I Contain Multitudes: The Microbes Within Us and a Grander View of Life
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by Ed Yong
Read between December 29, 2017 - January 4, 2018
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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! Consider just one example: a common gut bacterium called Bacteroides fragilis or ‘B-frag’. In 2002, Sarkis Mazmanian showed that this particular microbe can fix some of the immune problems in germ-free mice. Specifically, its presence restores normal levels of ‘helper T cells’, a ...more
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From your perspective, choosing the right item on a menu is the difference between a good meal and a bad one. But for your gut bacteria, the choice is more important. Different microbes fare better on certain diets. Some are peerless at digesting plant fibres. Others thrive on fats. When you choose your meals, you are also choosing which bacteria get fed, and which get an advantage over their peers. But they don’t have to sit there and graciously await your decision. As we have seen, bacteria have ways of hacking into the nervous system. If they released dopamine, a chemical involved in ...more
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Bacteriocytes
Steve Mitchener
Found in insects they contain and control bacterial symbionts; stop them from spreading into other tissues; and hide them from the immune system.
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symbionts,
Steve Mitchener
An organism living with another symbiotically
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of our microbes live around our cells, not inside them. 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. Swarming within that tube are trillions of bacteria. There’s just one layer of epithelial cells – the ones that line our organs – stopping them from penetrating the walls of the gut and reaching the blood vessels that could carry them to other parts of the body.
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they too can control their symbionts. How? For a start, they use mucus, the same slimy goo that clogs your nose when you have a cold.
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Mucus is made from giant molecules called mucins, each consisting of a central protein backbone with thousands of sugar molecules branching off it. These sugars allow individual mucins to become entangled, forming a dense, nearly impenetrable thicket – a Great Wall of Mucus that stops wayward microbes from penetrating deeper into the body. And if that wasn’t deterrent enough, the wall is manned by viruses.
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When you think of viruses, you probably think of Ebola, HIV, or influenza: well-known villains that make us sick. But most viruses infect and kill microbes instead. These are called bacteriophages – literally, ‘eaters of bacteria’ – or phages, for short.
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Take the mammalian gut. The mucus that covers it comes in two layers: a dense inner one that sits directly on top of the epithelial cells, and a loose outer one beyond that. The outer layer is full of phages, but it’s also a place where microbes can anchor themselves and build thriving communities. They abound here. By comparison, very few of them exist in the dense inner layer. That’s because the epithelial cells liberally spray this zone with antimicrobial peptides (AMPs) – small molecular bullets that take out any encroaching microbes. They create what Lora Hooper calls a demilitarised ...more
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the gut’s immune system isn’t an undiscriminating barrier; it isn’t haphazardly mowing down any microbe that gets close. It is selective in its control.
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HMOs,
Steve Mitchener
scientists have identified over 200 human milk oligosaccharides, or HMOs
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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. But babies cannot digest them. When German first learned about HMOs, he was gobsmacked. Why would a mother spend so much energy manufacturing these complicated chemicals if they were indigestible and therefore useless to her child? Why hasn’t natural selection put its foot down on such a wasteful practice? Here’s a clue: these sugars pass through the stomach and the small intestine unharmed, and land in the large intestine where most of our bacteria live. So, ...more
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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.
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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.
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This is the price of symbiosis. Even when microbes aren’t as crucial to their hosts as a cicada’s symbionts are, they still exert a powerful influence on our lives and our health. When they go rogue, the consequences can be disastrous. That’s why humans and other animals have evolved so many ways of stabilising their multitudes. We restrict them by relying on the chemistry of our bodies. We corral them with physical barriers. We can go for the carrot, by nourishing them with dedicated foods. We can beat them with the stick, by using phages, antibodies, and other parts of our immune system. We ...more
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Think about microbial diseases. Think about influenza, AIDS, measles, Ebola, mumps, rabies, smallpox, tuberculosis, plague, cholera, and syphilis. All of these maladies, though different from each other, fit a similar pattern. They are caused by a single microbe: a virus or bacterium that infects our cells, reproduces at our expense, and triggers a predictable panoply of symptoms. This causal agent can be identified, isolated, and studied. With luck, it can be removed, ending the affliction. Rohwer’s work with corals hints at a different type of microbial disease, one without a single obvious ...more
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dysbiosis.
