"I Contain Multitudes"

[fiefoe]

Ed Yong took us on a fantastic voyage that even surpasses the imaginative 1966 movie.

• But if our own cells were to mysteriously disappear, they would perhaps be detectable as a ghostly microbial shimmer, outlining a now-vanished animal core.
• Sometimes, if you look at a sponge under a microscope, you will barely be able to see the animal for the microbes that cover it. The even simpler placozoans are little more than oozing mats of cells;
• All of the concepts that ecologists use to describe the continental-scale ecosystems that we see through satellites also apply to ecosystems in our bodies that we peer at with microscopes. We can talk about the diversity of microbial species. We can draw food webs, where different organisms eat and feed each other. We can single out keystone microbes that exert a disproportionate influence on their environment
• All zoology is really ecology. We cannot fully understand the lives of animals without understanding our microbes and our symbioses with them.
• Before October, almost every living thing on the planet consisted of single cells. They would have been invisible to the naked eye, had eyes existed. They had been that way ever since life first emerged, some time in March.
• 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.
• As palaeontologist Andrew Knoll once said, “Animals might be evolution’s icing, but bacteria are really the cake.”
• 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.5 All eukaryotes descend from that fateful union. 。。 Other complex structures, from eyes to armour to many-celled bodies, have evolved on many independent occasions but the eukaryotic cell is a one-off innovation. That’s because, as Lane and others argue, the merger that created it – the one between an archaeon and a bacterium – was so breathtakingly improbable that it has never been duplicated, or at least never with success. By forging a union, those two microbes defied the odds and enabled the existence of all plants, animals,
• 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;
• Darwin certainly collected microbes – he called them “infusoria” – that blew onto the deck of the Beagle, and he corresponded with the leading microbiologists of the day.
• Hooke’s instruments magnified objects by 20 to 50 times; Leeuwehoek’s did so by up to 270 times. In their day they were easily the best microscopes on earth.
• Even though he was an amateur, the scientific method instinctively ran deep within him – as did a scientist’s untrammelled curiosity about the world. Through his lenses, he gazed at animal hairs, fly heads, wood, seeds, whale muscle, skin flakes, and ox eyes.
• A similar question could be asked of many people throughout the entire history of microbiome research: they were the ones who thought to look.
• 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). A century and a half would pass between the discovery of the microbial world and its earnest exploration.
• The narrative of disease and death still dominates our view of microbiology.
• In 1888, he found bacteria that pulled nitrogen out of the air and turned it into ammonia for plants to use; later, he isolated species that contributed to the movement of sulphur through the soil and atmosphere. This work stimulated a rebirth of microbiology in Beijerinck’s city of Delft –
• Many of these glitches can be rectified simply by giving the animals a normal complement of microbes or even isolated microbial molecules.6 The bacteria don’t physically reshape the gut themselves. Instead, they work via their hosts. They are more management than labour. 。。 In other words, the microbe told the mice how to use their own genes to make a healthy gut.
• 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.
• The traditional view of the immune system is full of military metaphors and antagonistic lingo. We see it as a defence force that discriminates self (our own cells) from non-self (microbes and everything else), and eradicates the latter. But now we see that microbes craft and tune our immune system in the first place!
• This result was the first time anyone had shown that a single microbe – no, a single microbial molecule – could correct a specific immune problem. 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.
• arguing that many mammals have bacteria in their scent glands, which ferment fats and proteins to produce smelly airborne molecules. Variations in these microbes could explain why different species have their own distinctive aromas
• Mazmanian had shown that gut microbes affect the immune system, and Patterson had found that the immune system affects the developing brain. And they realised that Patterson’s mice had gut problems in common with actual autistic children: both were more likely to have diarrhoea and other gastrointestinal disorders, and both harboured unusual communities of gut microbes.
• 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. We now know that gut microbes are part of this axis, in both directions.
• It was as dramatic a result as Collins could have hoped for: by swapping the bacteria in the animals’ guts, he had also swapped part of their personalities.
• 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. 。。 One recent study estimated that it infects at least four in every ten species of arthropods – the animal group that includes insects, spiders, scorpions, mites, woodlice, and more. That is a preposterous proportion! The majority of the 7.8 million or so living animal species are arthropods. If Wolbachia infects 40 per cent of them,3 it is arguably the most successful bacterium in the world, at least on land.
• Here is a strange but critical sentiment to introduce in a book about the benefits of living with microbes: there is no such thing as a “good microbe” or a “bad microbe”. These terms belong in children’s stories. They are ill-suited for describing the messy, fractious, contextual relationships of the natural world.6 In reality, bacteria exist along a continuum of lifestyles, between “bad” parasites and “good” mutualists.
