Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (5 page)

It is not just in your mouth that microbes cause odor. It is everywhere there are microbes, which in fact is everywhere. In some places, armpits and groin, for instance, microbial concentrations are very high, and the populations are dominated by microbes that produce particularly smelly products. Although whole industries have arisen to control these odors, they are not accidental. From insects on up, our microbial odors identify who we are. They indicate who are our friends, our kin, our enemies, our lovers, or potential mates, and they tell us when might be a good time to mate. Mothers know the smell of their babies and vice versa. Smell is important, and it is mostly microbial in origin. It even determines who is attractive to mosquitoes. Once we fully understand how this works, we might harness that information to become more invisible or repulsive to those pests. But I have digressed.

After food leaves your mouth—where your teeth, saliva, enzymes, and friendly bacteria begin to break it up—it passes into your esophagus, a long tube that separates your mouth and pharynx from your stomach. No one thought bacteria resided in the esophagus until 2004, when we found a rich microbial community of dozens of species living there.

Food then passes into your stomach, where digestion begins with the help of acid and digestive enzymes. Despite strong acidity, bacteria also live there, including
H. pylori
(mentioned earlier), which when present usually dominates. Other species may be found in lower abundance. Your stomach makes hormones as if it were a gland like the thyroid. Its wall contains immune cells that help fight infection, just like your spleen or lymph nodes and colon.
H. pylori
plays a role in the production of acid and hormones and the state of immunity.

Next stop, your small intestine, a long tube that contains the major elements—detergents, enzymes, transporters—for breaking down and absorbing food into your body. This is where you digest most of your meals. Bacteria are present there, too, although in relatively small numbers, perhaps because high levels of microbial activity could interfere with the critical functions of nutrient digestion and absorption.

Eventually what remains of the food reaches your colon, where it finds wall-to-wall bacteria. Far and away, most of the microbes in your body live there. The numbers are astounding. One milliliter (about a thousandth of a quart) of colonic contents (and you have several thousand milliliters) contains many more bacteria than there are people on Earth. Your colon contains a universe of bacteria, densely packed, chemically active, accompanying you in your everyday journeys through life. You might think of this as part of the essential bargain of life: we provide them with room and board, and they help keep us alive. But that simplification is not entirely true. Many thousands of people have lost their colon and all of its bacteria because of illness or injury, yet they can live healthy lives for decades. So while this ocean of bacteria that you carry in your colon is very useful, it is not essential. (As mentioned, the same cannot be said for your complete microbiome; its total loss likely would be catastrophic.)

The microbes in your colon break down fibers and digest starch. In one sense, everything that has passed through to the end of your small intestine is on its way out, indigestible by you. But those hungry bacteria in your colon can metabolize quite a lot. They can digest the fibers in an apple that has passed through your small intestine and turn them into food—primarily to feed themselves—but some of their products, especially molecules called short-chain fatty acids, are released and actually feed you, starting with the cells in the wall of your colon. They nourish you, their innkeeper.

Up to 15 percent of the calories present in your food are extracted by the guest bacteria in your colon and used to feed you. Like all our resident microbes, they are more than casual or random guests; we coevolved to help each other. Among all mammals, even ones that separated from one another tens of millions of years ago, there are remarkable similarities in the types of colonic bacteria and in their functions.

The gut environment is warm, wet, and oozy, with numerous different neighborhoods occupied by specialized microbes. Some that make particular vitamins might live in particular niches, whereas ones that turn starches into simple sugars may live in much larger neighborhoods. There is competition. As in cities, prized parking spaces and spots in private schools are desirable. Many bacteria hungry for the same nutrients are equipped with identical enzymes and, like lions and cheetahs stalking the same prey, compete vigorously for similar foods. It seems to me that many want to lay their heads on the same soft layers of mucus and use the same limited number of hiding spaces protected from the harsh rain of stomach acid or bile. Meanwhile, many cells lining your gastrointestinal tract are sloughed off every day, so today’s hiding place may be tomorrow’s sinking ship. By the end, when the last products of digestion leave your body as feces, a mixture of bacterial cells is swept away along with the worn-out cells of your intestinal tract. Together, they and their fragments and water constitute the bulk of your stool.

