Let Them Eat Dirt | Dr. Brett Finlay | Talks at Google

Thank you, Maria. And thank you all for coming. She's already got half the talk done, so it's perfect. That's kind of the concept I want to discuss today. We'll talk about kids, but I'm also going to talk about microbes affecting not just kids, but people of other ages, including the elderly. My career, I've worked a lot on diarrhea, salmonella, E. coli. So I warn you I have a perverse sense of humor. That's why we're restricted for fecal content here. When you think about what's important to this world, you might think of a yacht or a diamond ring, but really, the important things are kids because they're our future. By the time I end this talk, I want you to think of kids more like this, coated in microbes. As Maria said, we've known there are microbes in and on us for a long time. Antony van Leeuwenhoek in the Netherlands was a passionate lens grinder. He built microscopes and looked at things. He swabbed his mouth and teeth, held it under the microscope, and saw all these animalcules. He made the stunning observation that there were more microbes in his mouth than all the people living in Holland. This was 330 years ago, and no one believed him. But over time, they sent someone to look, and he was right. That's when microbiology was discovered. Microbes play a big part in this world. They were here long before us. They built the oxygen we breathe. We only think about the big ones, plants and animals, which are a tiny portion of the tree of life. They were here long before, so they'll be here long after us. These things were discovered 330 years ago, but they had no idea what microbes do. Then Louis Pasteur and Robert Koch, one German, one Frenchman, competitors, showed that microbes cause infectious diseases. That was a big finding. They showed that cholera, anthrax, and tuberculosis caused disease. Pasteur also showed that if you cooked these things, you killed them. Pasteurization. This was 125 years ago. It meant that if we killed these microbes, we wouldn't have disease. So society went on a huge kick to get rid of microbes. In World War II, antibiotics were invented. They could save lives. We brought in sanitation, got rid of rats, had garbage collection. We went on this bandwagon to get rid of microbes because they cause disease. Now we have things that kill 99.9% of bacteria. It worked beautifully. In the 1914 to 1920 era, 30% of kids less than one year of age died of infections. Now less than 0.1% do. Clean is great. Infectious diseases have gone down. We have vaccines, antibiotics, we've cleaned up our world. I worked on infectious diseases, so I look at this curve and think, this is not a growth industry. But this is only the first half of the curve. The second half is so telling. In the same 50 years, look around the world. People now have asthma, diabetes, obesity, inflammatory bowel disease. These are Western society diseases. What has happened in 50 years? That's two genetic generations of humans. It takes a hundred generations for genetic changes. So we've not evolved in 50 years. We've done something to our world. The concept I'm going to try to get across is that we've gotten too clean. These microbes are influencing the diseases that affect us daily. You are more microbe than you are human. The number of microbes in and on you outnumbers the number of human cells. They contain 15 times more DNA than Homo sapiens. These microbes have a big influence on us. New sequencing technologies have allowed us to characterize these microbes without having to streak them on a plate. In the mid-2000s, the Human Genome Project came online. We sequenced the human genome. But once they finished, they looked at each other and said, what are we going to do now? Someone said, let's sequence microbes. There are lots of them. That turned into the Human Microbiome Project. It's been a stunning generation of data. There are a hundred trillion microbes in and on your body, 10 trillion in the gut. To put that in perspective, one gram of feces contains more microbes than all the people in the world. I brushed my teeth really well, swabbed a cheek cell, put it under a microscope, and stained it. You see this gorgeous cell, that's me, but look at all the microbes stuck to it. That's just normal mouth. These critters are wherever your body is exposed to the environment: on your skin, in the oral cavity, the gastrointestinal tract. They increase in numbers as you go down. The highest numbers are in the lower bowel and lower intestine, where there's no air. Each of these places is a different environment. The microbes on your armpit are very different from your scalp. Everyone has a unique composition of microbes. Genetically, we're 99.9% the same, but there is no single microbe found in all people. Each person is at best 50% the same as someone else. So when we talk about personalized medicine, I argue we should talk about the microbes because