These highlights are from the Kindle version of Follow Your Gut by Rob Knight and Brendan Buhler.
Thanks to new technologies, many of them developed only within the past few years, scientists today know more about the microscopic life-forms inside us than ever before. And what we’re learning astonishes. These single-celled organisms—microbes—are not only more numerous than we thought, inhabiting in enormous numbers almost every nook and cranny of the body, but they’re also more important than we ever imagined, playing a role in nearly all aspects of our health, even in our personality.
You are made up of about ten trillion human cells—but there are about a hundred trillion microbial cells in and on your body.
Different sets of species inhabit different parts of the body, where they play specialized roles. The microbes that live in your mouth are distinct from those residing on your skin or in your gut. We are not individuals; we are ecosystems.
In 1977, American microbiologists Carl Woese and George E. Fox mapped the tree of life by comparing life-forms at the cellular level, using ribosomal RNA, a relative of DNA that’s housed in every cell and used in making proteins. The result was startling. Woese and Fox revealed that single-celled organisms are more diverse than all of the plants and animals combined.
Now, through a process called next-generation sequencing, we can collect cell samples from different parts of the body, rapidly analyze the microbial DNA they contain, and combine information from samples across the body to identify the thousands of species of microbes that call us home. We’re finding bacteria, archaea, yeasts, and other single-celled organisms (such as eukaryotes) that collectively have genomes—the genetic recipes that define them—longer than our own.
About a decade ago, if you wanted to know what made up your microbiome, you’d need $100 million. Now obtaining that same information costs about $100—so cheap that it might soon become a routine medical procedure ordered by your doctor.
If we’re going by weight, the average adult is carrying about three pounds of microbes. This makes your microbiome one of the largest organs in your body—roughly the weight of your brain and a little lighter than your liver.
We’ve already learned that, in terms of sheer numbers of cells, the microbial cells in our bodies outnumber the human cells by up to ten to one. What happens if we measure by DNA? In that case, each of us of us has about twenty thousand human genes. But we’re carrying some two million to twenty million microbial genes. Which means that, genetically speaking, we’re at least 99 percent microbe.
Why is it that, when we are disarmed of our soaps, antiperspirants, powders, and perfumes, we stink so? Largely because of microbes that feast on our secretions and make them yet smellier.
As noted earlier, mosquitoes do prefer the smell of some individuals over others, and microbes are responsible. These microbes metabolize the chemicals our skin produces into different volatile organic compounds that the mosquitoes like or dislike. Different species of mosquitoes favor different parts of our bodies.
The microbes on your hands are very distinct from other people’s—on average, at least 85 percent different in terms of species diversity—which means that you have a microbial fingerprint.
Our environments greatly influence the types of microbes that gather in our noses. And children who have more diverse kinds of bacteria in their nose early on, such as those who live on or near farms, are less likely to develop asthma and allergies later in life. It turns out that playing in the dirt can be good for you.
Next, we come to the intestines. We believe this to be the largest and most important microbial community in the body. If you’re a microbe living on a human, this is the main act. Here is the great mansion of our gut, some twenty to thirty feet long and full of nooks and crannies. It’s good living for microbes: warm, plenty to eat, plenty to drink, and a convenient sewer system.
Your first microbes probably come during birth. You gain them while passing through your mother’s birth canal, which is lined with vaginal bacteria. Although different women can have rather different vaginal microbial communities, during pregnancy their microbial communities all move into the same state.
Children who have more diverse microbial communities as youngsters—those exposed to a range of influences such as siblings, pets, or living on or near a farm—tend to have lower rates of immune system defects, such as hay fever, than children who grew up in cities do.
Some people are born with resistance to certain diseases. You’ve probably heard of Typhoid Mary, a New York cook in the early twentieth century who carried the bacteria that causes the disease typhoid fever. She infected family after family with her excellent cooking, which was laced with a dose of her not-so-excellent microbes. But Mary was never sick. She was naturally immune to the fever she carried inside her. Where does such resistance come from?
Interestingly, simply living in a setting with more diverse microbes (say, a home with a backyard garden rather than an urban apartment far from any parks) seems to decrease risk of allergic disease.
In general, exposure to diverse microbes, whether through older siblings, pets, or livestock—or through good old-fashioned playing outdoors—seems to help, even if scientists are still sorting out the specific microbes involved. It may be that diversity itself is most important.
From their throne in our guts, microbes not only influence how we digest food, absorb drugs, and produce hormones, but they can also interact with our immune systems to affect our brains. Together the various interactions between microbes and the brain are called the microbiome-gut-brain axis, and understanding this axis could have profound implications for our understanding of psychiatric disorders and our nervous system.
