food, it would take almost a year on a new diet to eradicate those microbes. - wow. - and change it to one that doesn't promote weight gain. that's the problem with diets, nobody stays on them for an entire year. - [julia] also contributing to the chronic disease of obesity, a modern d diet of hhly processed foods can cause the microbiome to become imbalanced. - too much sugar, too much saturated fat is changing the types of bacteria which live inside us. - [julia] to test the relationship betweethe microbiome and weight, researchers took fecal samples from obese mice and transferred these samples into the guts of lean, germ free mice. incredibly this transfer changed the microbiome of the lean mice. after thmicrobiatranspla, the lean mice gained weight and became obese. it turns out that gut bacteria play a big role in reguling the body's overall metabolism. jack believes microbiomes adjusted for poor diets have a similar negative effect on humans, leading to any number of debilitating diseases. - and we think that is having an impact upon things like diabetes and obesity, maybe even depression and anxiety. - similar microbiome transplant studies with mice suggest there is also a connection between the microbes in our guts and alzheimer's. i really interested in the link between the gut microbiome and alzheimer's disease. - you have a family history of alzheimer's. - i do, yes, tt's my motivation for doing a phd in the first place. - so i have the genetic precursors as well. one of the wonderful gifts my mother gave me. - yes, probably mine too. (jack laughs) - exactly. there's a number of different ways that microbes in your gut can affect what goes on in your brain. - [julia] one pathway is the vagus nerve. this long nerve connects the intestines with the brain, creating a two-way channel of communication. research suggests that stress signals from the brain may cause gastrointestinal distress while signals from the gut may alter mood. the brain and guts are also connected by the body's immune system. - and this is very relevant for alzheimer's and parkson's, is the microbes in your gut chge how your immune system works. they can cause inflammation that spreads throughout the body and they can change how the brain is receiving information and how the brain is receiving chemicals. - [julia] jack's research sugges that by eliminating inflammation causing microbes in the intestines through medication or dietary changes, we might prevent alzheimer's disease. - that is a phenomenal change in understanding. - this gives me hope that no one else in my family will have to suffer from this crippling disease in the future. with these neurodegenerative late life diseases, patients often have changes in their brain years before you see any symptoms. do you think we could see an almost microbiome signature of these changes and then jump in with some early preventative measure - i think that is absolutely possible, right? in combination with looking in your blood and seeing if there are biomarkers of the disease, we could also look in your stool and look at the types of microbes which would cause the disease to start progressing. so we may be able to transform our ability to predict it early in the future. - [julia] jack is developing a new technology that will allow people to track biomarkers in their gut microbiomes at home. - this is a mock-up th we're using. - [julia] very nice. - but we've developed a toilet seat, literally just this part of the toilet, that allows for the collection in an automated way of stool and then provide you with updated regular information about the microbes and their functions that are present there, or we might be able to provide you with an updaten what kind of foods you should eat. then we may be able to prevent disease from developing in the first place, by changing what microbes are present in your gut. that would be a phenomenal improvement in our understanding of human health. - [julia] for my short experiment, the fried and fatty junk food had a negative impact on the balance of my microbiome. jack recommends sticking with healthier eating and consuming more fiber. by analyzing, optimizing, and managing our own microbiomes, we could create a future where diseases are kept at bay.

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