Steve Mitchener
is a term that evokes imbalance and discord in place of harmony and cooperation. It is the dark reflection of symbiosis,
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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.
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microbiome,
Steve Mitchener
A microbiota is an "ecological community of commensal, symbiotic and pathogenic microorganisms"[1][2] found in and on all multicellular organisms studied to date from plants to animals. A microbiota includes bacteria, archaea, protists, fungi and viruses. Microbiota have been found to be crucial for immunologic, hormonal and metabolic homeostasis of their host. The synonymous term microbiome describes either the collective genomes of the microorganisms that reside in an environmental niche or the microorganisms themselves
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the team showed that obese people (and mice) have different communities of microbes in their guts.10 The most obvious difference lay in the ratio of the two major groups of gut bacteria: obese people had more Firmicutes and fewer Bacteroidetes than their leaner counterparts. This raised an obvious question: does extra body fat tilt the Bacteroidetes/Firmicutes see-saw or, more tantalisingly, does the tilt make individuals fatter? The team couldn’t answer that question by relying on simple comparisons. They needed experiments.
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results showed that the guts of obese individuals contain altered microbiomes that can indeed cause obesity, at least in some contexts.
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the lean communities were inherently superior. Instead, Ridaura had tipped the battles in their favour by feeding her mice with plant-heavy chow. The complex fibres in these meals created many opportunities for microbes with the right digestive enzymes – ‘job openings for them to fill’, in Gordon’s words. The obese communities had few species that could fill those positions but the lean communities were brimming with qualified candidates, including fibre-busting specialists like B-theta. So, when obese communities colonised lean guts, they found that every morsel of food was already being ...more
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urbanisation: smaller families; a move from muddy countryside to concrete cities; a preference for chlorinated water and sanitised food; and a growing distance from livestock, pets and other animals. 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 ...more
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C-section babies are more likely to develop allergies, asthma, coeliac disease, and obesity later in life. ‘The baby’s immune system is naïve at birth and whatever it sees first will start its education,’
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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.
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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 ...more
Steve Mitchener
http://www.timeforwellness.org/blog-view/oatmeal-porridge-improves-gut-health-in-7days-558
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antibiotics are shock-and-awe weapons. They kill the bacteria we want as well as those we don’t – an approach that’s like nuking a city to deal with a rat.
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Much of modern medicine is built upon the foundations that antibiotics provide, and those foundations are now crumbling. We have used these drugs so indiscriminately that many bacteria have evolved to resist them, and some nigh-invincible strains can now shrug off every medicine we throw at them.36 At the same time, we have utterly failed to develop new drugs to replace the ones that are becoming obsolete. We are heading into a terrifying post-antibiotic era.
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microbes can have very different relationships with their hosts in different situations. H. pylori can be both hero and villain. Beneficial microbes can trigger debilitating immune responses if they bypass the mucus wall and penetrate the lining of the gut. Seemingly ‘unhealthy’ communities can be normal, even necessary.
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The Extended Phenotype, Richard Dawkins introduces the idea that an animal’s genes (its genotype) do more than sculpt its body (its phenotype). They also indirectly shape the animal’s environment. Beaver genes build beaver bodies, but since those bodies go on to make dams, the genes are also redirecting the flow of rivers. A bird’s genes create a bird, but they also make a nest. My genes made my eyes, hands, and brain, and in doing so they also made this book. All of these things – dams, nests, and books – are what Dawkins calls extended phenotypes. They are products of a creature’s genes that ...more
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holobiont,
Steve Mitchener
refers to a collection of organisms that spend significant parts of their lives together.