The ability of soil microbes such as Mycobacterium vaccae to modulate the human immune system has long been known, leading some researchers to suggest that it might be possible to use them to vaccinate against stress and depression. In particular, Graham Rook at University College London has proposed that not having enough contact with our “old friends”—soil microbes that humans had been exposed to throughout human history but that we now isolate ourselves from by clean living—could explain the rapidly increasing frequency of diseases involving inflammation, such as diabetes, arthritis, and even depression.
Pettersson saw higher anxiety among germ-free mice—those raised in a bubble without any microbes of their own—than among normal mice. But if he transferred the normal bacteria to mice early on, within a few days of birth, they grew up to behave the same way that normal mice did. In contrast, if they were colonized only weeks afterward, they behaved anxiously, like germ-free mice. Here we see that, at least in mice, microbes act in early childhood to alter behavior irreversibly.
Specific probiotics have also been shown to alter behavior, both in mice and in humans. There are now more than five hundred studies linking probiotics to behavior, especially anxiety and depression. For example, the probiotic Lactobacillus helveticus can decrease anxiety in mice,10 and Lactobacillus reuteri can reduce the likelihood that mice will develop infections when they’re stressed. Lactobacillus rhamnosus GG has been reported to reduce obsessive-compulsive behaviors, such as marble burying, in mice, and as we mentioned in the section on autism, probiotic strains of Bacteroides fragilis can rescue mice from some autistic-like traits, including cognitive deficits and repetitive behavior.
In 1859 Pasteur showed that sterile nutrient broth in a sealed flask couldn’t spontaneously generate life; growth occurred only if the flask was broken, exposing the broth to microorganisms in the air—an experiment that gave us the germ theory of disease.
In 1865, after reading Pasteur’s work, a British surgeon named Joseph Lister developed antiseptic methods that increased dramatically the likelihood of his patients’ survival—techniques that, together with antibiotics, essentially make modern surgery possible.
You may not have heard of them, but prebiotics are like fertilizer for your microbes, providing nutrients they need and that favor the beneficial species. Prebiotics are mostly soluble fibers such as fructans (for example, inulin, lactulose, and the tasty-sounding galacto-oligosaccharides), which naturally occur in some fruits and vegetables.
There have been a few randomized, controlled clinical trials (the kind of study that produces the most reliable results) of prebiotics that showed some benefit for Crohn’s disease, constipation, and insulin resistance, but most clinical trials to date are still at the stage of proving safety, and the numbers of participants are often too small to draw reliable conclusions about what you should do.
Probiotics are mostly bacteria found naturally in the human gut, or in fermented foods such as yogurt. Examples include various species of Bifidobacterium and Lactobacillus. Probiotics are defined as live microorganisms that, when administered in sufficient quantity, benefit health.
The US Food and Drug Administration (FDA) has not yet approved any health claim for probiotic products, so they are marketed as food supplements. (Buyer beware!)
It’s also unclear whether or not the preparation you can buy at the supermarket contains any live organisms after being shipped there and sitting on the shelf; microorganisms require very specific conditions to survive.
People with severe gastrointestinal illness can literally crap themselves to death. One such disease is Clostridium difficile–associated diarrhea. People with C. diff have to go to the bathroom dozens of times a day, and the disease is often life threatening. It’s also one of the most prevalent hospital-acquired infections in the United States, where each year it sickens 337,000 people and kills 14,000 of them.
Many people take antibiotics for C. diff, but this therapy often fails. A complement or possibly an alternative to antibiotic treatment is instead to give the patient microbes from someone who’s healthy. One radical and experimental C. diff treatment is called fecal transplantation. It’s exactly what it sounds like: a healthy volunteer, usually a relative, donates a stool sample, which is then diluted and given to the patient. There are two ways to transplant the feces: the northern route and the southern route. Both routes are effective, curing 90 percent of C. diff patients.
So far vaccines have been used primarily for individual pathogens, starting with the nastiest ones, for obvious reasons. But as the list of vaccines expands, less-lethal kinds of microbes are being targeted, including bacteria and viruses that might kill you decades after they infect you (such as human papillomavirus, or HPV, a known cause of cervical cancer) rather than immediately.
According to the World Health Organization, depression is now the leading cause of disability in the United States and is rapidly becoming more common in the developing world. This increase in depression rates matches the rise of other diseases frequently considered to be Western, such as inflammatory bowel disease, multiple sclerosis, and diabetes, all of which, we now know, have both immune and microbial components. Could our estranged soil bacteria, which modulate the immune system, be playing a role? In experiments in mice, Mycobacterium vaccae, a soil bacterium, has reduced anxiety.
