I Contain Multitudes: The Microbes Within Us and a Grander View of Life

by Ed Yong

When we look at beetles and elephants, sea urchins and earthworms, parents and friends, we see individuals, working their way through life as a bunch of cells in a single body, driven by a single brain, and operating with a single genome. This is a pleasant fiction. In fact, we are legion, each and every one of us. Always a “we” and never a “me”. Forget Orson Welles, and heed Walt Whitman: “I am large, I contain multitudes.”5

Let me stress: all the visible organisms that we’re familiar with, everything that springs to mind when we think of “nature”, are latecomers to life’s story. They are part of the coda. For most of the tale, microbes were the only living things on Earth. From March to October in our imaginary calendar, they had the sole run of the planet.

They released oxygen as a waste product, pumping out so much of the gas that they permanently changed the atmosphere of our planet.

Even now, the photosynthetic bacteria in the oceans produce the oxygen in half the breaths you take, and they lock away an equal amount of carbon dioxide.

there are more bacteria in your gut than there are stars in our galaxy.3

All eukaryotes share these traits because we all evolved from a single ancestor, around two billion years ago.

Before that point, life on Earth could be divided into two camps or domains: the bacteria, which we already know about, and the archaea, which are less familiar and have a fondness for colonising inhospitable and extreme environments.

Then, on one fateful occasion, a bacterium somehow merged with an archaeon, losing its free-living existence and becoming entrapped forever within its new host. That is how many scientists believe eukaryotes came to be. It’s our creation story: two great domains of life merging to create a third, in the greatest symbiosis of all time. The archaeon provided the chassis of the eukaryotic cell while the bacterium eventually transformed into the mitochondria.

The latest estimates suggest that we have around 30 trillion human cells and 39 trillion microbial ones – a roughly even split.

Most microbes are not pathogens. They do not make us sick. There are fewer than 100 species of bacteria that cause infectious diseases in humans;8 by contrast, the thousands of species in our guts are mostly harmless.

Your cells carry between 20,000 and 25,000 genes, but it is estimated that the microbes inside you wield around 500 times more.9 This genetic wealth, combined with their rapid evolution, makes them virtuosos of biochemistry, able to adapt to any possible challenge.

microbes are lords of decay.

the animals of Asia suddenly gave way to the very different fauna of Australasia, as if these two islands were separated by an invisible barrier (which would later be called the Wallace Line).

Wallace’s observations and specimens led him towards the defining insight of biology: that species change. “Every species has come into existence coincident both in space and time with a pre-existing closely allied species,” he wrote, repeatedly and sometimes in italics.

Islands are where you go if you want to find life at its most outlandish, gaudy, and superlative. Their isolation, restricted boundaries, and constrained size allow evolution to go to town.

It’s now debatable if that core exists.18 Some species are common, but none is everywhere. If there is a core, it exists at the level of functions, not organisms.

Speaking of palms, your right hand shares just a sixth of its microbial species with your left hand.

Scent, health, digestion, development, and dozens of other traits that are supposedly the province of individuals are really the result of a complex negotiation between host and microbes.

In our imaginary calendar, which condenses Earth’s history into a year, bacteria first appeared in mid-March.

In the 1730s, when Carl Linnaeus began classifying all life, he lumped all microbes into the genus Chaos (meaning formless) and the phylum Vermes (meaning worms).

Most bacteria, it said, are decomposers that return nutrients from decaying organic matter back to the world.

If one partner benefited at the expense of the other, it was a parasite (or a pathogen if it caused disease). If it benefited without affecting its host, it was a commensal. If it benefited its host, it was a mutualist. All these styles of coexistence fell under the rubric of symbiosis.

Symbiosis, with its themes of cooperation and teamwork sat uneasily within this framework of conflict and competition. Nor did it fit with the idea of microbes as villains.

“The knowledge that micro-organisms can be helpful to man has never had much popular appeal, for men as a rule are more preoccupied with the danger that threatens their life than in the biological forces on which they depend,” he wrote. “The history of warfare always proves more glamorous than accounts of co-operation.

