Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (4 page)

Under other conditions, many different bacteria help each other. Perhaps in a fast-moving stream, bacterium A eats the waste products of bacterium B and also sticks to the edges of rocks. Meanwhile bacterium C, which cannot stick, can adhere to bacterium A to avoid being swept away and helps anchor A in place. And B produces a compound nutritious to C. Now we have a situation where bacteria A, B, and C tend to cluster together, to the mutual benefit of all three.

Over the more than 4 billion years of bacterial evolution, with bacteria dividing and new cells coming along as often as every twelve minutes, and astronomical numbers of individual bacteria, there has been nearly infinite variation. From this endless process, individual bacteria have arisen that have populated all available niches on Earth.

Sometimes bacteria can live stably together, forming a consortium. These cooperative groups abound in the environment—in soil, in streams, on decaying logs, in hot springs—nearly everywhere there is life. The earliest unequivocal proof of ancient life is the existence of 3.5-billion-year-old fossilized “microbial mats” found in Australia, consortia that arranged themselves into large, layered sheets forming whole miniature ecosystems. In all likelihood, some layers performed photosynthesis, some breathed oxygen, some performed fermentation, and some ate unusual inorganic compounds. One species’ meat is another species’ poison; by settling into layers and combining their abilities, their concerted efforts lead to the benefit of all.

There are microbes that can form gelatin-like layers surrounding themselves. These thick gels are called
biofilms
. Their composition varies, but biofilms can protect the bacteria from drying out, or from excessive heat, or from the onslaught of immunity. The presence of biofilms helps explain bacterial persistence in harsh circumstances.

Microbes also form consortia and vast webs of cooperative functions not only in soils, oceans, and rocky surfaces but in animals as well. Such organisms in the human body are the central characters in my tale of “missing microbes.” The great biologist Stephen Jay Gould provided a frame of reference for all of terrestrial biology when he wrote: “… we live in the Age of Bacteria (as it was in the beginning, is now, and ever shall be, until the world ends)…” This is the context for human life, background and foreground.

3.

THE HUMAN MICROBIOME

Think for a moment about your vital organs. Your heart, brain, lungs, kidneys, and liver are complex structures that carry out essential functions that keep you alive. Every moment of the day and night they pump fluids, ferry wastes, deliver air and nourishment, and carry the signals that allow each of us to sense and move about the world. When any one of those organs fails, from disease or trauma, we die. It’s that simple.

But what if I were to tell you that you have another vital “organ” that helps keep you alive but that you have never seen. This organ is invisible. It is all over you, especially inside you, yet only recently have we started to appreciate the critical role it plays in keeping you healthy.

Perhaps most remarkable about this part of your body is that it seems completely alien. It does not derive from your obviously human cell lines, according to the blueprint of your human genes. Rather it’s composed of trillions of tiny life-forms, the microbes and their relatives that you just read about. Although you might think it a stretch to call this assemblage of microbes a vital organ, functionally the microbiome is just that. Unlike your heart and brain, its development begins not in the embryo but immediately at the moment of birth. It continues to develop in the first few years of life by acquiring ever more microbes from the people around you. But don’t be fooled. Losing your entire microbiome outright would be nearly as bad as losing your liver or kidneys. Unless you lived in a bubble, you would not last long at all.

The microbes living in you are not a random mix of all the species present on Earth. Rather, every creature has coevolved with its own collection of microbes that carry out many metabolic and protective functions. In other words, they work for us. There is a starfish microbiome and a shark microbiome, even a sponge microbiome. Reptiles such as lizards, snakes, and Komodo dragons each have unique microbiomes. Every owl, pigeon, and bowerbird has its own set of “bugs” devoted to its species. When the species survive, they survive. Mammals, too, from tiny lemurs to dolphins, dogs, and humans, are full of microorganisms specialized for keeping each of them alive and well.

These microbes provide the animals they inhabit with essential services. They are symbionts that help their hosts in exchange for being housed and fed. Termites can only digest wood because of the bacteria living in their guts. Cows absorb nutrients from the grasses they eat thanks to the microbes living in their four stomachs. Aphids, small insects that live on plants, have resident microbes, including a group called
Buchnera
, that began to live inside them more than 150 million years ago. They possess the key metabolic genes that enable making proteins, a trait that allows the aphids to use the sugar-rich sap from plants as a source of food. In turn, aphids provide a good home for
Buchnera
. It’s a win-win. Scientists have constructed the evolutionary family trees of
Buchnera
as well as that of aphids. When we compare the structures of the two trees, they are nearly identical. The probability that this could have occurred by chance is infinitesimal. The only answer is that they coevolved: aphids and their resident bacteria have reciprocally affected one another’s evolution for more than one hundred million years.

A close inspection of the mammalian microbiome reveals that, just as your genes for making red blood cells and proteins can be compared to similar genes in other mammals, your microbes also are part of a larger family tree. In that sense, microbial composition can be considered a marker of ancestry and helps explain why you are more apelike than cowlike. This raises an interesting question. Are you and I more apelike because of our mammalian genes or because of our microbial genes? We always assumed it to be the former, but maybe it is the latter. More likely, it is the sum of the two.

As described, your body is an ecosystem much like a coral reef or a tropical jungle, a complex organization composed of interacting life-forms. As with all ecosystems, diversity is critical. In a jungle, diversity means all the different types of trees, vines, bushes, flowering plants, ferns, algae, birds, reptiles, amphibians, mammals, insects, fungi, and worms. High diversity affords protection to all species within the ecosystem because their interactions create robust webs for capturing and circulating resources. Loss of diversity leads to disease or to collapse of the system when keystone species—ones that exert a disproportionately large effect on the environment relative to their abundance—are lost.

