Let Them Eat Dirt. B. Brett Finlay
is packed with them.
About 500–1,500 species of bacteria live in the human gut; the types and numbers vary according to the different sections of the gastrointestinal system. Starting from the top down, the mouth harbors a diverse and complex microbiota—the tongue, cheeks, palate, and teeth are all covered in a dense layer of bacteria known as a biofilm. For example, the dental plaque that dentists remove from our mouths is one of these biofilms. The stomach, on the other hand, is not the best place for microbes, as it is as acidic as battery acid. Still, a few bacterial species have adapted to live under such conditions. Farther down are the small and large intestines, where the number of microbes continues to increase until we reach the very end of the large intestine. Oxygen follows the opposite pattern, as it gradually decreases towards the lower portions of the gut, allowing strict anaerobes (those that die when exposed to the slightest bit of oxygen) to flourish in the large intestine. The differences in living conditions within the small and large intestines determine the number and the types of bacteria that reside in each portion of the gut. For example, the slightly acidic and oxygenated environment in the upper small intestine allows for bacteria that are tolerant to these conditions, such as the bacteria we often eat in our yogurt, known as Lactobacilli. Unlike the upper small intestine, the large intestine, also known as the colon, moves or churns its contents very slowly and produces a lot of mucus, allowing for many more bacteria to grow, especially those that use mucus for food.
Another characteristic of the human microbiota is its variability between individuals. Although about one-third of bacterial species are shared between all humans, the rest of them are more specific, making our microbiome unique like a fingerprint. Similarities in microbiota are highly dependent on diet and lifestyle, and to a lesser extent, on our genes. For example, identical twins (who share all of their genes) can have very different microbiotas if one is a vegetarian and the other eats meat. Family members, including husbands and wives who are not genetically related, tend to have similar microbiotas due to a shared living environment and diet. Humans also have striking similarities with the microbiotas of several species of apes, but only those that are omnivores like us. Mountain gorillas, for example, have a microbiota much more closely related to pandas, because they both spend their days leisurely eating bamboo.
Once established in our intestine, microbial communities are very stable. Only drastic changes, such as adopting a vegan lifestyle or moving to a completely different part of the world, will significantly alter your microbiota. Going on antibiotics for a week to treat an infection will also affect your microbiota, but only temporarily in most cases. It will generally bounce back to something resembling its pre-antibiotic state after you finish the treatment and go about your old way of eating. However—and this is a big however—the microbiota takes about 3–5 years from the time we’re born to become a fully established community, and during this period it’s very unstable, especially during the first few months of life. Any drastic changes to it have a very high chance of altering the microbiota permanently. In fact, it is the early colonizers of the intestinal microbiota that have a major influence on the type of microbiome we have later in life. Thus, a short-lived event like a C-section may have long-lasting consequences, since a baby born this way starts with a very different microbiota than a baby born vaginally. The potential health outcomes and impact of this type of event during early life has major implications for later health and disease, as discussed in later chapters.
Immune Cell School
Given the strong associations between early-life alterations to the microbiota and immune diseases later in life, we might ask: What exactly are microbes doing to us when we’re babies that is so important? As mentioned in the previous chapter, microbes help us use food that we can’t digest properly, and they also fight off bacteria capable of causing us harm. We’ve known about these roles for decades, but they are just the tip of the iceberg. As soon as we’re born and begin getting colonized with bacteria, bacteria kick-start a series of fundamental biological processes in our body. One of them is the maturation of the immune system, the network of cells and organs that defend us from diseases.
Before scientists started unraveling the role of the microbiota in immunity, every doctor and scientist was taught that we’re born with an immature immune system that gets trained in a small organ called the thymus. Here, immune cells known as T cells—the strategists of our immune system—are taught who is a friend and who is a foe. This training boot camp lasts for a few years only, until the thymus disappears, and all our immune cells have acquired this knowledge. Immunologists deciphered a complex series of mechanisms showing exactly how this occurs, but they couldn’t explain one big question: How does the thymus teach immune cells which kinds of bacteria are beneficial and which ones aren’t? After all, since we’re covered head to toe (also inside and out) with microbes, mostly good ones, how do immune cells know the difference? The thymus does not interact with bacteria, so where could it get this information? It turns out this very important aspect of the training doesn’t occur in the thymus—it happens in our gut.
Before we’re born, the lining of our gut is full of immature immune cells, and as soon as we come into the world and bacteria start moving into their new home, these immune cells “wake up” almost magically. They start multiplying, they change the type of activities they do, and they even move to other parts of the body to train other cells with the information they just received. Experiments with germ-free mice, which are mice that are born into and kept in a completely microbe-free environment, show that without microbes the immune system remains immature, sloppy, and unable to fight off diseases properly.
Scientists haven’t figured out exactly how microbes do this at the molecular level, but it is known that most bacteria will teach these immune cells to tolerate them, whereas some bacteria—the pathogens that cause disease—have the opposite effect. This makes sense; if our immune cells started fighting off all bacteria indiscriminately, there would be an out-of-proportion inflammatory battle between the small quantity of immune cells and the vast numbers of bacteria right after we’re born. In reality it’s quite the opposite; despite the enormous amount of bacteria living in the intestine, it’s a relatively controlled and harmonious place. The way this is achieved is by the microbiota modulating the immune system, allowing most microbes to be tolerated.
Many inflammatory diseases, such as asthma, allergies, and IBD, are characterized by an overreactive immune response. Knowing what we do now about the importance of microbiota in immune system development, it’s not surprising that these diseases are being diagnosed in more and more children. They are, to a great extent, a consequence of the modern lifestyle changes that are altering the types of microbes that affect the immune system. There’s a reason immune cells wait for microbes to come and train them right after we’re born: because this is the way it has happened for millions of years and is the way it will always be. We need to find ways to modify our modern behavior so that immune cell school can function properly.
Feeding Our Microbes So They Can Feed Us
Another fundamental function of microbes is to aid in the regulation of our metabolism. Humans, just like any other living animal, obtain energy from food that is digested and absorbed in the intestines. Besides helping us digest certain foods that the intestines can’t handle on their own, bacteria produce energy for us, and the amount they produce is noteworthy. Germ-free mice weigh significantly less than conventionally raised mice, but once bacteria begin to colonize them they have a 60 percent weight gain, despite not eating more food than regular mice. One of the mechanisms by which they accomplish this is a process known as fermentation. Think of the intestine as a bioreactor where bacteria ferment fiber, carbohydrates, and proteins that were not digested and absorbed in the small intestine. The end-products of this process are called short-chain fatty acids (SCFA), and three of them are very important to different aspects of human energy metabolism: acetate, butyrate, and propionate. Intestinal cells rapidly absorb SCFA and use them as an energy source to stay fueled. SCFA are also transported very rapidly to the liver, where they are transformed into critical compounds involved in energy expenditure and energy storage. SCFA help determine how and when we use the energy obtained from food, and, importantly, when to store it as fat. Thus, it’s not surprising that alterations in the production of SCFA have been associated with obesity, both in