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

by Giulia Enders

  Science has the same problem when investigating the microbiome that the Google generation regularly faces. We ask a question and six million sources send us simultaneous answers. We don’t respond by telling them to form an orderly line. We have to sort them shrewdly into categories, weed out the irrelevant ones, and recognize important patterns. One important step in this direction was the discovery of the three human enterotypes in 2011.

  Researchers in Heidelberg, Germany, were using cutting-edge technology to investigate the human gut biome. They expected to see the usual picture: a chaotic mixture of many different bacteria, including a host of unknown species. What they actually discovered came as a surprise. Despite the great diversity, there was order. One of three families was always dominant in the realm of bacteria. Suddenly, the whole mess of more than a thousand families looked much more organized.

  The Three Gut Types

  A PERSON’S ENTEROTYPE depends on the family of bacteria that dominates the microbe population of their gut. The choice is between families that bask in the glory of the names Bacteroides, Prevotella, and Ruminococcus. Researchers identified these enterotypes distributed among Asians, Americans, and Europeans, irrespective of age or gender. In the future, enterotyping may help doctors predict a whole range of characteristics, such as the body’s response to soy, nerve resilience, or susceptibility to certain diseases.

  Practitioners of traditional Chinese medicine who were visiting the institute in Heidelberg at the time of this discovery recognized an opportunity to combine their ancient knowledge with modern medicine. Classical Chinese medical theory has always divided people into three groups according to how they react to certain medicinal plants, such as ginger. The families of bacteria in our bodies also have different characteristics. They break down food in different ways, produce different substances, and detoxify certain toxins but not others. Furthermore, they may also influence the gut flora by either encouraging or attacking bacteria from the other two groups.

  Bacteroides

  Bacteroides ARE THE best-known family of gut bacteria and often form the dominant population. They are experts in breaking down carbohydrates, and they possess a huge collection of genetic blueprints, which allows them to manufacture any enzyme they need to accomplish that task. Whether we eat a steak, munch a large salad, or chew on a raffia doormat in a drunken stupor, Bacteroides know straight away which enzymes they need. They are equipped to extract energy from whatever we ingest.

  Their ability to extract the maximum energy from everything and pass it on to us has led to the suspicion that they may be responsible for an increased tendency to gain weight. Indeed, Bacteroides do seem to like meat and saturated fatty acids. They are more common in the guts of people who eat plenty of sausages and the like. But, does having them in our gut make us fat, or does being fat lead to having them in our gut? This question remains to be answered. Bacteroides carriers are also likely to have a weakness for their colleagues, Parabacteroides. These bacteria are also particularly deft at passing on as many calories to us as possible.

  This enterotype is also notable, among other things, for its ability to produce particularly large amounts of biotin. Other terms for biotin include vitamin B7 and vitamin H. It was given the name vitamin H in the 1930s because of its ability to heal a certain skin condition caused by consuming too much raw egg white. “H is for healing” might not be the most creative mnemonic, but it is a useful one nonetheless.

  Vitamin H neutralizes avidin, a toxin found in raw eggs. It causes the skin disease in question by binding strongly with vitamin H, leaving the body deficient in that substance. So, eating raw eggs causes vitamin H deficiency, which in turn can lead to skin disease.

  I do not know who was eating enough raw eggs in the 1930s to lead to the discovery of this connection. I do, however, know who might possibly end up eating so much avidin in the future that they could have problems with vitamin H—pigs who accidently roam into a field of genetically modified corn. Genetic engineers have created transgenic corn with a gene that produces avidin to make it less susceptible to insect damage during storage. When pests—or stray pigs—consume the corn, they are poisoned. When the corn is cooked, it is no longer toxic, just like a good hard-boiled egg.

  Another indication that our gut microbes produce vitamin H is the fact that some people excrete more of it than they take in. Since no human cell is capable of producing this substance, the only possible explanation for this is that our bacteria are functioning as hidden vitamin H factories. Vitamin H is not only necessary for “healthy-looking skin, shiny hair, and strong nails,” as you might read on the packages of supplements you can buy in your local pharmacy. Biotin is also involved in some of the body’s vital metabolic processes. We need it to synthesize carbohydrates and fats for our body, and to break down proteins.

