Читать книгу Let Them Eat Dirt - B. Brett Finlay - Страница 10
Оглавление1:Children Are Microbe Magnets
Microbes: Kill Them All!
Microbes are the smallest forms of life on Earth. They encompass bacteria, viruses, protozoa, and other types of organisms that can be seen only with a microscope. Microbes are also the oldest and most successful forms of life on our planet, having evolved long before plants and animals (plants and animals actually evolved from bacteria). Although invisible to the naked eye, they play a major role in life on Earth. There are an astounding 5 x 1030 (that’s 5 followed by 30 zeroes!) bacteria on Earth (for comparison, there are “only” 7 x 1021 stars in the universe). Collectively, these microbes weigh more than all the plants and animals on the entire planet combined. They can live in the harshest and most inhospitable environments, from the Dry Valleys of Antarctica to the boiling hydrothermal vents on the seafloor—they can even thrive in radioactive waste. Every form of life on Earth is covered in microbes in a complex yet usually harmonious relationship, making germophobia the most futile of phobias. Unless you live in a sterile bubble without any contact with the outside world (which is a time-limited proposition; see Bubble Boy, page 15), there is no escaping microbial life—we live in a world coated in a veneer of microbes. For every single human cell in our bodies, there are ten bacterial cells inhabiting us; for every gene in our cells, there are one-hundred fifty bacterial genes, begging the question: Do they inhabit us or is it really the other way around?
While in its mother’s womb a baby is for the most part sterile, but at the moment of birth it receives a big load of microbes, mainly from its mother—a precious first birthday gift! Within seconds, the baby is covered in microbes from the very first surfaces it touches. Babies born vaginally encounter vaginal and fecal microbes, whereas babies born via C-section pick up microbes from the maternal skin instead. Similarly, babies born at home are exposed to very different microbes than if they are born in hospitals, and different homes (and hospitals) have different microbes present.
Why does all this matter? Well, until very recently hardly anyone thought it did. Until recently, whenever we thought of microbes—especially around babies—we considered them only as potential threats and were concerned with getting rid of them, and it’s no surprise why. In the past century, we have experienced the benefits of medical advances that have reduced the number and the degree of infections we suffer throughout life. These advances include antibiotics, antivirals, vaccinations, chlorinated water, pasteurization, sterilization, pathogen-free food, and even good old-fashioned handwashing. The quest of the past hundred years has been to get rid of microbes—the saying was “the only good microbe is a dead one.”
This strategy served us remarkably well; nowadays, dying from a microbial infection is a very rare event in developed countries, whereas only a hundred years ago, seventy-five million people died worldwide over a span of two years from the H1N1 influenza virus, also known as the Spanish flu. We have become so efficient at avoiding infections that the appearance of a dangerous strain of Escherichia coli (aka E. coli) in a beef shipment or Listeria monocytogenes in spinach leads to massive recalls and exportation bans, along with accompanying media hysteria. Microbes scare all of us, and rightly so since some of them are truly dangerous. As a result, with very few controlled exceptions such as yogurt or beer, we often think that the presence of microbes in something renders it undesirable for human use. The word antimicrobial is a sales feature in soaps, skin lotions, cleaning supplies, food preservatives, plastics, and even fabrics. However, only about one hundred species of microbes are known to actually cause diseases in humans; the vast majority of the thousands of species that inhabit us do not cause any problems, and, in fact, seem to come with serious benefits.
At first glance, our war on microbes, along with other medical advances, has truly paid off. In 1915 the average life span in the US was fifty-two years, about thirty years shorter than it is today. For better or for worse, there are almost four times more humans on this planet than there were just a hundred years ago, which translates to an incredibly accelerated growth in our historic timeline. Evolutionarily speaking, we’ve hit the jackpot. But at what price?
Revenge of the Microbes
The prevalence of infectious diseases declined sharply after the emergence of antibiotics, vaccines, and sterilization techniques. However, there has been an explosion in the prevalence of chronic non-infectious diseases and disorders in developed countries. One hears about these in the news all the time since they’re very common in industrialized nations, where alterations to our immune system play an important role in their development. They include diabetes, allergies, asthma, inflammatory bowel diseases (IBDs), autoimmune diseases, autism, certain types of cancer, and even obesity. The incidence of some of these disorders is doubling every ten years, and they are starting to appear sooner in life, often in childhood. They are our new epidemics, our modern-day bubonic plague. (By contrast, these diseases have remained at much lower levels in developing countries, where infectious diseases and early childhood mortality are still the major problems.) Most of us know someone suffering from at least one of these chronic illnesses; due to this prevalence, researchers have focused their attention on identifying the factors that cause them. What we know now is that although all of these diseases have a genetic component to them, their increased pervasiveness cannot be explained by genetics alone. Our genes simply have not changed that much in just two generations—but our environment sure has.
