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

by Ed Yong

But without the immune system’s full selective powers, how can a mammalian baby ensure that it gets the right communities? Its mother helps. Mother’s milk is full of antibodies which control the microbial populations of adults – and babies take up these antibodies during breastfeeding.

Recall that every individual animal, whether human or coral, is an ecosystem in itself. It grew up under the influence of its microbes and continues to engage them in a lively negotiation.

Remember also that these partners often have competing interests and that hosts need to control their microbes, keeping them in line by offering the right food, confining them to specific tissues, or placing them under immune surveillance. Now imagine that something disrupts that control.

Sometimes it becomes, quite literally, inflammatory, as microbes over-stimulate the immune system or wheedle their way into tissues where they don’t belong. In other cases, microbes might start to opportunistically infect their hosts. That’s dysbiosis. It’s not about individuals failing to repel pathogens, but about breakdowns in communication between different species – host and symbiont – that live together.

Without fibre, the lean communities couldn’t establish themselves or stop the mice from putting on weight. They could only infiltrate the guts of mice that ate healthily. The old dietary advice still stands, overenthusiastic headlines be damned.

An important lesson emerged: microbes matter but so do we, their hosts. Our guts, like all ecosystems, aren’t defined just by the species within them but also by the nutrients that flow through them.

The immune system, for all its intricacy, is a lot like that dial. It works like an ‘immunostat’, which, rather than stabilising temperature, stabilises our relationships with our microbes.15 It manages the benign trillions that live with us, while thwarting invasions by an infectious minority. If it is set too low, it becomes relaxed, missing threats and leaving us open to infections. If it is set too high, it becomes jumpy, falsely attacking our own microbes and triggering chronic inflammation. It must tread a fine line between these extremes, balancing the cells and molecules that induce inflammation with those that repress it. It must react without overreacting. But over the last half-century, we have gradually pushed our immunostats to higher settings through a combination of sanitation, antibiotics, and modern diets. We’ve ended up with immune systems that go berserk at harmless things like dust, molecules in our food, our resident microbes, and even our own cells.

was the combination of genetic susceptibility, viral infection, immune problems, environmental toxin, and their microbiome that gave them IBD.

All of these changes have been consistently linked to a higher risk of allergic and inflammatory diseases, and all of them reduce the range of microbes that we are exposed to. A single dog can have a huge effect. When Susan Lynch hoovered up the dust of 16 homes, she found that those without furry pets were ‘microbial deserts’. Those with cats were far richer in microbes, and those with dogs were richer still.23 It turned out that man’s best friend is a chauffeur for man’s old friends.

This is the essence of the hygiene hypothesis and its various spin-offs: exposure to a broader range of microbes can change the microbiome and suppress allergic inflammation – at least in mice.

This might explain why C-section babies are more likely to develop allergies, asthma, coeliac disease, and obesity later in life.

Saturated fats can nourish inflammatory microbes. So can two common food additives, CMC and P80, used to lengthen the shelf life of ice cream, frozen desserts, and other processed foods; they also suppress anti-inflammatory bugs.25 Dietary fibre has the opposite effects. This is a catch-all term for various complex plant carbohydrates that our microbes can digest. Fibre has been a mainstay of health advice ever since Denis Burkitt, an Irish missionary surgeon, noticed that rural villagers in Uganda eat up to seven times more fibre than Westerners. Their stools are five times heavier, but pass through the intestine twice as quickly.

We now know that when bacteria break down fibre, they produce chemicals called short chain fatty acids (SCFAs); these trigger an influx of anti-inflammatory cells that bring a boiling immune system back down to a calm simmer. Without fibre, we dial our immunostats to higher settings, predisposing us to inflammatory disease. To make matters worse, when fibre is absent, our starving bacteria react by devouring whatever else they can find – including the mucus layer that covers the gut. As the layer disappears, bacteria get closer to the gut lining itself, where they can trigger responses from the immune cells underneath. And without the restraining influence of the SCFAs, those responses can easily build to extreme proportions.27

Meanwhile, other studies have shown that even short courses of antibiotics can change the human microbiome.

Some species temporarily disappear. The overall diversity plummets. Once we stop taking the drugs, our communities bounce back to something that’s largely, but not entirely, like their original state. As in Sonnenburg’s fibre experiment, each knock leaves the ecosystem slightly dented. As more knocks land, the dents deepen.

Ironically, this collateral damage can pave the way for more disease. Remember that a rich, thriving microbiome acts as a barrier to invasive pathogens. When our old friends vanish, that barrier disappears. In their absence, more dangerous species can e...

This is why C. difficile mostly affects people who have been taking antibiotics, and why most infections happen in hospitals, nursing homes, or other healthcare settings. Some call it a man-made disease, associated with the very institutions that are meant to keep us healthy. It is the unintended consequence of an indiscriminate approach to killing microbes, akin to blitzing a weed-infested garden with pesticides and hoping that flowers will grow in their stead; often, you just get more weeds.33

We have taken cleanliness to mean a world without microbes, without realising the consequences of such a world. We have been tilting at microbes for too long, and created a world that’s hostile to the ones we need.

H. pylori, being easy to detect, is the canary in a coal mine. It warns us that other microbes might be going missing right under our noses.