To give you a sense of their importance in your metabolism, consider that nearly all of the chemicals present in your bloodstream are derived from the activities of your microbes. Bacteria also digest lactose, make amino acids, and break down the fibers in strawberries or, if you eat sushi, the fibers in seaweed.

Through their products, your microbes help you maintain stable blood pressure via specialized receptors located in your blood vessels (oddly, also found in your nose). These sensors detect small molecules created by the microbes that line your intestine. Responding to these molecules affects blood pressure. Thus, after eating, your blood pressure may go down. Could we one day have better treatments for high blood pressure by harnessing these bacteria? Very possibly.

Bacteria metabolize drugs. For example, millions of people around the world take digoxin, derived from the foxglove plant, to treat various heart conditions. How much of the drug reaches the bloodstream depends on the composition of each person’s microbiome; the gut is where digoxin undergoes its first chemical processing and then absorption. Variations in the chemistry have consequences. If levels are too low, the drug does not work. If levels are too high, a patient can experience additional heart problems, changes in color vision, and upset stomach. In the future, doctors may be able to gain control over how much digoxin reaches the blood by taming or augmenting gut microbes.

Some of your bacteria make vitamin K, which is necessary for your blood to clot but which is not made by your own cells. It may have been more efficient for the human body to rely on bacteria to produce vitamin K than to go through all of the metabolic costs in manufacturing it ourselves. So our ancestors who acquired vitamin K–producing bacteria were selected over cousins who had to invest in either making it or harvesting a substantial amount from plants. In a sense, our forebears outsourced a key metabolic function to our bacteria. We feed them and house them; they help clot our blood—a wonderful trade.

Some of your microbes even make an endogenous “Valium.” People dying of liver cancer often fall into a coma. But if they are given an agent that inhibits benzodiazapines (such as the drug Valium), they wake up. This is because a healthy liver breaks down a natural form of Valium made by microbes in the gut, but a sick liver does not, and the homegrown Valium goes straight to the brain and puts the person to sleep. Other microbes known to live in New Guinea highlanders allow their hosts to live on a diet that is 90 percent sweet potato, which is low in protein. Like bacteria that thrive on the roots of legumes, gut microbes in these New Guinea tribes are able to make proteins from sweet potatoes. They convert or “fix” atmospheric nitrogen found in the highlanders’ guts to make amino acids.

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In women, bacteria colonize and protect the vagina. Until recently medical scientists believed that only one group of bacteria, called lactobacilli, safeguarded the vagina in women of reproductive age from pathogens such as those that cause yeast infections. Indeed, lactobacilli shield the vagina by producing lactic acid, which lowers the pH of the vagina, making it slightly acidic and less hospitable to pathogens. It was assumed that those women whose vaginas are populated by different bacteria would be more prone to vaginal disorders. But now that DNA sequences of the vaginal bacteria from hundreds of healthy women are available, we know that there are five major types of vaginal microbiota, only four of which are dominated by a particular
Lactobacillus.
The fifth type essentially lacks
Lactobacillus
. A woman within this type has several other co-dominant bacterial species in her vagina, but contrary to long-held beliefs this does not make her more likely to develop vaginal disorders, and she is not part of a small minority. About a third of all women have this so-called abnormal mix of vaginal microbes.

Women without lactobacilli have a slightly higher vaginal pH, but their bacteria are just as good as lactobacilli at creating an environment unfriendly to intruders. This kind of functional substitution is probably occurring at sites all over the body, with different bacteria getting the same jobs done in different people.