For example, when wolves were removed from Yellowstone National Park seventy years ago, the elk population exploded. Suddenly it was safe for elk to browse on, and ultimately denude, the tasty willows that line most riverbanks. Songbirds and beavers that depended on willows to nest and build dams dwindled in number. As rivers eroded, waterfowl left the region. With no wolf-kill carcasses to scavenge, ravens, eagles, magpies, and bears declined. More elk led to fewer bison due to competition for food. Coyotes came back to the park and ate the mice that many birds and badgers relied on. And so on, down a dense web of interactions perturbed when a keystone species was removed. This concept holds in the natural world as well as your microbiome, where the story of the disappearance of the stomach bacterium
Helicobacter pylori
that has colonized humans since time immemorial provides a cautionary tale.

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Your body is composed of an estimated 30 trillion human cells, but it is host to more than 100 trillion bacterial and fungal cells, the friendly microbes that coevolved with our species. Think about that: right now in your body bacterial cells substantially outnumber your own human cells. Seventy to ninety percent of all cells in your body are nonhuman. They reside on every inch of your skin, in your mouth, nose, and ears, in your esophagus, stomach, and especially your gut. Women have a rich assortment of bacteria in the vagina.

Of fifty known phyla of bacteria in the world, eight to twelve have been found in humans. But six of them, including Bacteroidetes and Firmicutes, account for 99.9 percent of the bacterial cells in your body. The most successful microbes—the winners when it comes to living with us humans—which descend from only these few lineages, comprise the basis of a core human microbiome. Over time, they have evolved specialized properties that allow them to thrive in and on particular niches in the human body. Such traits include the ability to survive acidity, exploit certain foods, and to prefer dry over wet conditions, or vice versa.

Collectively these bacteria weigh about three pounds, or the same as your brain, and represent perhaps ten thousand distinct species. No zoo in the United States contains more than one thousand species. The invisible zoo living on and inside you is far more diverse and complex.

When you were in your mother’s womb, you had no bacteria. But during the birth process and its aftermath, you were colonized by trillions of microbes. Later, we will consider this amazing process. Microbes go from zero to trillions in a short time. There is a well-choreographed succession from the founders to the later inhabitants over the first three years of life.

Ultimately, a unique population of residential microbes develops at each location on the inner and outer surfaces of your body. The crook of your elbow and the spaces between your toes are home to different species. The bacteria, fungi, and viruses on your arms are different from those in your mouth and in your colon.

Your skin is a huge ecosystem a bit larger than a half sheet of plywood, encompassing about twenty square feet of planes, folds, channels, and crannies. Most of these spaces are tiny, even microscopic. Your smooth skin, when viewed up close, may more closely resemble the surface of the moon, pocked by craters with hills and valleys. Which microbes take up residence on what piece of real estate depends on whether the area is oily like the face, moist like the armpit, or dry like the forearm. Sweat glands and hair follicles have their own microbes. Some of your bacteria eat dead skin, some make moisturizers from the oils secreted by your skin, and others keep harmful bacteria and fungi from invading your body.

As for your nose, researchers recently found the signature of many pathogens (disease-causing microbes) living peacefully in the nasal passage of healthy people. One,
Staphylococcus aureus
, is notorious. It can cause boils, sinusitis, food poisoning, and bloodstream infections. But it can also have a completely benign presence in your nose, just minding its own business. At any one time, at least a third of us, and maybe more, are carrying it.

Your intestinal tract is where most microbes in your body make their living, beginning from the top, in your mouth. If you look in the mirror, you can immediately see that there are discrete areas in your mouth, for example, your teeth, your tongue, your cheeks, and your palate. And each site has multiple surfaces. There is the top of your tongue and its bottom. Each tooth has multiple surfaces, and there is a juncture where the tooth descends into the gums. It is fair to say that for every surface there is a different population of bacteria normally living in your mouth. We know a lot about this from the Human Microbiome Project (HMP), a five-year program launched by the National Institutes of Health in 2007. Among the HMP goals was a large project to sequence the genetic material of microbes taken from nearly 250 healthy young adults. One of the take-home messages is that although the overall census of the bacteria present showed a lot of similarities among group members, everyone was unique. Our microbial differences far surpass the differences in our human genes. Our microbes are very personal, a reality we will come back to again and again. Still, there are general principles of organization. We can consider them in the gastrointestinal tract.

In the HMP, the mouth was extensively sampled. Certain families of organisms were found to be common in many sites, such as the Veillonellas, Streptococci, and Porphyromonads, but their distribution varied widely. And other organisms were present only in a limited area.

The richest zone in the mouth is the
gingival crevice,
the interface between tooth and gum. It is teeming with bacteria, many of which are anaerobic (they don’t like oxygen). They may be killed by it. It seems counterintuitive that we harbor a big population of oxygen-sensitive bacteria in our mouths, where oxygen-containing air is constantly passing, but it is true. This immediately tells us that there are special niches, some very small, where anaerobic bacteria may flourish.

Ever wonder why your breath smells different in the morning when you wake up? It’s because most of time when you sleep, you breathe through your nose. The air exchange in your mouth goes down, and the populations of anaerobic bacteria go up. They produce the chemicals, often volatile, that cause “morning mouth.” When you brush your teeth, you are removing tiny debris and whole populations of bacteria. Total counts go down, and the census distributions change. This cycle continues throughout the course of the day.