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

by Ed Yong

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

There are fewer than 100 species of bacteria that cause infectious diseases in humans;

Your cells carry between 20,000 and 25,000 genes, but it is estimated that the microbes inside you wield around 500 times more.

Many conditions, including obesity, asthma, colon cancer, diabetes, and autism, are accompanied by changes in the microbiome, suggesting that these microbes are at the very least a sign of illness, and at most a cause of it. If

Paracatenula is a master of regeneration. Cut it in two, and both ends become fully functional animals. The back half will even re-grow a head and brain. “Chop them up and you can get ten,” says Gruber-Vodicka. “That’s probably what they do in nature. They get longer and longer, and then one end breaks off and there are two.” This skill depends entirely on the trophosome, the bacteria inside it, and the energy they lock away. As long as a fragment of flatworm contains enough symbionts, it can produce an entire animal. If the symbionts are too scarce, the fragment dies. Counter-intuitively, this means that the only bit of the flatworm that can’t regenerate is the bacteria-free head. The tail will re-grow a brain but the brain alone will not produce a tail.

They affect the storage of fat. They help to replenish the linings of the gut and skin, replacing damaged and dying cells with new ones. They ensure the sanctity of the blood–brain barrier – a web of tightly packed cells that lets nutrients and small molecules pass from blood to brain, but bars the way to larger substances and living cells. They even influence the relentless remodelling of skeletons, in which fresh bone is deposited and old stuff is reabsorbed.

Nowhere is this steady influence more clear than in the immune system: the cells and molecules that collectively protect our bodies from infection and other threats.

Bacteroides fragilis

polysaccharide A

Mazmanian’s team later showed that PSA can prevent and cure inflammatory diseases like colitis (which affects the gut) and multiple sclerosis (which affects nerve cells), at least in mice.

Among Beaumont’s many observations, he noticed that St Martin’s mood affected his stomach. When the man became angry or irritable – and it’s hard to imagine not getting irascible when a surgeon is dangling food through the hole in your side – his rate of digestion changed. That was the first clear sign that the brain affects the gut. Almost two centuries later, this maxim seems all too familiar. We lose our appetite when our mood changes, and our mood changes when we feel hungry. Psychiatric problems and digestive problems often go hand in hand. Biologists speak of a “gut–brain axis” – a two-way line of communication between the gut and the brain.

Lactobacillus rhamnosus

Bifidobacterium

Drinking lots of alcohol makes the gut leakier, allowing microbes to more readily influence the brain – could that help to explain why alcoholics often experience depression or anxiety?

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

There’s a reason why all of these strategies are bad news for males. Wolbachia can only pass to the next generation of hosts in eggs; sperm are too small to contain it. Females are its ticket to the future; males are an evolutionary dead end. So it has evolved many ways of screwing over male hosts to expand its pool of female ones. It kills them, as in Hurst’s butterflies. It feminises them, as in Rigaud’s woodlice. It eliminates the need for them entirely by allowing females to reproduce asexually, as in Stouthamer’s wasps. None of these manipulations is unique to Wolbachia, but it is the only bacterium to use them all. Where Wolbachia does allow males to

Helicobacter pylori

They are harmless if they stay in the gut, but they can pass through the holes created by Bt toxins and invade the bloodstream. When the caterpillar’s immune system senses them, it goes berserk. A wave of inflammation spreads through the caterpillar’s body, damaging its organs and interfering with its blood flow. This is sepsis. It’s what kills the insect so quickly.

Just think about your gut. It’s a long and heavily folded tube that, if spread out fully, would cover the surface of a football field.

These measures – the mucus, the AMPs, and the antibodies – also determine the species that get to stay in the gut.27

To many scientists, however, warding off pathogens is just a bonus trick. 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

Mother’s milk is full of antibodies which control the microbial populations of adults – and babies take up these antibodies during breastfeeding.

Milk is one of the most astounding ways in which mammals control their microbes.

Milk is a mammalian innovation. Every mammal mother, whether platypus or pangolin, human or hippo, feeds her baby by literally dissolving her own body to make a white fluid that she secretes through her nipples. The ingredients of that fluid have been tweaked and perfected through 200 million years of evolution to provide all the nutrition that infants need. Those ingredients include complex sugars called oligosaccharides. Every mammal makes them but human mothers, for some reason, churn out an exceptional variety – scientists have identified over 200 human milk oligosaccharides, or HMOs, so far.32 They are the third-biggest part of human milk, after lactose and fats, and they should be a rich source of energy for growing babies.

Bifidobacteria

Bifidobacterium longum infantis,

As it digests HMOs, B. infantis releases short-chain fatty acids (SCFAs) that feed an infant’s gut cells – so while mothers nourish this microbe, the microbe in turn nourishes the baby. Through direct contact, B. infantis also encourages gut cells to make adhesive proteins that seal the gaps between them, and anti-inflammatory molecules that calibrate the immune system.