About twenty-five years ago a short scientific article published by an epidemiologist from London attracted a lot of attention. Dr. David Strachan proposed that a lack of exposure to bacteria and parasites, specifically during childhood, may be the cause of the rapid increase in allergy cases, since it prevents proper development of the immune system. This concept was later termed the “hygiene hypothesis,” and an increasing number of studies have explored whether the development of many diseases, not just allergies, can be explained by this hypothesis. There is now a large amount of very solid evidence, which we’ll examine in the following chapters, supporting Dr. Strachan’s proposal as generally correct. What remains less clear is what exact factors are responsible for this lack of microbial exposure. For his study on allergies, Dr. Strachan concluded that “declining family size, improvements in household amenities, and higher standards of personal cleanliness” contributed to this reduced contact with microbes. While this may be true, there are many other modern-life changes that have an even stronger impact on our exposure to microbes.
One of these changes can be attributed to the use, overuse, and abuse of antibiotics—chemicals that are designed to indiscriminately kill bacterial microbes. Definitely one of, if not the greatest discovery of the twentieth century, the emergence of antibiotics marked a watershed before-and-after moment in modern medicine. Prior to the advent of antibiotics, 90 percent of children would die if they contracted bacterial meningitis; now most cases fully recover, if treated early. Back then, a simple ear infection could spread to the brain, causing extensive damage or even death, and most modern surgeries would not even be possible to contemplate. The use of antibiotics, however, has become far too commonplace. Between the years 2000 and 2010 alone there was a 36 percent increase in the use of antibiotics worldwide, a phenomenon that appears to follow the economic growth trajectory in countries such as Russia, Brazil, India, and China. One troubling thing about these numbers is that the use of antibiotics peaks during influenza virus infections, even though they are not effective against viral infections (they are designed to kill bacteria, not viruses).
Antibiotics are also widely used as growth supplements in agriculture. Giving cattle, pigs, and other livestock low doses of antibiotics causes significant weight gain in the animals and, subsequently, an increase in the meat yield per animal. This practice is now banned in Europe, but is still legal in North America. It seems that antibiotic overuse in humans, especially in children, is inadvertently mimicking what occurs in farm animals: increased weight gain. A recent study of 65,000 children in the US showed that more than 70 percent of them had received antibiotics by age two, and that those children averaged eleven courses of antibiotics by age five. Disturbingly, children who received four or more courses of antibiotics in their first two years were at a 10 percent higher risk of becoming obese. In a separate study, epidemiologists from the Centers for Disease Control and Prevention (CDC) found that states in the US with higher rates of antibiotics use also have higher rates of obesity.
While these studies didn’t prove that antibiotics directly cause obesity, the consistency in these correlations, as well as those observed in livestock, prompted scientists to have a closer look. What they found was astonishing. A simple transfer of intestinal bacteria from obese mice into sterile (“germ-free”) mice made these mice obese, too! We’ve heard before that many factors lead to obesity: genetics, high-fat diets, high-carb diets, lack of exercise, etc. But bacteria—really? This raised skepticism among even the biggest fanatics in microbiology, those of us who tend to think that bacteria are the center of our world. However, these types of experiments have been repeated in several different ways and the evidence is very convincing: the presence and absence of certain bacteria early in life helps determine your weight later in life. Even more troubling is the additional research that shows that altering the bacterial communities that inhabit our bodies affects not just weight gain and obesity, but many other chronic diseases in which we previously had no clue that microbes might play a role.
Let’s take asthma and allergies as an example. We are all witnesses to the rapid increase in the number of children suffering from these two related diseases. Just a generation ago it was rather unusual to see children with asthma inhalers in schools. Nowadays, 13 percent of Canadian children, 10 percent of US children, and 21 percent of Australian children suffer from asthma. Peanut allergies? That used to be incredibly rare, but is now so frequent and so serious that it has led to peanut-free schools and airplanes. As with the obesity research, it is now evident that receiving antibiotics during childhood is associated with an increased risk of asthma and allergies.
Our laboratory at the University of British Columbia became very interested in this concept and decided to do a simple experiment. As had been observed with humans, giving antibiotics to baby mice made them more susceptible to asthma, but what we observed next left us in awe. If the same antibiotics were given when the mice were weaned and no longer in the care of their mothers, there was no effect in susceptibility to asthma. There appeared to be a critical window of time, early in life, during which antibiotics had an effect on the development of asthma. When given orally, the antibiotic that we chose, vancomycin, kills only intestinal bacteria, and does not get absorbed into the blood, lungs, or other organs. This finding implied that the antibiotic-driven change in the intestinal bacteria caused the increase in the severity of asthma, a disease of the lungs! This experiment, as well as others from several different labs, came to the same conclusion: modifying the microbes that live within us at the beginning of our life can have drastic and detrimental health effects later in life. The discovery that this early period in life is so vulnerable and so important tells us that it’s crucial to identify the environmental factors that are disturbing the microbial communities that inhabit us during childhood.