  Skin, hair, and nail problems are not the only effects of biotin deficiency. It can also cause depression, lethargy, susceptibility to infections, neurological disorders, and increased cholesterol levels in the blood. However, let me issue a serious WARNING here: the list of symptoms caused by any vitamin deficiency is formidable. Most people reading them feel the symptoms apply to them in some way. But it is important to remember that you can catch a cold or feel a bit lethargic without jumping to the conclusion that you have a biotin deficiency. And cholesterol levels are more likely to be raised by eating a big plate of bacon for breakfast than by eating the avidin in an undercooked egg.

  However, some people in higher-risk groups may well consider the possibility of a biotin deficiency. That includes anyone who takes antibiotics for an extended period, heavy drinkers, anyone who has had part of their small intestine removed, anyone reliant on dialysis, and people on certain kinds of medication. These people require more biotin than they can get from a normal diet. One healthy higher-risk group is pregnant women: developing babies use up biotin like aging refrigerators gobble up electricity.

  So far, no scientific studies have been carried out to investigate how much biotin our gut bacteria provide us with. We know that they produce some, and that antibacterial medications such as antibiotics can cause biotin deficiency. Investigating whether members of the Prevotella enterotype are more likely to suffer from a biotin deficiency than someone of the Bacteroides enterotype would be a pretty exciting research project. But, since the existence of the three different enterotypes was only discovered in 2011, there are many more pressing questions we need to answer.

  It is not only their good output that makes Bacteroides so successful; they also work hand in hand with others. Some species in the gut make a living by clearing away the waste left by Bacteroides. This is a win-win situation: Bacteroides work better in tidy surroundings, and the waste-disposal organisms have a secure source of income. On a different level, we find the composters. These organisms not only utilize waste products for their own ends, they also use them to make products that Bacteroides can use in turn. For some metabolic pathways, Bacteroides themselves take on the role of composter. For example, if they need a carbon atom to modify a molecule, they simply reach up and grab it out of the atmosphere in the gut. They always find what they are looking for, since carbon is a waste product of our metabolism.

  Prevotella

  IN MANY WAYS, the Prevotella family is the opposite of Bacteroides. Studies have shown that they are more common in the guts of vegetarians, but they also appear in moderate meat eaters and in convinced carnivores. Our diet is not the only factor that influences the colonization of our gut. But more about that presently.

  Prevotella also have a group of bacterial colleagues they prefer working with—Desulfovibrionales. Desulfovibrionales often have a long flagellum—a whiplike tail used to propel them along—and so, like Prevotella, they are adept at trawling through our mucus membranes looking for useful proteins. They then either eat those proteins or use them to build who-knows-what. Prevotella produce sulfur compounds when they work. The smell of these compounds is familiar, as we know
it from boiled eggs. If it weren’t for Desulfovibrionales whipping around with their propeller-tails, snapping up the sulfur, Prevotella would soon find themselves drowning in a sulfur swamp of their own making. Incidentally, this gas is not dangerous to human health. Our nose wrinkles at it as a precautionary measure as it can slowly become toxic as concentrations increase a thousandfold.

  Another substance that contains sulfur and has an interesting smell is the vitamin associated with this enterotype: thiamine. Also known as vitamin B1, this is one of the most widely recognized and important vitamins. Our brains require it not only to keep the nerves well nourished, but also to coat them in an electrically insulating layer of fat. This explains why a thiamine deficiency may be the cause of muscle tremors and forgetfulness.

  A very serious lack of vitamin B1 causes a disease called beriberi. It was described in Asia as early as AD 500. Beriberi means “I cannot, I cannot” in the Sinhalese language of Sri Lanka and refers to the fact that sufferers have difficulty walking due to nerve damage and muscle atrophy. It is now known that polishing rice removes the vitamin B1 it contains, and a diet made up predominantly of this kind of rice leads to an onset of symptoms within a few weeks.