In addition, we have learned that the bacterial populations in each woman’s vagina shift over time. For example, the bacterium
L. inners
may dominate during most of the month, but when a woman has her period, another bacterium,
L. gasseri,
will bloom, only to recede when her menses end. Seems straightforward enough, but this sort of pattern is an anomaly. The most common pattern is that there is no obvious pattern. Sometimes bacteria shift dominance in the middle of a woman’s cycle and the next month late in the cycle. Sometimes there are no changes. At other times
Lactobacillus
species take turns dominating the vagina in leapfrog fashion. And in some cases the “abnormal” bacteria dominate, only to disappear without apparent cause. We are still untangling the mystery of what drives these dramatic changes.

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Probably the most important service your microbes provide is immunity.

In fact, your microbes constitute an important third arm of the immune system. First, there is innate immunity, based on the fact that most of the microbes with which we are in contact have structural patterns that are “seen” by proteins and cells that guard our surfaces. Then adaptive immunity is based on the recognition of highly specific chemical structures. And microbial immunity is based on the microbes that are already in your body, your long-term residents, inhibiting outsiders through various mechanisms. We’ll explore each of these in more detail in coming chapters.

Interactions between the immune system and microbes begin at birth, shaping one another throughout your life. It makes sense. One essential property of your resident organisms is that they resist invaders. In essence, your friendly bugs are happy where they live and with the living they make. They do not want outsiders coming in. For example, when invaders try to gain a foothold in the intestines, they must first pass the gauntlet of your stomach acid, which is designed to kill most bacteria; the acid comes from the host, but its production is stimulated by resident bacteria, like
H. pylori.
If an outsider does reach your gut, it must find a source of food, a place to settle. But it’s crowded down there. Your resident bacteria don’t want to give up their hard-earned spots clinging to your intestinal walls. They certainly don’t want to share their meal. So they secrete substances, including their own antibiotics, which are poisonous to other bacteria.

Some invading microbes may gain a toehold for a few days and then be gone, a scenario that happens much more often than not. The fact is, your microbes keep things pretty stable. When you kiss someone, lots of organisms pass between you. But after a while—minutes, hours, days at most—you and your partner will look like you did, in terms of your microbes, before the kiss. There are exceptions (you can acquire harmful pathogens from your lover), and I will get to them. But your ability to resist invaders, even from someone attractive enough to kiss, normally is profound. The same goes for sexual intercourse. There is an exchange not just of fluids but of microbes, and there are changes in both hosts. But after a while, you and your lover are back to how you were before, like nothing (microbially speaking) ever happened. It is possible that some microbes may migrate between partners with regularity, but so far we don’t have any candidates, with the exception of pathogens, which often have evolved techniques for spreading among individual hosts.

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Even changes in diet may not change your microbes all that much. Over time, months and years, the composition of a person’s gut microbiome is relatively stable, but yours and mine are different. In one small study, people ate a Mediterranean diet for two weeks: high fiber, whole grains, dry beans/lentils, olive oil, and five servings of fruits and vegetables each day. This diet is strongly associated with a reduced risk of cardiovascular disease. The subjects gave blood samples for the analysis of lipids that have been correlated with heart disease and stool samples to determine which microbes were present before and after dieting. The researchers found a decrease in total cholesterol and a lowering of so-called bad cholesterol, or LDL—a good thing indeed. But the dieters’ microbes did not change. Instead each person appeared to have a unique microbial signature, like a fingerprint. The signature remained true, even after manipulation of his or her diet. Yet in other studies of diet, the changes in microbial populations were more significant. In a recent study, changing diet to exclusively plant origin or animal source led to extensive changes, but these lasted only as long as the person was consuming the special diet. We do not know if the diet were to be continued for a year whether the changes would become permanent. We will have to carry out many more studies to better understand the effects of diet on gut microbes. But for now it seems as if relative proportions of the various bacteria in your gut go up and down within discrete boundaries. Research is now aimed at understanding those borders and the extent to which yours and mine are the same and the degree to which they change over a lifetime.