One of these factors has been observed by comparing children raised on rural farms to those raised in a city. Several studies have shown that exposure to a farming environment makes children less likely to develop asthma, even children from families with a history of asthma, and scientists are now beginning to learn why. Farm-raised children are exposed to more animals, more time outside, and a lot more dirt (and feces!), all things that are known to stimulate the immune system. A critical part of the training and development of the immune system occurs in the first years of life. Asthma, characterized by a hyperactive immune system, seems to have a higher chance of developing in a child with a limited exposure to these immune stimulants, because without them, the immune system does not have all the tools for proper development. By cleaning up our children’s environments, we prevent their immune systems from maturing in the way they have for millions of years before us: with lots and lots of microbes. Life for our ancestors involved massive exposure to microbes from the environment, food, water, feces, and many other diverse sources. Compare that to our current way of life, where meat comes on sterile Styrofoam pans wrapped in plastic wrap, and our water is treated and processed until it’s free of nearly all microbes.
Kids Will Be Kids
A friend, Julia, moved to a small free-range pig and poultry farm when her first child was a preschooler. She observed firsthand how differently a kid grows up in a city and on a farm. She has always been outdoorsy, so even when she was living in the city she would let Jedd, her oldest child, play outside a lot. They would go to parks and playgrounds, where she would encourage Jedd to get dirty, play in sandboxes and mud puddles—she even allowed him to put (safe-sized) objects in his mouth, like big rocks or leaves. Her outdoorsy nature, she thought, would make their transition to rural life easier, and it did in many ways. But nothing prepared her for the things she’s seen her kids do on their farm. When her second baby was born, she would strap him on her back every morning so she could go to their chicken coop to pick up eggs. Jedd, timid with the animals at first, was now chasing and riding the chickens, tasting their feed and touching the fresh eggs. A couple of times she even caught him chewing on something he had picked up from the ground. Anyone who has stepped inside a chicken coop knows what’s on the floor, so she’s pretty sure Jedd has tasted chicken droppings at least a few times. Clearly, Julia freaked out at first, but it’s hard to prevent a five-year-old boy from getting dirty when you’re busy working and looking after a second child. After realizing that Jedd wasn’t getting sick from his newly acquired tastes of the farm, Julia relaxed a bit. Jedd, now eight years old, is responsible for gathering the eggs every morning. Newly laid eggs are often soiled and he doesn’t wear gloves. He washes his hands when he’s done, but it’s impossible that some of that stuff hasn’t made it into his mouth.
Julia’s second child, Jacob, was born and raised on the farm and, like his big brother, he was never the slightest bit hesitant to get dirty. He was once found playing knee-deep in a cesspool of pig waste. At fourteen months he swallowed a handful of fresh chicken droppings as Julia rushed towards him to prevent it. Her initial worry that her children were going to contract a disease from all this messiness dissipated as her kids remained healthy.
Nowadays, with her third baby strapped on her back, she doesn’t even flinch at the sight of the two older boys doing what all farm kids do: getting very, very dirty. Every single day, they come home with dirt, poop, feathers, and who knows what else caked onto their skin and clothes. They try their best to keep their farm boots for outdoor use only, but it inevitably happens that dirty boots make it onto the living room carpet. Julia makes sure to wash their hands before they eat and they rarely miss a daily bath (the color of the bathwater is a constant reminder of why daily baths are mandatory in their house).
Even if they play outside a lot, most children growing up in urban environments rarely ever reach the level of dirtiness that Julia’s kids experience on a daily basis. From this perspective, a farm kid (and his microbes) is very different from a city kid. We are by no means suggesting that we should all allow our kids to play with animal waste, as they could become sick from this. But farms in general provide a microbe-rich environment that has proven beneficial for the development of the immune system, and that really is akin to the way we used to live, which has been seriously altered only in the past few generations.
The vast majority of children have something in common with Jedd and Jacob, in that they all seek out dirt and enjoy getting messy and sucking on things. Why is that? Our natural behavior in the early years of life definitely tries to maximize our exposure to microbes: babies are in direct contact with maternal skin while breastfeeding, they are constantly putting their hands, feet, and every imaginable object in their mouths. Crawlers and early walkers have their hands all over the floor, and then in their mouths. It often seems that they’re waiting for the few seconds that parents take their eyes off them to almost magically find and put the dirtiest thing they can reach in their drool-dripping mouths. It makes us wonder: Are kids instinctually drawn to microbes?