• Others can change roles in the same hosts, depending on the context. All of this means that labels like mutualist, commensal, pathogen, or parasite don’t quite work as badges of fixed identity. These terms are more like states of being, like hungry or awake or alive, or behaviours like cooperating or fighting. They’re adjectives and verbs rather than nouns: they describe how two partners relate to one another at a given time and place.
• If the injury is severe, and enough mitochondria are released, the resulting body-wide inflammation can build into a lethal condition called systemic inflammatory response syndrome (SIRS).10 SIRS can be worse than the original injury. Absurdly, it’s simply the result of a human body mistakenly overreacting to microbes that have been domesticated for over two billion years.
• 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.”
• cooperation, found in textbooks and wildlife documentaries. And each of them is tinged with conflict, manipulation, and deceit.14 “We need to separate important from harmonious.
• All of us have found ways of stabilising our relationship with our microbes, of promoting fealty rather than defection. We have evolved ways of selecting which species live with us, restricting where they sit in our bodies, and controlling their behaviour so they are more likely to be mutualistic than pathogenic. Like all the best relationships, these ones take work. Every major transition in the history of life – from single-celled to multi-celled, from individuals to symbiotic collectives – has had to solve the same problem: how can the selfish interests of individuals be overcome to form cooperative groups? How, in other words, do I contain my multitudes?
• Cancer is a disease of cellular rebellion, where a cell strikes out against the regulations of its own body.
• But most viruses infect and kill microbes instead. These are called bacteriophages – literally, “eaters of bacteria” – or phages,
• Rohwer’s team member Jeremy Barr noticed that phages love mucus. In a typical environment, there will be 10 phages for every bacterial cell.23 In mucus, there will be 40. The same fourfold spike in phage concentrations exists in human gums, mouse guts, fish skins, marine worms, sea anemones, and corals.
• Rohwer suspects that phages were the original immune system – the means through which the simplest animals controlled the microbes at their door.
• 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.
• 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,.. So, what if they aren’t food for babies at all? What if they are food for microbes?
• It means that the measures by which we shape and control our microbiome – the phages, the mucus, the various arms of the immune system, and the ingredients in milk – are all connected. I’ve discussed them as if they were separate tools, but they are all part of a huge interwoven system for stabilising our relationships with our microbes.
• And breast milk? German was right: it’s far more than a bag of chemicals. It nourishes baby and bacteria, infant and infantis alike. It’s a preliminary immune system that thwarts more malevolent microbes. It is the means by which a mother ensures that her children have the right companions, from their first days of life.
• These interactions matter, because they foster stability. If a single bacterium was too efficient at harvesting glycans, it might eat away the mucus barrier itself, creating openings through which other microbes could enter. But if there are hundreds of competing species, they can all keep each other from gluttonously monopolising the food supply. By offering a wide array of nutrients we feed a wide range of microbes and stabilise our enormous, diverse communities.
• Instead, these corals are covered in dark algae and shrouded in especially turbid water. They are called black reefs. They are a marine vision of Tolkien’s Mordor, and they happen when a boatload of iron lands in an ecosystem that is generally poor in nutrients. The iron acts as fertiliser for fleshy algae, which grow so vigorously that even grazing fish can’t trim them back fast enough. The algae then trigger Rohwer’s cycle: more DOC, more microbes, more pathogens, more disease, more dead corals.
• 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.
• 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. It is disease, recast as an ecological problem. Healthy individuals are like virgin rainforests or lush grasslands or Kingman Reef.
• 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,
• 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.
• the microbiome is highly contextual... For example, gut microbiomes go through a huge upheaval by the third trimester of pregnancy and end up looking like those belonging to people with metabolic syndrome – a disorder that involves obesity, high blood sugar and a higher risk of diabetes and heart disease.
• 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.
• Woodlice can pick up microbes from their peers by cannibalising them. Mice can pick up bacteria from their neighbours by eating their droppings. Two bugs can pass microbes through their backwash if they both sip from the same plant. The average human swallows around a million microbes in every gram of food they eat.
• These acts of transmission, where animals hand microbes to their offspring in a generational relay, are among the most critical in the world of symbiosis, because they braid together the fates of hosts and symbionts.8 They ensure that the long waltz is actually long,
• Michael Lombardo. He argues that some animals came to live in large groups because they could more easily pick up beneficial symbionts from their neighbours.
• But there’s no “deeper into the body” for a hydra. It consists of just two layers of cells with a jelly-like filling, and so its outsides and insides are both in constant contact with water. It has no barrier to separate its tissues from its environment – no skin or shell, cuticles or coverings.