  While not resulting in serious neurological or memory disorders, a less severe vitamin B1 deficiency can cause irritability, frequent headaches, and lack of concentration. More advanced cases can cause a susceptibility to edema and heart problems. But once again, beware: these symptoms can have many causes. They are only a reason for concern when they are unusually frequent or severe. They are rarely caused exclusively by a vitamin deficiency.

  Studying the symptoms of vitamin deficiencies provides a useful insight into the part played by vitamins in certain processes. Anyone whose diet does not consist exclusively of polished white rice or alcohol is usually well supplied. The fact that our gut bacteria help supply us with essential vitamins means they are far more than just a load of flagellating sulfur-poopers—and that is what makes them so fascinating.

  Ruminococcus

  OPINIONS ARE DIVIDED on this family—scientific opinions, at any rate. Some scientists who decided to investigate the existence of enterotypes for themselves found Prevotella and Bacteroides, but no Ruminococcus group. Others swear this third group exists, and yet others insist there is even a fourth or fifth group, or more. Such a state of affairs can really ruin the coffee break at a medical congress.

  Let’s agree for the sake of argument that there is at least a possibility that this group exists. Its proposed favorite food is the cell walls of plants. Possible colleagues include Akkermansia bacteria, which break down the mucins in mucus and absorb sugar pretty quickly. Ruminococcus produces a substance called haem, which the body needs for many things, including producing blood.

  One character who probably had problems producing haem was Count Dracula. A genetic defect has been identified in his home country, Romania, that results in symptoms that include a lack of tolerance to garlic, sensitivity to sunlight, and the production of red urine. This urine discoloration is caused by a defect in blood production that means sufferers excrete the unfinished precursors of blood production. Nowadays, those affected by the condition—called porphyria—are given medical treatment rather than the starring role in a horror story.

  Even if the Ruminococcus enterotype does not exist, there is no doubt that these bacteria are present in our gut. So, it is useful that we now know more about them—and about Dracula and red pee. Our bacteria-free laboratory mice have trouble forming haem, and so it stands to reason that bacteria are somehow important in this process.

  Now we are more familiar with the tiny world of the microbes in our gut. Their genes represent a huge pool of borrowed abilities. They help us digest our food, and they produce vitamins and other useful substances. We are just beginning to recognize enterotype commonalities and search for patterns. And we do this for one reason: 100 trillion tiny creatures reside in our gut and that cannot but have an effect on us. So, let’s now go one step further and explore the palpable effects they have on us. Let’s take a closer look at how these gut bacteria affect our metabolism, and examine which ones do us good and which ones do us harm.

  The Role of the Gut Flora

  SOMETIMES WE TELL fibs to our children. We do it because these little untruths are so nice. There’s the one about the man with the big white beard who arrives once a year on his tuned-up reindeer sleigh piled high with children’s presents, or the one about the Easter bunny hiding chocolate eggs in the garden. Sometimes, we don’t even realize when we are not telling the truth—like when we encourage a toddler to eat up: “One spoon for Daddy, one spoon for Mummy, one for Granny, and one for Granddad . . .” If we wanted to encourage Junior in a scientifically correct way, we would have to say, “One spoon for you, baby. A small part of the next spoon for your Bacteroides bacteria. An equally small part for your Prevotella. And a teeny-weeny bit for a few other microorganisms waiting in your tummy to be fed.” We might well send a friendly vote of thanks down to the micro-colleagues enjoying the meal in baby’s belly. After all, Bacteroides and company work hard to help keep baby well fed. And not only in infancy. Adults, too, receive nutrition back from their bacterial gut-dwellers, morsel by morsel. Gut bacteria process food that we cannot break down unaided and share the results with us.