Human breast milk stands out among that of other mammals: it has five times as many types of HMO as cow’s milk, and several hundred times the quantity. Even chimp milk is impoverished compared to ours. No one knows why this difference exists, but Mills offers a couple of good guesses. One involves our brains, which are famously large for a primate of our size, and which grow incredibly quickly in our first year of life. This fast growth partly depends on a nutrient called sialic acid, which also happens to be one of the chemicals that B. infantis releases while it eats HMOs. It is possible that by keeping this bacterium well fed, mothers can raise brainier babies. This might explain why, among monkeys and apes, social species have more milk oligosaccharides than solitary ones, and a greater range of them to boot. Larger groups mean more social ties to remember, more friendships to manage, and more rivals to manipulate. Many scientists believe that these demands drove the evolution of primate intelligence; perhaps they also fuelled the diversity of HMOs. An alternative idea involves diseases. Pathogens can easily bounce from one host to another, so group-living animals need ways of protecting themselves against rampant infections. HMOs provide one such defence. When pathogens infect our guts, they almost always begin by latching onto glycans – sugar molecules – on the surface of our intestinal cells. But HMOs bear a striking resemblance to these intestinal glycans, so patho...

There is another way for hosts to reduce their conflict with their microbes, and it’s an extreme one: they can become so co-dependent that they effectively act as a single entity.42 This happens when bacteria find their way inside the cells of their hosts and are faithfully transmitted from parents to offspring. Their two parties’ fates are now entwined. They still have their own interests, but these overlap to such an extent that any remaining disagreements become negligible.

Take a globe and spin it until the side that faces you is largely blue. You are now staring into the Pacific Ocean, in all its daunting immensity. Now stab your finger into its heart. Down a bit. Right a bit. You are now prodding the Line Islands, a linear constellation of eleven tiny land masses, slashing their way through the middle of nowhere. Around 3,500 miles from California, 3,800 miles from Australia, and 4,900 miles from Japan, the Line Islands epitomise isolation. They are about as far away from anything else as you can get without leaving the planet. That is how far Forest Rohwer had to travel to find the most beautiful coral reefs he had ever seen.

Rohwer’s work with corals hints at a different type of microbial disease, one without a single obvious culprit.4 These illnesses are caused by communities of microbes, which have shifted into configurations that harm their hosts. None is a pathogen in its own right; instead, the entire community has shifted to a pathogenic state. There’s a word for such a state: dysbiosis.5 It is a term that evokes imbalance and discord in place of harmony and cooperation. It is the dark reflection of symbiosis, the antithesis of all the themes we have seen so far.

Akkermansia muciniphila,

Both major types of IBD – ulcerative colitis and Crohn’s disease – have been around for centuries, but rates have soared since World War II, especially in developed countries.

They do, however, point to a different culprit. Most of them are involved in producing mucus, solidifying the lining of the gut, or regulating the immune system – all things that keep microbes in line.

The IBD microbiome tends to be less diverse and less stable than its healthier counterparts. It lacks anti-inflammatory microbes, including fibre-fermenters like Faecalibacterium prausnitzii and B. fragilis. In their place are blooms of inflammatory species like Fusobacterium nucleatum and invasive strains of E. coli.

How did these communities come about? Was it something dietary that nourished inflammatory species? Antibiotics that killed off the anti-inflammatory ones? Genetic variants that altered the host’s immune system, disrupting its ability to manage its microbes? The last of these seems possible: Wendy Garrett has shown that mutant mice which lack important immune genes end up with unusual communities of gut microbes, and those communities can trigger signs of IBD when transplanted into healthy mice.

The best that anyone has been able to do is to show that microbes are already dysbiotic in people who have only recently been diagnosed.17 There is almost certainly no single trigger, microbial or otherwise, that causes IBD. It probably takes several hits to knock the ecosystem into an inflammatory state.

When babies emerge from the womb they are colonised by mum’s vaginal microbes – an endowment that creates chains of transmission which cascade through generations. This, too, is changing.

Maria Gloria Dominguez-Bello found that if babies are born through a cut in their mother’s abdomen, their starter microbes come from her skin and the hospital environment, instead of her vagina.

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

Bottle-feeding might exacerbate these problems. As we saw, breast milk engineers a baby’s ecosystem. It provides more microbe colonists for a baby’s gut, and HMOs – those microbe-feeding sugars in breast milk – that nourish co-adapted companions like B. infantis. These abilities might overwrite any initial differences caused by a C-section birth, but “if you go for a C-section and bottle-feeding, I’d certainly say that [your baby] is on a different trajectory,” says milk expert David Mills.

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.

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

Martin Blaser isn’t just worried that some people are short of important microbes. He is deeply concerned that some of these species may be disappearing altogether. Take Helicobacter pylori, his favourite bacterium. Blaser was partly responsible for ruining its reputation in the 1990s. Scientists already knew that it caused stomach ulcers, but he and others confirmed that it increases the risk of stomach cancer, too. Only later did he realise the microbe’s beneficial side: it reduces the risk of reflux (a condition where stomach acid gurgles back into the throat), oesophageal cancer, and perhaps asthma. Blaser now speaks about H. pylori with affection. It is one of the oldest of our old friends, having infected humans for at least 58,000 years.

Humans, you will be delighted to know, do not have pap. Our egg cells have no bacteria in them either (discounting mitochondria), and our mothers don’t cover us in mucus. Instead, we unite with our first microbes at the moment of birth.

In recent years, a few studies have challenged this concept by reporting traces of microbial DNA in supposedly sterile tissues like amniotic fluid, umbilical cord blood, and the placenta – but these results are highly controversial.12 It’s not clear how these microbes get there, whether their presence matters, or if they actually exist – the DNA could have come from dead cells, or from bacteria that contaminated the experiments. Tissier’s sterile womb hypothesis might be wrong, but it certainly hasn’t toppled yet.

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.

endosymbiosis