• Mitochondria certainly count: as we’ve seen, these cellular batteries were once free-living bacteria that became permanently enclosed within a larger cell. This process, known as endosymbiosis, was first proposed in the early twentieth century, but it only became accepted several decades later, largely thanks to the outspoken American biologist Lynn Margulis. She turned endosymbiosis into a coherent theory, which she expounded in a genre-hopping paper that contained an impressive mix of evidence from cell biology, microbiology, genetics, geology, paelaeontology, and ecology. It was a bravura piece of scholarship. It was also rejected around 15 times before seeing print in 1967.
• Lynn Margulis echoed his views in 2002, claiming that the creation of new symbioses between distinct organisms – which she called symbiogenesis – has been the main force behind the origin of new species. To her, the kinds of relationships you’ve seen so far in this book were not just pillars of evolution, but its very foundations.
• all animals evolved from single-celled predators that ate other things. Their food gave them many of the nutrients they needed, so they lost the genes for making these nutrients for themselves. We – that is, aphids, pangolins, humans, and the rest – are saddled with their legacy. None of us can make those ten essential amino acids, and we eat to fill the gap. And if we want to eat a specialised and impoverished diet like phloem sap, we need help. Enter bacteria. They have repeatedly allowed hemipterans to overcome a limitation that restrains the entire animal kingdom,
• Time and again, bacteria and other microbes have allowed animals to transcend their basic animalness and wheedle their way into ecological nooks and crannies that would be otherwise inaccessible; to settle into lifestyles that would be otherwise intolerable; to eat what they could not otherwise stomach; to succeed against their fundamental nature. And the most extreme examples of this mutually assured success can be found in the deep oceans, where some microbes supplement their hosts to such a degree that the animals can eat the most impoverished diets of all – nothing.
• The team were so unprepared to find life that there wasn’t a single biologist among them – they were all geologists. When they collected specimens and brought them back to the surface, the only preservative they had was vodka.
• Chemosynthesis explains why the worms are gutless and mouthless: their symbionts provide them with all the food they need. Unlike aphids or sharpshooters, which rely on bacteria for amino acids, these worms rely on their symbionts for everything.
• Shifting from meat to plants was an evolutionary breakthrough for our group. The sheer abundance and variety of plants allowed herbivores to diversify much faster than their carnivore kin, and spread into niches that had been vacated by the demise of the large dinosaurs. Today, the majority of living mammal species eat plants,
• This is exactly the world that bacteria live in. They can exchange DNA as easily as we might exchange phone numbers, money, or ideas. Sometimes, they sidle up to one another, create a physical link, and shuttle bits of DNA across: their equivalent of sex. They can also scrounge up discarded bits of DNA in their environment, left by their dead and decaying neighbours. They can even rely on viruses to move genes from one cell to another. DNA flows so freely between them that the genome of a typical bacterium is marbled with genes that arrived from its peers. ... Bacteria have been carrying out these horizontal gene transfers, or HGT for short, for billions of years,
• In the same way, animal bodies are hubs of genetic innovation, because they allow DNA to flow more freely between huddled masses of microbes. Close your eyes, and picture skeins of genes threading their way around your body, passed from one microbe to another. We are bustling marketplaces, where bacterial traders exchange their genetic wares.
• These stories portray HGT as an additive force, which infuses both microbes and animals with wondrous new powers. But it can also be subtractive. The same process that bestows useful microbial abilities upon animal recipients can make the microbes themselves wither and decay, to the point where they disappear entirely and only their genetic legacies remain.
• In the great evolutionary race, they sprint, while we crawl. But we can get a little closer to their blinding pace by forming partnerships with them. Bacteria, in other words, allow us to do decent impressions of bacteria.
• Even in this alliance, where either partner would die without the other, there is still conflict. And, in Taylor’s eyes, there is opportunity. He has been searching for drugs that kill Wolbachia, when it turns out that the nematodes have already evolved ways of doing exactly that. If A·WOL can find chemicals that stimulate their symbiont-control programmes, they could turn the simmering tensions between host and symbiont into outright war, cajoling the nematodes into launching the means of their own destruction.
• Yes, it is virulent. Yes, it represses the immune systems of amphibians. But it’s still just a fungus, and amphibians have been dealing with fungi for some 370 million years. This isn’t their first rodeo. They are fumbling this particular ride because they have already been weakened by changing climate, introduced predators, and environmental pollutants. Add a destructive and quickly spreading disease into the mix and the future suddenly looks exponentially bleak.
• Many doctors have tried to prevent NEC by giving probiotics to premature babies, with some success. But Underwood, after talking to people like Bruce German and David Mills, thinks that he can do better by infusing the infants with a combination of B. infantis and breast milk. “The food you feed these bugs is as important as the bugs themselves, in getting them to grow and colonise a fairly hostile environment,”