that's what's really different between people. What do these things do over life? That first magnificent moment when you're born, your mother gives you your very first birthday present, a big bolus of fecal and vaginal microbes. Gross, but it's really important. That's when you kickstart your body for these microbes. As the kid inhales and eats, the number of microbes increases. It bounces around in early life, then hits a kid microbiome that stays pretty constant until puberty. Then hormonal changes give you an adult microbiome. Your microbiome is pretty constant from puberty until about 65, unless you do something like move to another country, become a vegetarian, or swear off alcohol. At the other end of life, post-65, your microbes fall off a cliff. There's a lot of influence of these microbes in terms of aging. There's hope that we can influence aging by improving the microbes. Do we need these microbes to live? Yes. The experiment has been done in both people and animals. David Vetter, the bubble boy, was a kid in California. Before he was born, they knew he wouldn't have an immune system. They birthed him by C-section, put him in a sterile container, fed him sterile food and water. He would have died except they fed him essential vitamins that microbes make. He spent 12 years in a bubble and died at 12 of an infection. In animals, we do similar experiments with germ-free animals. We're learning that these microbes affect how the brain develops, how the gut develops, how the immune system develops. They are normal pieces of us that we need to develop normally. Do they have any effect on disease? This is where it gets really interesting. Look at this list of diseases: all the Western society diseases. The microbes in the disease patient are different than the healthy ones. That doesn't prove it's causing the disease, but there's an association. In some cases, they seem to be contributing significantly to the disease. Can we use that therapeutically? Yes, you can do a fecal transfer. There's an infection called Clostridium difficile, or C. diff. Let's say you're old, you go to the hospital for a hip transplant. The surgeons fill you up with antibiotics. Antibiotics carpet bomb the microbes. The idea is to get rid of the microbes so if the surgeon slips, you don't get infections. But you're killing the good ones with the bad. That creates a niche for C. diff to crawl in. It's very competitive. This has been a big cause of death. People go to the hospital for an operation and die from this. It's a disease caused by antibiotics. How do you treat it? They give them antibiotics, which treats maybe 20% of this fatal disease. Someone reasoned that if we could replenish the feces in the gut, we might be able to boot it out. They did fecal transfers, either by nasal gastric tube or enema. There are even YouTube videos on how to DIY. Do not do this yourself because if you perforate your bowel, you will die. But the neat thing is that with this disease, it cured 94% of these people by simply putting healthy feces from a different person into the diseased person. That's fantastic. We can start to think about treating diseases by changing the microbes. Let's spend more time talking about kids because this is where the microbes seem to have a major influence. As a kid is born, the microbes bounce around the first two to three years of life. By about three years, the microbes are pretty stable for their childhood. One of the key roles of these microbes early in life is to help our immune systems develop normally. Germ-free animals have really whacked immune systems. Several studies show that they help the immune system develop a balance, so it knows which way to go. If it goes too far, you get allergic or autoimmune diseases. I'll tell you a story that came out of our lab dealing with asthma. When I was a kid, nobody had asthma. We had one kid in school with asthma, so he must have been a mutant. Now, you go to the playground and kids take a puff from a puffer and pass it to a friend. 20% of kids have asthma in just a short two-generation time period. When you look at asthma worldwide, it's a developed country disease. We see it in Canada, the US, the UK, Australia. It's associated with something that changes in the world. There are all sorts of hypotheses about what triggers asthma. We certainly know it's gone way up in a few years. Here are a few things that affect your outcome of asthma. If you live on a farm, you have a 20% less chance of getting asthma. If you're born by C-section, you have a 20% more risk than if you're born vaginally. Asthma doesn't kick in until five years later. How does how you come into this world affect how you come out? The microbes in C-section kids are different. Vaginally born kids have the mother's vaginal microbiome, which is important for breaking down breast milk. C-section kids have microbes like the mother's skin. If you have antibiotics in the first year of