Jo Handelsman provided one in 1998 – metagenomics, the genomics of communities.

our microbes control the storage of fat and the creation of new blood vessels, and that obese individuals have different gut microbes to lean ones.

the microbe told the mice how to use their own genes to make a healthy gut.8 Scott Gilbert, a developmental biologist, calls this idea co-development.

choanoflagellates.

Choanos reproduce by dividing in two, but sometimes the two daughter cells fail to split completely and end up connected by a short bridge. This happens again and again, until there’s a sphere of linked cells, enveloped in a single sheath. That’s the rosette. It would be an obscure piece of biological trivia were it not for the fact that choanos are the closest living relatives of all animals.

So, she fed the choanos with a battery of antibiotics and, to her surprise, disrupted their ability to form colonies entirely. If they were reluctant to form colonies before, they were now utterly set against it. Something about the bacteria had been making them sociable.

Out of 64 species, just one bacterium restored the rosettes.

The team have since identified several other molecules from many other microbes that can shove the choanos towards colonial life.

The oceans are swarming with baby animals that only complete their life cycles upon contact with bacteria – and often P-luteo in particular.

It means that: (a) there’s a solid surface, (b) which has been around for a while, (c) isn’t too toxic, and (d) has enough nutrients to sustain microbes. Those reasons are as good as any to settle down. The better question would be: Why wouldn’t you rely on bacterial cues? Or better still: what choice do you have?

If you list all the species in a particular microbiome, you can tell who’s there. If you list all the genes in those microbes, you can tell what they are capable of.28 But if you list all the chemicals the microbes produce – their metabolites – you can tell what those species are actually doing.

Biologists speak of a “gut–brain axis” – a two-way line of communication between the gut and the brain.

psychobiotics

“it’s highly unlikely that we’ll come up with a cocktail of probiotics that will treat severe depression. But there’s potential at the milder end of the spectrum.

The rabies virus infects the nervous system and makes its carriers violent and aggressive; if they lash out at their peers, and inflict bites and scratches, they pass the virus on to new hosts.

The brain parasite Toxoplasma gondii is another puppetmaster. It can only sexually reproduce in a cat; if it gets into a rat, it suppresses the rodent’s natural fear of cat odours and replaces it with something more like sexual attraction. The rodent scurries towards nearby cats, with fatal results, and T. gondii gets to complete its life cycle.50

H. G. Wells wrote about this in 1930: “Every symbiosis is, in its degree, underlain with hostility, and only by proper regulation and often elaborate adjustment can the state of mutual benefit be maintained. Even in human affairs, the partnerships for mutual benefit are not so easily kept up, in spite of me being endowed with intelligence and so being able to grasp the meaning of such a relation. But in lower organisms, there is no such comprehension to help keep the relationship going. Mutual partnerships are adaptations as blindly entered into and as unconsciously brought about as any others.”

every body part on every species has its own zoological terroir – its unique combination of temperature, acidity, oxygen levels, and other factors that dictate what kinds of microbe can grow there.

And up to a fifth of insect species enclose their symbionts within special cells called bacteriocytes.

But most viruses infect and kill microbes instead.

Phages don’t infect animals, and they far outnumber the viruses that do. The trillions of microbes in your gut can support quadrillions of phages.

Rohwer suspects that animals, by changing the chemical composition of their mucus, could potentially recruit specific phages, which kill some bacteria while providing safe passage to others.

Phages are 15 times more likely to find a victim if they stick to mucus. And since mucus is universal in animals, and phages are universal in mucus, this partnership probably started at the dawn of the animal kingdom.

You could view this as the immune system calibrating the microbiome: the more microbes there are, the more strongly the immune system pushes back against them. Alternatively, you could say that the microbes are calibrating the immune system, triggering responses that create a suitable niche for themselves while pushing out their competitors.

The immune system’s main function is to manage our relationships with our resident microbes. It’s more about balance and good management than defence and destruction.

To allow our first microbes to colonise our newborn bodies, a special class of immune cells suppresses the rest of the body’s defensive ensemble, which is why babies are vulnerable to infections for their first six months of life.30 It’s not because their immune system is immature, as is commonly believed: it’s because it is deliberately stifled to give microbes a free-for-all window during which they can establish themselves.