  The idea that the bacteria in our gut might influence our overall metabolism, and therefore our weight, is only a couple of years old. The basic concept is that bacteria do not steal anything from us when they share our food in this way. Very few gut bacteria reside in the small intestine, where we break down our food for ourselves and absorb the nutrients from it. The highest concentration of bacteria is found where the digestive process is almost finished and all that remains is for the undigested remnants to be transported away. The farther you travel from the small intestine toward the final exit from the gut, the more bacteria you will find per square inch of gut membrane. It is our gut that makes sure this remains so. If the equilibrium is disturbed and large numbers of overconfident bacteria migrate to the small intestine, we have a case of what doctors call bacterial overgrowth. This relatively unexplored condition causes symptoms that can include severe bloating, abdominal pain, joint pain, and gastrointestinal infections, as well as nutrient deficiencies and anemia.

  In ruminants such as cows, this construction design is reversed. These large animals pride themselves on their ability to survive by eating only grass and a few other plants. No other animal on the farm would make fun of them for being puny vegans, so what is their secret? Cows keep their bacteria right at the top of their digestive tract. They don’t even bother trying to digest their food themselves first, but pass the complex plant carbohydrates straight on to Bacteroides and company. Their microbes turn these carbohydrates into an easily digested feast for the cow.

  It can be practical to keep your bacteria so close to the beginning of your digestive tract. Bacteria are rich in protein—so, from a food point of view, they are tiny little steaks. When they have finished their life’s work in the cow’s stomach, they slip farther down the system, where they are digested. They are a large source of protein for the cow—tiny microbial tenderloins, bred by themselves. Our bacteria are too far down the system to provide this practical steakhouse service so we pass them out of our gut undigested.

  Rodents keep their microbes as far down the system as we do, but are more loath to waste the bacterial protein they contain. Their simple solution is to eat their own feces. We don’t do that, preferring to buy meat or tofu at the supermarket to compensate for the fact that we are unable to process protein-rich bacteria in our large intestine. However, we still benefit from the work of our bacteria, even if we don’t digest them. Bacteria produce nutrients that are so tiny we can absorb them directly into the cells of our gut.

  Bacteria can also perform this service outside the gut. Yogurt is nothing other than milk that has been predigested by bacteria. Much of the sugar in the milk (lactose)
has already been broken down and transformed into lactic acid (lactate) and smaller sugar molecules. That is why yogurt is both sweeter and sourer than milk. The newly formed acid has another effect on the milk. It causes the milk protein to curdle, giving the yogurt its characteristic thick consistency. Predigested milk (yogurt) saves our body some work—we just have to finish off what the bacteria started.

  It is an especially good idea to employ those bacteria to predigest our food that manufacture healthy end products. Mindful yogurt manufacturers often use bacteria that produce more dextrorotatory (right-turning) than levorotatory (left-turning) lactic acids. Molecules of the two kinds of lactic acid are mirror images of each other. Feeding the human digestive system with levorotatory lactic acid molecules is like giving a left-handed pair of scissors to a right-handed person: they’re hard to handle. That is why it is a good idea to pick yogurt from the supermarket shelves that states on the container: “Contains mainly dextrorotatory [or right-turning] lactic acid.”

  Bacteria do more than just break down our food. They also produce completely new substances. Fresh cabbage, for example, is less rich in vitamins than the sauerkraut it can be turned into—those extra vitamins are made by bacteria. Bacteria and fungi are responsible for the taste, creamy consistency of, and holes in cheese. Bologna sausage and salami are often made with starter cultures—that’s butchers’ code for “We daren’t tell it you straight, but it is the bacteria (mainly Staphylococcus) that make it so tasty.” Lovers of wine or vodka appreciate the metabolic end product of yeasts—known as alcohol. The work of these microorganisms does not end in the wine barrel. Almost none of what a wine taster will tell you is actually to be found in the bottle. The wine’s bouquet, for example, develops so late because bacteria need time to do their work. They sit in waiting at the back of the tongue, where the process of transforming what we eat or drink begins. The substances they release during that process create the aftertaste so appreciated by the wine lover. And each connoisseur will experience a slightly different taste depending on the population of bacteria on their tongue. Still, it’s nice to get such an enthusiastic reaction to the presence of these much-maligned microbes.