life, you have a much higher rate of asthma. What do antibiotics do? They affect microbes. If you're breastfeeding, you have a reduced rate of asthma. What do all these things have in common? Microbes. I had been using antibiotics to affect diarrhea outcomes in mouse models. I came home one night and was talking to my wife, Jane, a pediatrician. I said, 'If we treat these mice with antibiotics, we can shift the microbes and affect their diarrhea.' She said, 'That's interesting because there are studies on antibiotics early in life affecting asthma.' That comment stuck with me. Being the good husband, I didn't believe her, so I looked it up. Wives are always right. She was right. But I couldn't find the experiment that proved microbes were causing asthma. There were correlations, but not proof. So we did the experiment. I had a bright young grad student, Shannon Russell. She came bounding into my office to plan a project. She was probably thinking we'd work on E. coli or Salmonella. I said, 'Let's work on asthma.' She said, 'Okay, sure.' We started with simple experiments. We treated mice with antibiotics, used a mouse asthma model, and saw if we could affect the outcome. We took mice very early in life or adult mice, treated them with antibiotics, and induced asthma. In the early ones, still breastfeeding, shifting their microbes with antibiotics led to profound rates of asthma. The guy I worked with at the asthma lab had never seen rates like this. But if we did it to adult mice, we saw no effect. So we said, let's do it in kids. We grabbed a cohort of 200 Canadian kids. They had been looking at risk factors for asthma, like a smoker or a dog in the house. I called them up and said, 'Collect the feces.' They said, 'Oh god, it's Finley and his feces again.' But they started collecting feces of three-month-olds and one-year-olds. We looked at the feces at three months and one year. We found that if a three-month-old had four specific microbes, that kid would not go on to get asthma. If the kid did not have those microbes, they were at high risk for asthma. By the time they got to one year, it didn't have any effect. We did a fun experiment where we took a germ-free animal, put in feces from a three-month-old who went on to get asthma, and then spiked in those four bugs. Putting those four microbes into the human feces and into the mouse blocked mouse asthma. That's as close as we are to showing these things play a role. You could test a kid's microbes, and if they don't have these four, you could think about a probiotic intervention. We're not there yet, but that's where we're heading. What about other problems like obesity? Obesity is a major problem. Pediatric obesity has gone through the roof. Three- and four-year-olds are obese. What do microbes have to do with it? Everything. Jeff Gordon did some neat experiments. He took a fat mouse and did a fecal transfer to a thin mouse. The thin mouse got fat. He took a thin mouse and did a fecal transfer to a fat mouse. The fat mouse got thin. He took fat people's feces, put it in thin mice, and they got fat. The microbes seem to be controlling this. It makes sense because the microbes break down what you eat. In obese animals and people, the microbes are really good at generating extra energy per unit of food. The microbes from thin people are kind of wimpy at it. There's an Israeli friend of mine who started a company called DayTwo. He made a bunch of Israelis wear glucose monitors and monitored their microbes and food. Glucose spikes lead to obesity and type 2 diabetes. He mapped all these microbes and food types. Based on that, he can analyze your feces for $300 and tell you what foods to eat based on your microbes. Some people can eat as much ice cream as they want without glucose spikes. Others can't. Each person is different because they have different microbes. When compared head-to-head with standard diets like Atkins or Weight Watchers, it works great. I think we'll see personalized diets based on your microbes. Another major disease is inflammatory bowel disease, Crohn's and ulcerative colitis. Your gut is on fire. Because it's the gut, there are microbes associated with it. They've been doing fecal transfer experiments. Sometimes it works, sometimes it doesn't. That makes sense because we don't know what the perfect donor is yet. With IBD, we have to figure out whose stool has the magic juice. The only adverse effect correlated with a fecal transfer so far is a thin woman who had IBD and an obese healthy sister. The obese sister donated her feces, the thin woman got better, but she also got obese. Now the sister is suing the other sister. An area I know and love is diarrhea and microbes. We've talked about C. diff. We've done experiments with salmonella and E. coli showing that microbes influence the outcome of disease. We're working on preventing diarrhea. The most profound area of interest is the brain. Germ-free animals' brains don't