Gut: The Inside Story of Our Body's Most Underrated Organ (Revised Edition)

by Giulia Enders

  There are many, many kinds of bacteria—some beneficial, others less so. Breast-feeding can help shift the balance toward the beneficial and reduce the risk of a later gluten intolerance, for example. A baby’s first population of gut bacteria prepares the way for the mature population by removing oxygen and electrons from the intestine. As soon as the environment is free of oxygen, the more typical bacteria of the gut can start to settle there.

  Breast milk is so beneficial that a more or less well-nourished mother need not do any more than suckle her baby to ensure it is receiving a healthy diet. When it comes to the nutrients it contains, breast milk provides everything that dietary scientists believe children need in order to thrive—it is the best dietary supplement ever. It contains everything, knows everything, and can do everything necessary for a child’s well-being. And, as if that weren’t enough, it has the added advantage of passing on a bit of Mom’s immune system to her offspring. Breast milk contains antibodies that can protect against any dangerous bacteria a child might make the acquaintance of (by licking the family pet, for example).

  Weaning is the first revolution experienced by a baby’s gut flora. Suddenly, the entire composition of Junior’s food supply is different. Clever old Mother Nature has equipped the typical bacteria that first colonize the infant gut with the genes needed to break down simple carbohydrates such as those in rice. Serve Junior complex, plant-based foods like garden peas, for example, and his baby flora will not be able to deal with them alone. He is now going to need new kinds of digestive bacteria. African children have bacteria that can manufacture all kinds of tools needed to break down even the most fibrous of plant-based foods. The microbes in the guts of children with a Western diet prefer to avoid such hard work—and they may do so with a clear conscience since their diet consists primarily of puréed baby food and small amounts of meat.

  Bacteria do not always manufacture the tools they need—sometimes they also borrow them. In Japan, the gut population has entered into a trade relationship with marine bacteria. They borrowed a gene from their sea-living colleagues that helps break down the kind of seaweed used in Japanese cuisine to make sushi, for example. This shows that the composition of our gut population can depend to a large extent on the tools we need to break down certain foodstuffs.

  Useful gut bacteria can be passed on through the generations. Anyone of European heritage who has experienced constipation after a blow-out session at the all-you-can-eat sushi bar will appreciate the advantage of inheriting Japanese seaweed-processing bacteria from someone in the family. However, it is not so easy to infuse yourself or your kids with a few sushi-digesting assistants. Bacteria have to like living in the place where they work.

  If we say a microorganism is particularly suited to our gut, we mean it appreciates the architecture of our gut cells, copes well with the climate, and likes the food on the menu. All three of these factors vary from person to person. Our genes help design our bodies, but they are not the chief architects of our microbial home. Identical twins share the same genes, but they do not have the same bacterial mix. They do not even have noticeably more similarities than other pairs of siblings. Our life-style, random acquaintances, illness, or hobbies all influence the shape of the populations inside our body.

  On the way to a relatively mature gut flora in our third year, we stick all sorts of stuff into our mouth—some of which will be useful and suited to us. We acquire more and more microorganisms, building up our population diversity from a couple of hundred species of bacteria to many hundreds of different gut-dwellers. That would be a pretty impressive inventory for any zoo, yet we acquire this variety without even thinking about it.

  It is now generally accepted that the first populations to colonize our gut lay the main foundations for the future of our entire body. Studies have shown the importance of those first few weeks of postnatal bacteria-collecting for the development of the immune system. Just three weeks after birth, the metabolic products of our gut flora can predict increased risks of allergies, asthma, or neurodermatitis in later life. How do we manage to pick up bacteria that are more harmful than beneficial to us so early in life?

  More than a third of all children in Western, industrialized countries are brought into the world by means of a convenient cesarean section. No squeezing through a narrow birth canal, no unpleasant side effects like perineal tearing, no delivering the afterbirth—it sounds like a fine thing. The initial contact experienced by children born by cesarean section is mainly with other people’s skin. They have to glean bacteria for their gut somehow, since their population will not develop from maternal microbes, like those of children born vaginally. They might end up with bacteria from Nurse Suzy’s right thumb, from the florist who sold Daddy that congratulatory bunch of flowers, or from Granddad’s dog. Suddenly, factors like the motivation of underpaid hospital cleaners become significant. Did they wipe down the telephones, tables, and bathroom faucets with loving care or a lack of conviction?

  Our skin flora is not as strictly controlled as that of the birth canal and is much more exposed to the outside world. Whatever gathers on the skin could soon end up in baby’s belly. These uninvited guests may include pathogens or weird types with strange ways of training the young immune system. Children born by cesarean section take months or even longer to develop a normal population of gut bacteria. Three-quarters of newborn babies who pick up typical hospital germs are those born by cesarean section. They also have an increased risk of developing allergies or asthma. One American study showed that administering Lactobacillus to those babies can reduce their risk of developing allergies. The same treatment has no effect at all on children born naturally—one could say they were dipped in the probiotic waters of the Styx while they were being born.