Right before Amanda underwent an unplanned cesarean, she was given antibiotics. And minutes after our daughter’s birth, doctors put antibiotic drops in her eyes. No one asked—they just did it. This is a standard treatment designed to guard against the sexually transmitted disease gonorrhea, which can cause conjunctivitis in infants.
While vaccines continue to be at least 90 percent effective for many diseases, antibiotics are becoming less effective, in part because of their misuse and overuse, which is responsible for the rapid spread of antibiotic resistance, as Marty Blaser, a medical microbiologist at New York University, has outlined so eloquently in his book on the topic, Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues. (A sobering fact: more than 70 percent of the bacteria that cause infections in US hospitals are resistant to at least one of the antibiotics normally used to treat them.)
Blaser argues—and many agree—that antibiotics are the equivalent of the chemical weapon napalm. They damage a great many organisms within us, depleting our microbial heritage in ways we’re only beginning to understand, with grave ramifications for health and society.
Livestock in the United States is commonly treated with low doses of antibiotics solely to increase the size, and thus the value, of the animals. This is the worst-case scenario for antibiotic resistance. While high doses of antibiotics kill (almost) everything, low doses allow changes that make a bug just a little more resistant, so that when the time comes that a particular bug is indeed life threatening, we’ve provided it with all the tools and skills it needs to sidestep our attempts to defeat it. Moreover, these bugs survive and spread throughout the agricultural industry and can jump species and infect humans. That’s why in 2006 the European Union banned low-dose antibiotic treatment for fattening livestock.
Blaser and his colleagues studied whether mice treated with low doses of antibiotics became heavier than normal mice. Indeed they did, showing that antibiotics affected mice as well as livestock. They also tested whether repeated high doses of antibiotics, like you might use on your kids when they have an ear infection, produced weight gain in mice. Again the answer was yes. In a second branch of the study, Blaser collaborated with epidemiologists—those who study trends in the health of whole populations, not just individuals—to ask whether people who had received antibiotics early in life later put on more pounds than those who didn’t. Once again the answer was yes: antibiotics in the first six months were associated especially with increased weight gain.
And early use of antibiotics could have something to do with the rocketing rates of food allergies among American children.
Ironically, one of the biggest problems with antibiotics is that they often make you feel better almost immediately. This might be why they’re so much more accepted by the public than a vaccine.
Antibiotics can have insidious long-term effects: they become less effective each time you take them and breed antibiotic-resistant bacteria strains that endanger the population as a whole. Plus, broad-spectrum antibiotics such as amoxicillin and ciprofloxacin, which target wide swaths of species, damage our entire microbiome and not just the pathogens we’re trying to cure.
If you have a bacterial infection, figuring out whether it’s a mild or deadly strain, and if it resists antibiotics, requires laboratory tests using culturing, antibodies, and DNA analysis that can take several days. By then it might be too late. Newer, faster technologies such as mass spectrometry (essentially zapping the sample with a laser and using very accurate scales at the molecular level to weigh the molecules) and better DNA sequencing may accelerate the process and ultimately save lives.
To begin building this system, hundreds of scientists are involved in the Human Microbiome Project, the Earth Microbiome Project, and American Gut, along with literally thousands of members of the general public who have provided both samples (of their feces) and support.
The research to come will ultimately yield not just detailed microbial maps of humanity but also a kind of microbial GPS—a guiding body of knowledge that will tell us where we are, as well as where we want to go and how to get there.
The Science (and Art) of Microbiome Mapping If what you hear about the microbiome can seem qualified or contradictory, it’s because this isn’t exactly rocket science—I’d submit it’s much harder. One of our biggest challenges is just figuring out what we’re looking at. In terms of DNA, humans are essentially identical. But at the microbial level, our similarities diverge quickly. The same body part on two people will often harbor very different microbial species (and even when we share species, their total populations may vary widely).
Choose two people at random and examine a single microbial cell from the first person’s stool, and then the second person’s. Only about 10 percent of the time will you find a cell of the same species in both people’s stool. In contrast, if you picked a position on the human genome from those same two people, their DNA would match 99.9 percent of the time. Not only is our microbial genome much more diverse than our human genome, the actual types of microbes differ vastly from person to person as well.
It gets more complicated when we begin to define what actually constitutes a unique microbial species. For animals, it’s relatively easy: if two animals can interbreed and produce offspring who are themselves fertile, they are, by definition, from the same species. But microbes don’t usually have sex. And when they do, they can exchange genetic material outside their species—so wildly outside it that, for example, bacteria have been shown to exchange with other bacteria, archaea, and even eukaryotes and viruses.