develop normally. There are studies showing that you can take a depressed, stressed, or anxious mouse, put its microbes into a normal mouse, and the normal mouse becomes stressed, anxious, or depressed. There are hints about autism. Autistic kids have different microbes, but they might be eating differently. There are a few one-off fecal transfers where an autistic kid seemed to improve behavior. A study last week did fecal transfers on 18 autistic kids and saw major improvement at eight weeks. So microbes might be influencing the brain. They are influencing many childhood diseases. I think there's only one baby in the audience, but I want to talk about other aspects of life too. Here are the top 10 reasons you're going to die, from the CDC. How many of these are infectious? One: influenza and pneumonia. How many are linked to microbes? Nine out of ten. Heart disease, cancer, lung diseases. You may think I'm crazy, but there's starting to be nice data. Take cardiovascular disease. For a long time, it's been associated with red meat. When you eat red meat, microbes take a component called phosphatidylcholine and convert it into TMA. Your body then oxidizes it into TMAO, which causes atherosclerosis. If you take a germ-free mouse with no microbes and feed it red meat, it doesn't get atherosclerosis. Vegans and vegetarians have very low rates. The most exciting study was when they made enzymes that blocked the microbial enzymes that do that first step. They tested it in a mouse model and could block it by drugging the bugs. They've been trying to drug the second step in the liver, but all the drugs have been toxic. The funnest experiment was when they convinced a vegan who had never eaten a steak to eat one. Because the vegan never had steaks, they didn't have the microbes to do that conversion, so nothing happened. The only one on the list I couldn't attribute to microbes was accidents. A big study from the UK correlated antibiotic use with anxiety and depression. More courses of antibiotics, the more anxious and depressed you'll be. Antifungals and antivirals had no effect. We talked about autism and ADHD. Jet lag. I just came back from Europe. It sucks. The same Israeli guy convinced his grad students to go to meetings around the world, collect their feces, be jet-lagged, and come back. He flew business class, so no grad student would say no. It turns out microbes have a big influence on circadian rhythm, which is what jet lag is. By affecting microbial composition, you can affect circadian rhythm. I'm dying for the day when you take a probiotic before going to Europe and feel normal. This whole gut-brain axis, these microbes are talking to the brain and the brain is talking to the microbes. Major issues are degenerative brain diseases like Alzheimer's and Parkinson's. As our population ages, they become more prevalent. There are things you can do that have a microbial link. There's a diet called the MIND diet, a modified Mediterranean diet. It's a glass of red wine, fruits, vegetables, legumes, nuts. Studies showed that if you ate this diet, you could decrease your risk of Alzheimer's by 50%. If you didn't stick to it perfectly, you could decrease it by 25 to 30%. Diet plays a big role in dementia and Alzheimer's. The lowest rates of dementia are in rural India, which has a higher microbial rate. If you brush your teeth three times a day, you can drop your risk of dementia by 22 to 65%. There was a twin study where one twin had good oral health and the other had poor oral health. The one with poor oral health had much higher rates of dementia. Why is good oral health important? The biggest problem with aging is low-grade inflammation. If you have poor oral health, microbes seep through your gums and your body gets inflamed, contributing to dementia and Alzheimer's. Moral of the story: brush your teeth. Let's finish with practical stuff for those with kids. If microbes are important, how do we fix it? The trick is to think of a balance. We've come a long way in preventing kids from dying of infections. Hygiene works. But we've tipped the scales too far. Kids need to be exposed to the microbes they're used to getting. We've evolved with these things. It starts when the mother is pregnant. There are studies showing that the mother's microbes affect how the fetus develops. If you're a thin mother in the third trimester and you overeat, your microbes go towards obesity. When the kid is born, that kid inherits the mother's microbes and stands a much higher chance of being obese, even if the mother was thin to begin with. We talked about the first birthday present, the big gulp on the way out. The microbes the kid acquires break down breast milk. Vaginal microbes are beneficial, like probiotic bugs. If you have to have a C-section, you can do a vaginal swab. You swab the vagina, and when the kid is born, you smear the microbes all over the kid to inoculate them. The studies are not long enough