  By the age of seven, there is barely any discernible difference between the gut flora of children born naturally and those born by cesarean section—the early stages, when the immune and metabolic systems are still impressionable, are long gone. Indeed, cesarean births are not the exclusive cause of less-than-ideal starting populations in the gut. Poor nutrition, unnecessary use of antibiotics, excessive cleanliness, or too much exposure to bad bacteria can also feature among the causes. In spite of all this, there is no reason for anyone to feel inadequate. We humans are large creatures, and there is no way we can exercise control over every aspect of our microscopic world.

  The Adult Gut Population

  IN TERMS OF our microbiota, we reach adulthood around the age of three. For a gut, being an adult means knowing how you work and what you like. When that stage has been reached, some gut microbes find themselves on a great expedition with us through our entire lives. We dictate the itinerary—by eating what we eat, reacting to stress, going through puberty, getting ill, and growing old.

  Those people who post pictures of their dinner on Facebook, only to be disappointed by the lack of “likes” from friends, are simply trying to appeal to the wrong audience. If there were such a thing as Facebug (Facebook for microbes!), a picture of your dinner would provoke an excited response from millions of users—and shudders of disgust from millions more. The menu changes daily: useful milk digesters contained in a cheese sandwich, armies of Salmonella bacteria hiding in a delicious dish of tiramisu. Sometimes we alter our gut flora, and sometimes it alters us. We are our flora’s weather and its seasons. Our flora can take care of us, or it can poison us.

  We are only now beginning to learn the impact the gut-based bacterial community can have on an adult human. In this respect, scientists know more about bees than about human beings. For bees, having more diverse gut bacteria has been a more successful evolutionary strategy. They were only able to evolve from their carnivorous wasp ancestors because they picked up new kinds of gut microbes that were able to extract energy from plant pollen. That allowed bees to become vegetarians. Beneficial bacteria provide bees with an insurance policy in times of food scarcity: they have no trouble digesting unfamiliar nectar from far-flung fie
lds. More specialized digesters are not so well equipped. Times of crisis highlight the advantage of hosting a good microbial army. Bees with well-equipped gut flora can deal with parasite attacks better than those without. Gut bacteria are an incredibly important factor in this evolutionary survival strategy.

  Unfortunately, we cannot simply transfer these results to humans. Humans are not bees; they are vertebrates and they use Facebook. So researchers have to go back to square one. Scientists investigating our gut bacteria have to learn to understand an almost completely unknown world and its interaction with the world outside. First, they need to know who is living inside our gut.

  So let’s take a closer look. Who exactly are these characters?

  Biologists love to put things in order—from the contents of their own desks to the entire contents of the world. They begin by sorting everything into two large drawers: one for living things and the other for non-living things. They then go on to divide everything in the first drawer into three categories: eukaryotes, Archaea, and bacteria. Representatives of all three groups can be found in the gut. I am not promising too much when I say each of the three groups has its own kind of charm.

  Eukaryotes are made up of the largest and most complex cells. They can be multicellular and grow to a pretty impressive size. A whale is a eukaryote. Humans are eukaryotes. Ants are too, incidentally, although they are much smaller than we are. Modern biologists divide eukaryotes into six subgroups: crawly amoeboid microbes, microbes with pseudopodia (foot-like protrusions that aren’t real feet), plant-like organisms, single-celled organisms with little mouth-like feeding grooves, algae, and opisthokonts.

  For those unfamiliar with the term opisthokont (it comes from the Greek words for “rear” and “pole”), it describes the group that includes all animals—humans as well—and also fungi. So, the next time you meet an ant in the street you can give it a friendly wave as a fellow opisthokont. The most common eukaryotes found in the gut are yeasts, which are also opisthokonts. We are familiar with yeast as a rising agent for bread, but there are many other kinds.

  Archaea are kind of in-betweeners. Not really eukaryotes, but not really bacteria, either. Their cells are small and complex. If this description seems a little vague, it may help if I say that the Archaea are pretty rad characters. They love the extreme things in life. Some are hyperthermophiles, which feel right at home in temperatures of more than 212 degrees Fahrenheit (100 degrees Celsius) and are often to be found hanging out near volcanoes. The acidophiles among the Archaea like to paddle around in highly concentrated acid. Barophiles (also called piezophiles) thrive under pressure and have specially adapted cell walls to allow them to live on the deep sea floor. Halophiles are at home in extremely salty water (they love the Dead Sea). The rare characters among the Archaea that can be cultured in the lab are the cryophiles, which love the cold. They like laboratory freezers that keep them at a cozy minus 112 degrees Fahrenheit (minus 80 degrees Celsius). There is one species of Archaea often found in our gut that thrives on the waste products of other gut bacteria and can glow.

  Returning to the main topic: bacteria make up more than 90 percent of the population of our gut. Biologists divide bacteria into more than twenty phyla or lineages. Members of different phyla are sometimes about as similar as human beings are to excavates (single-cell microbes with feeding grooves)—that is to say, not very. Most of the inhabitants of our gut belong to one of five phyla: mainly Bacteroidetes and Firmicutes, with a smattering of Actinobacteria, Proteobacteria, and Verrucomicrobia. These phyla are further divided into increasingly specific categories, until we eventually reach the level of the bacteria family. Members of a given family are relatively similar to each other. They eat the same food, keep similar company, and have similar abilities. Individual family members have impressive names like Bacteroides uniformis, Lactobacillus acidophilus, or Helicobacter pylori. The bacteria kingdom is huge.