Older kids love digging in the dirt, picking up worms, rolling on the ground, catching frogs and snakes, etc. Perhaps this is actually natural behavior designed to populate kids with even more microbes. Children rarely hesitate to lick anything or anyone. As would be expected, children also suffer more infections than adults. Their vacuum-like behavior ensures that they taste the microbial world and subsequently train their immune system to react to it accordingly. If they encounter a disease-causing microbe, also known as a pathogen, their immune system detects it, reacts to it in the form of sickness, and then tries hard to remember it so that their body can prevent it from causing disease the next time this pathogen makes a visit. When the immune system encounters a harmless microbe—and the vast majority of microbes are harmless—it detects it and, through a series of mechanisms that science does not yet fully understand, decides to ignore or tolerate it. Thus, if children’s lifestyles and behaviors dictate a limited exposure to these training events, their immune system will be partially immature and will not learn how to properly react to a pathogen or how to tolerate harmless microbes. The consequence of missing out on this early training appears to be that, later in life, the immune system may react too fiercely to these harmless microbes, which could trigger inflammatory responses in various organs of the body. This contributes to the appearance of “developed country diseases” (like asthma and obesity) that are becoming so prevalent today.
Microbes to the Rescue
Helping develop our immune systems is only part of what microbes do for us. They are in charge of digesting most of our food, including fiber and complex proteins, and chopping them into more digestible forms. They also supply the essential vitamins B and K by synthetizing them from scratch, something our own metabolism cannot do. Without the vitamin K from microbes, for example, our blood would not coagulate.
Good bacteria and other beneficial microbes also help us combat disease-causing microbes. Experiments in our lab have shown that infections from Salmonella, a diarrhea-causing bacterium, are far worse when antibiotics are given before the infection actually occurs. Similarly, many of us have experienced the side effects of a long bout of antibiotics: abdominal cramps and watery diarrhea. The microbes we harbor live in a balanced state that provides us with so many benefits, all in exchange for a portion of our daily calories and a warm, dark place to live with regular feeding and watering.
But changes in our modern lifestyles are altering this balance, especially during a critical window in early life. In many developed countries, about 30 percent of babies are born by cesarean section, antibiotic usage is a lot more frequent, and most children do not suffer serious infections thanks to vaccines. Far from suggesting that any of these things should be avoided, our aim is to educate parents, as well as parents-to-be, grandparents, and caregivers, about the potentially life-changing decisions we make on a daily basis by raising children in an environment that’s much cleaner than ever before. As parents ourselves, we understand that most of us do the best we can with what we have, and it is not our intention to dictate how other people should raise their children. However, as microbiologists, we are becoming increasingly aware of the key role our resident microbes have in shaping our bodies’ development. The microbial communities of babies and young children are being altered in ways that may make them sicker later in life, by the very same practices intended to keep them healthy. Talk about a double-edged sword!
The scientific community is just beginning to grasp this new knowledge, and the general public is just starting to hear about it in news articles of (often misinterpreted) studies. Preventing serious illnesses should always be one of our biggest concerns, but we can also do a great deal to try to distinguish between a necessary intervention, such as giving an antibiotic to fight a life-threatening bacterial infection, and an unnecessary and hyperhygienic practice, such as applying antimicrobial hand sanitizers every time a child plays outside. Not all children will or should be raised like Jedd or Jacob, but we can certainly change those unneeded aspects of our far-too-clean world.
In our classical training as microbiologists, we studied only the microbes that cause diseases and the ways to kill them. Now we acknowledge that we have, for many years, ignored the vast majority of microbes that keep us healthy. Our research labs are changing focus, and we are beginning to think it’s time for everyone to become better hosts to our microbial guests.
BUBBLE BOY
David Vetter was born in 1971 in Houston, Texas, with a rare genetic disorder that left him without a working immune system. Any contact with a nonsterile world would mean certain death. Because of this, he was delivered by C-section and placed in a sterile bubble immediately after his birth. In a controversial medical decision, he lived in the hospital in a bubble that grew with him. His medical treatment included many courses of antibiotics to prevent any bacterial infection. Being devoid of bacteria meant that doctors also had to feed him a special diet, along with the essential vitamins K and B, which are normally produced by intestinal bacteria. David’s story reflects the impossibility of living without an immune system in a world full of microbes, as well as a human’s dependence on microbes and what they produce for us. Sadly, David died at the age of twelve from a viral infection a few months after a bone marrow transplant was finally performed.