to know if it works, but naturopaths are routinely doing this. Breastfeeding is better. We always thought it was because of mother's antibodies. Now we know that most of breast milk can't be broken down by our bodies. We rely on the microbes the kid acquired at birth to break it down. There are studies showing that there are actually microbes in breast milk that colonize the kid. Formula companies are scrambling to improve formula. Kids start growing up. Pacifiers. Parents use them. The kid spits it out, you put it back. It falls on the floor. You have two choices: wash it off in the bathroom or put it in your own mouth and then back in the kid's. If you put it in your own mouth, those kids have much less asthma, obesity, and allergies than if you wash it off. So saves a trip. Hand sanitizer. It kills 99.9% of germs. Chuck it. This is poison. The FDA has banned triclosan, the active ingredient, because there are no studies showing it works. Soap and water is all you need. When you use hand sanitizer, you kill off all the good microbes and increase the chance of bad ones colonizing. Kids get dirty. If dirt exposure was so bad, wouldn't we have evolved not to get dirty? Kids put everything in their mouths. My argument is they're trying to get microbes from the world. Get a dog. Dogs roll around in the dirt, find feces, get really dirty, then come bounding into the house and roll over the kid and lick them. If you have a dog and a young kid, you decrease the kid's chance of getting asthma by 20% and also decrease the chances of obesity. Cat lovers, sorry. Cats just sit in the corner. There's no data either way. How do you change your microbes? The easiest way is what you eat. You are what you eat. I argue your microbes are what you eat. We eat a lot of white flour and white sugar, processed foods. They are absorbed quickly in the upper intestine, long before they get to where the microbes are. Your mother was right. Eat your vegetables, nuts, legumes, high fiber. Not so much for the nutrients, but you're feeding the microbes. A healthy diet, decreasing red meat, feeds the microbes to allow them to do their thing. In an experiment we did, each color is different microbes in untreated mice and mice treated with two different antibiotics. Antibiotics drastically impact the microbes. The average kid in the US gets 10 to 12 courses of antibiotics by the time they get to school. Early in life, these microbes are bouncing around. If you have an antibiotic, you shift the kid's microbes. They come back a bit, but not the same. Then you hit them again, and it goes further. By 10 to 12 courses, these microbes are over here. Antibiotics cause resistance. We now know they're not harmless. You have to balance them. If the kid is dying of a bacterial infection, use antibiotics. But if the kid has a viral ear infection, antibiotics don't work. Wait 24 hours. The biggest crime in antibiotics in the US and Canada is that 80% of our antibiotic use is in agriculture because it gives a 15% increase in growth weight. It's banned in Europe. But it gives a 15% increase in growth in any animal. Studies show it works in humans too. Maybe the success of antibiotic use has influenced the obesity epidemic. Every generation, our society gets cleaner. Every generation, we have less diverse microbes to choose from. You cannot go back to the microbes your great-grandfather had. Unless they're alive and you ask for a sample. These are endangered species. We've evolved with these microbes. We're banning them like crazy. We can't go back. We need to rethink this. Finally, I have to put a plug in for vaccines. There's been a lot of misinformation. All the data shows vaccines work. The whole autism link was fraudulent and disproven. If you have kids, do the vaccines. There was a recent political appointment of a vaccine denier to reevaluate vaccines. That is going to cost a lot of kids' lives. The first Bush did the experiment when they banned the whooping cough vaccine. Lots of kids died because it came roaring back. Vaccines are a wonderful tool. This is a book I wrote with a co-author, Marie-Claire Arrieta. It's for sale back there. It takes us through all this. The science is behind it, but it's designed so anyone can read. The nice thing is we seem to have got the balance right. Pediatricians agree with it, and even naturopaths agree. It's full of helpful hints. There are chapters on asthma, obesity, diabetes, and many other diseases. I'll refer you to the website letthemeatdirt.com. If you're going to ask about probiotics, there's a link that takes you to clinical studies showing which probiotics work for what disease. A few work, but most don't. I'll stand around afterwards and maybe sell a few books. I want to leave you with a message. This is Seattle, like Vancouver. It rains a lot. We need to let kids be kids, experience their world, because they have to do that to pick up their microbes and be healthy. Thanks a lot.