  Whenever scientists search humans for a particular bacterium, they constantly come across new, previously unknown species. Or they discover known species in unexpected places. In 2011, a group of researchers in the United States decided to examine the flora of volunteers’ belly buttons, just for fun. One subject’s navel was found to contain bacteria that were previously known to live only in the seas off the coast of Japan—despite the fact that the volunteer had never even been to Asia. Globalization is not just your local corner shop turning into a McDonald’s—it affects even the contents of our navels. Every day, billions and billions of foreign microorganisms fly round the world without paying a single cent for their tickets.

  Everyone has their own personal collection of bacteria. It could even be described as a unique bacterial fingerprint. If you were to take swabs from a dog and analyze the genes of its bacteria, the dog’s owner could be easily identified with reasonable certainty. The same is true of computer keyboards. Anything we come into regular contact with carries our microbial signature. Everyone has some outlandish items in their collection that almost no one else will share.

  Rough overview of the three most important phyla of bacteria and their subgroups. Lactobacilli are Firmicutes, for example.

  The microbial landscape in our gut is just as unique and individual. So, how are doctors supposed to know what is beneficial and what is harmful? Uniqueness like this presents researchers with a problem. If they are trying to ascertain what influence our gut bacteria have on our health, it is no use finding out that Mr. Smith is carrying a strange Asian species and several other weird microbes in his gut. Scientists need to identify patterns to deduce facts from them.

  So, since scientists are faced with more than a thousand different families of bacteria, they must decide whether they need to identify just rough lineages or whether they should look at every paid-up member of the Bacteroides bacteria family individually. E. coli and its evil twin EHEC are members of the same family, for example. The differences between them are infinitesimally small—but they are very tangible: E. coli is a harmless gut-dweller, while EHEC causes severe internal bleeding and diarrhea. It always makes sense to examine families or lineages when you want to know what damage individual bacteria can wreak.

  The Genes of Our Bacteria

  GENES ARE POSSIBILITIES. Genes are information. Genes can be dominant, forcing features on us, or they can just offer their abilities for us to use or not. But most of all, genes are plans. They are incapable of doing anything unless they are read and implemented. Implementation of some of these plans is obligatory—they decide whether we are a human being or a bacterium, for example. Others (say, liver spots) can be left on the back burner for years and yet others might be carried for a lifetime without ever being expressed—for example, genes for large breasts. Some people might consider that a pity, others a blessing.

  Taken together, our gut bacteria have 150 times more genes than a human being. This massive collection of genes is called a biome. If we could pick 150 different living things, parts of whose genetic blueprints we would like to possess, what would we choose? Some people might opt for the strength of a lion, the wings of a bird, the hearing of a bat, or the practical mobile home of a snail.

  There are many reasons why it would be more practical to opt for bacterial genes instead. They can be taken in easily via the mouth, unfurl their abilities in the gut, and even adapt to our lifestyle. Nobody needs a snail’s mobile home all the time, and no one needs breast-milk-digestion helpers forever. The latter disappear gradually after weaning. It is not yet possible to examine all the genes of our gut bacteria at once. However, it is possible to search specifically for individual genes, if you know what you are looking for. We know that babies contain more active genes for digesting breast milk than adults do. The guts of obese people are often found to contain more bacterial genes involved in breaking down carbohydrates. Older people have fewer bacterial genes for dealing with stress. In Tokyo, gut bacteria can help digest seaweed, and in Toronto, they probably can’t. Our gut bacteria paint a rough port
rait of who we are: young, chubby, or Asian, perhaps.

  The genes of our gut bacteria also inform us about our body’s abilities. The pain-relief drug acetaminophen can be more toxic for some people than others: some gut bacteria produce a substance that influences the liver’s ability to detoxify the drug. Whether you can pop a pill to cure your headache without a second thought is decided partially in your gut.

  Similar caution should be exercised with general dietary tips. Soy’s ability to protect against prostate cancer, cardiovascular disease, or bone disorders, for example, has now been proven. More than 50 percent of Asians benefit from this effect. Among people of European heritage, the beneficial effect is found among only 25 to 30 percent of the population. This cannot simply be explained by human genetic differences. The difference is due to certain bacteria. They are found more commonly in the guts of Asians, where they are able to coax the health-promoting essence out of tofu and other soy products.

  It is great for science when it identifies the individual bacterial genes that are responsible for this beneficial effect. In such cases, science can be said to have come up with an answer to the question of how gut bacteria influence our health. But we want more than that. We want to understand the big picture. If you look at all the bacterial genes so far discovered, the small individual groups of genes responsible for breaking down painkillers or soy products fade into the background. The common features they share dominate the picture. Every microbe contains many genes involved in breaking down carbohydrates or proteins and in producing vitamins.