These lessons in humility are worth remembering when we think about the medical implications of the microbiome, or the absurdly long list of conditions that have been linked to it.

The microbiome is not a constant entity. It is a teeming collection of thousands of species, all constantly competing with one another, negotiating with their host, evolving, changing. It wavers and pulses over a 24-hour cycle, so that some species are more common in the day while others rise at night. Your genome is almost certainly the same as it was last year, but your microbiome has shifted since your last meal or sunrise.

The average human swallows around a million microbes in every gram of food they eat. Since microbes are everywhere, virtually every source of food, whether a patch of water, the stem of a plant, or the flesh of another animal, is a potential source of new symbionts.4

Many familiar animals, including cows, elephants, pandas, gorillas, rats, rabbits, dogs, iguanas, burying beetles, cockroaches, and flies, regularly eat each other’s faeces – a practice known as coprophagy. For skin microbes, simple contact can suffice.

The seemingly infinite range of transmission routes through which animals pick up microbes from one another all serve the same imperative: the need to move microbes from one generation of hosts to the next.

squirrel might eat nuts aplenty one season and nothing at all the next. I might wolf down a croissant today, and prod at a salad tomorrow. And with each new meal or mouthful, we select for microbes that are best at digesting whatever we’ve just eaten. They react with incredible speed.

They must cope with seasonal menus. They encounter feasts and famine. They’ll be forced to try unfamiliar foods. A rapidly adapting microbiome helps cope with all of these challenges. It provides flexibility and stability in a changing and uncertain world.

When you were born, you inherited half your genes from your mother and half from your father. That’s your lot. Those inherited bits of DNA will remain with you for all of your life, with no further additions or omissions.

Bacteria have been carrying out these horizontal gene transfers, or HGT for short, for billions of years, but it wasn’t until the 1920s that scientists first realised what was happening.

It is said that cities are hubs of innovation because they concentrate people in the same place, allowing ideas and information to flow more freely. In the same way, animal bodies are hubs of genetic innovation, because they allow DNA to flow more freely between huddled masses of microbes.

That is the power of symbiosis: it allows gradual mutations in microbes to produce instant mutations in hosts.

prebiotics like inulin are in plentiful supply in onions, garlic, artichokes, chicory, bananas and other foods.

No bacterium exists in a vacuum. Different species often form complex networks that feed and support each other in co-dependent ways.

So, perhaps a smarter approach to making probiotics is to create a community of microbes that work well together.

Indeed, we humans are unusual in our aversion to faeces. Many other animals practise coprophagy, and will gamely swallow each other’s dung and droppings to acquire microbes.

This makes the microbiome the only organ that can be replaced without surgery.

There’s a popular saying among doctors: there’s no such thing as alternative medicine; if it works, it’s just called medicine.

The growing acceptance of FMT among mainstream medics epitomises this idea. Khoruts

C-diff is the exception that proves the rule.36 People get it after taking antibiotics, and they typically control it by taking even more antibiotics. This pharmacological carpet-bombing clears many of the native bacteria from their guts.

When a donor’s microbes arrive in this wasteland, they find few competitors, and certainly few that are as well adapted to the gut as they are. They can easily colonise.

Ideally, there would eventually be a series of RePOOPulates, perhaps tailored to different diseases.

These are not one-size-fits-all solutions. They will need to be personalised.

The entire ecosystem – host, microbes, nutrients, everything – must be manipulated through a multi-pronged approach.

Here is what that might look like. If people have high cholesterol levels, doctors might prescribe drugs called statins, which block a human enzyme that’s involved in creating cholesterol. But Stanley Hazen has shown that gut bacteria make good targets, too. Some of them can transform nutrients like choline and carnitine into a chemical called TMAO, which slows the breakdown of cholesterol.50 As TMAO levels build, so do fatty deposits in our arteries, leading to atherosclerosis – a hardening of arterial walls – and other heart problems. Hazen’s team have now found a chemical that can stop this process by preventing the bacteria from making TMAO – all without harming them. Perhaps this chemical, or something like it, will sit alongside statins in tomorrow’s medicine cabinet: two complementary drugs, one that targets the human half of the symbiosis, and another that nudges the microbial half.

And that’s just a sliver of the full potential of microbiome medicine. Imagine we’re ten, twenty, maybe thirty years into the future. You see a doctor. You’ve been feeling anxious, so she prescribes a bacterium that’s been shown to affect the nervous system and repress anxiety. Your cholesterol is a little high, so she adds another microbe that makes and secretes a cholesterol-lowering chemical. The levels of secondary bile acids in your gut are unusually low, leaving you vulnerable to a C-diff infection – best to include a strain that produces these acids. Your urine contains molecules that are signs of inflammation, and since you also have a genetic predisposition to IBD, she adds a bug that releases anti-inflammatory molecules. She chooses these species not just for what they can do, but because she predicts that they will interact well with your immune system and your existing microbiome. She also adds a supporting cast of other bacteria chosen to prop up the therapeutic core, and she suggests some diet...

Could either have known that Wolbachia would turn out to be one of the planet’s most successful bacteria?

So, here’s the irony: toilets that are cleaned too often are more likely to be covered in faecal bacteria.