That's the whole hygiene question. If you are at daycare and everyone has diarrhea, definitely wash the hands. This works for the hygiene concept, but for daily maintenance, the answer is no. It doesn't do at all. Use it in a hospital setting, for example, but we honestly don't need it here.

Absolutely. I'm going to call it probiotics 2.0. I co-founded a company in Boston that's doing exactly that. They're doing vaginal recolonization and thinking about screening for asthma risk. The thing about probiotics is that they're often from the vagina and you're putting them in the gut. They don't stick. There's a reason you have to take 10 billion a day because they just flush through. In the future, it'll be a pill containing 20 different microbes from the gut for the gut. We know these microbes have particular benefits, so we repopulate the whole ecological system. Probiotics of the future are very exciting. We're still early days on identifying which microbes give us particular benefits. This field is only about 7 to 10 years old, but I think we're going to see major change.

A lot of the similar concepts apply. Diet is a major thing. Asthma is early life immune system, so I haven't seen data that later in life you can affect asthma. But things like IBD, obesity, diabetes, there's neat stuff coming out. Even cancer chemotherapy. There are beautiful studies showing they can tell whether you respond to chemo depending on what microbes you have. I'm toying with writing a book on the other end of life as we age. Probiotics are not going to hurt. Diet and exercise are major components because both influence the microbes. Pay attention to the literature because it's coming fast, but filter out the quackery.

Yes. The hygiene hypothesis was discovered by realizing that younger siblings had less disease because older kids brought stuff home. There's no data that getting infections is good for kids. But when a kid hits daycare, you're going to have a year of colds. You can see shifts in their microbes. The question is, if you're a mother with a C-section kid, can't breastfeed, live on the 22nd floor of a condo with no pets, how are these kids going to get normal things? Generally, daycare is a good way of mixing up the microbes, except when infections rip through. We can tell in the feces whether the family has a dog based on dog microbes. The environment really does influence. There are studies that daycare enhances community exposure to microbes.

It's diet and exercise. Epidemiologists attribute it to a high-fat diet and lack of exercise in the southern areas of the US. I haven't seen data on hand sanitizer use. I think it's the whole environment these people are living in.

They're just coming out. Bariatric surgery really does affect the microbes because you're taking out pieces of the intestine. What that means in terms of health complications down the line, I think it's still early days. But there's no doubt you shift the microbes. Probiotics can't hurt. They seem to help digestion. For pouchitis, there's nice data that probiotics decrease it.

There are about a thousand species of microbes in your gut. Each person is different. There are about 300 in your mouth, about a hundred on the skin. There have been interesting studies on the microbes of people with little exposure to the outside world. Their microbes are very different, but their diet is very different too. One anthropologist gave himself a fecal transfer with that feces and got severe diarrhea. So that experiment didn't work. The idea is to biobank the good ones. Groups are working on that, trying to figure out which ones are important.

The title is a bit tongue in cheek. Let kids eat the microbes found in dirt. It'll never be a bestseller. If a kid picks up a handful of dirt today, it's much safer than a hundred years ago. I think it's safe. I as a kid would pull carrots out, scrape the dirt off, and chew on them. You're getting good microbial exposure. Let the kid play in the sandbox, unless there's cat feces. Lick the floor of your house, that's okay, but not the subway station. It's a balance. I've not seen studies of ramming dirt down a kid's mouth. The unwashed carrot variety is good. The Brazil story: Brazil was bright red for asthma. In Brazil, C-sections are about 80%, and in Rio de Janeiro, about 95%. Part of it is trendy, but also obstetricians are unionized and don't do night call. So if you want to deliver a kid, it has to be during daylight hours. It will be interesting to see what happens to all these C-section kids. There's a movement to convince obstetricians to do normal vaginal deliveries sometimes.

Yes. It's all the ones that grow in that picture. Plants, legumes, nuts, highly complex unprocessed foods. White sugar, white flour, processed meats are at the other end, driving obesity-type microbes. The work with DayTwo shows personalized diet. Generally, the old story is now backed by microbes. The Western diet is the worst diet for microbes. The better diets are plant- and legume-based. There's a book called The Blue Zones about areas where people live to 100. They have social contacts, exercise, eat little red meat, and a lot of legumes. Diet is going to see a major resurgence.

Most of the beneficial microbes are in the vagina, not on the skin. The studies on skin-to-skin are unclear. I haven't seen any evidence to support the tooth decay claim. About the age, around five years of age, it becomes less important. The bookends of life are 0 to 5 and 65 plus, when the microbes seem to have more effect. In middle life, it's things like diabetes and obesity. Early life is about setting up, and later life the immune system goes wonky. You still have time with your 13-month-old.