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made no sense to think of these collections of DNA separately. He believed that they work as a single entity – a holo- genome, which ‘should be considered as the unit of natural selection in evolution’.23 To understand what that means, remember that evolution by natural selection depends on just three things: individuals must vary; those variations must be heritable; and those variations must have the potential to affect their fitness – that is, their ability to survive and reproduce. Variation, inheritance, fitness: if all three boxes are ticked, the engine of evolution whirrs into action, ...more
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enzymes
Steve Mitchener
A substance, typically a protein, produced a living organism that acts as a catalyst to produce a specific biochemical reaction
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On land, life is powered by sunlight. Plants, algae, and some bacteria can harness the sun’s energy to make their own food, by refashioning carbon dioxide and water into sugars. This process, in which carbon is shunted from inorganic matter into edible substances, is called fixing carbon, and using the sun’s energy to do so is called photosynthesis.
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a different source of energy. For Riftia’s bacteria, that’s sulphur, or rather the sulphides that spew out of the vents. The bacteria oxidise these chemicals and use the liberated energy to fix carbon. This is chemosynthesis: making your own food using chemical energy instead of light or solar energy. And rather than producing oxygen as a waste product, as photosynthetic plants do, these chemosynthesising bacteria churn out pure sulphur.
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Dead whales, raining upon the ocean floor like manna from heaven, also create sulphide-rich environments that support temporary but teeming communities of chemosynthetic creatures.
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Life on Earth originated at deep-sea vents, and first took the form of chemosynthetic microbes. (Fittingly, one of the sites at the Galapagos Rift is called the Garden of Eden.) These ancestral microbes eventually evolved into endless forms most beautiful and most wonderful, spreading out of the depths and into the shallows. Some gave rise to more complex forms of life, like animals. And some of these, by partnering with chemosynthetic bacteria, managed to descend back into the abyss, to a world that would otherwise be too low in nutrients to support them. All the animals that live at ...more
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Plants are by far the most abundant source of food on land, but it takes more enzymatic power to digest them. Compared to animal flesh, plant tissues contain more complex carbohydrates, such as cellulose, hemicellulose, lignin, and resistant starches. Vertebrates don’t have the molecular chops for breaking these apart. Bacteria do. The common gut bacterium B-theta has over 250 carb-busting enzymes on its own; we have fewer than 100, despite owning a genome that’s 500 times bigger. By sundering plant carbohydrates with their broad toolkits, B-theta and other microbes release substances that ...more
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mammalian success was founded on vegetarianism, and that vegetarianism was founded on microbes. Time and again, different groups of mammals swallowed plant-breaking microbes from their environments, and used their enzymes to mount assaults on leaves, shoots, stems, and twigs. It’s not enough to have the right microbes. They need room and time to work. Plant-eating mammals gave them both. They enlarged parts of their guts into fermentation chambers, partly to house their digestive comrades and partly to slow the passage of food so they could do their thing. In elephants, horses, rhinos, ...more
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fatty acids
Steve Mitchener
Fatty acids are the building blocks of the fat in our bodies and in the food we eat. During digestion, the body breaks down fats into fatty acids, which can then be absorbed into the blood. Fatty acid molecules are usually joined together in groups of three, forming a molecule called a triglyceride. Triglycerides are also made in our bodies from the carbohydrates that we eat. Fatty acids have many important functions in the body, including energy storage. If glucose (a type of sugar) isn't available for energy, the body uses fatty acids to fuel the cells instead.
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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. One study asked ten volunteers to stick to two strict diets for five days each: one rich in fruit, vegetables, and grains, and the other heavy in meat, eggs, and cheese. As their diets changed, so did the recruits’ microbiomes – and quickly.
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our gut microbes make us more flexible eaters. That might not matter so much for people in developed countries, or zoo animals, both of whom are regularly and plentifully fed. But it could make all the difference to our hunter-gatherer ancestors,
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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.
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HGT is one of the most profound aspects of bacterial life. It allows bacteria to evolve at blistering speeds. When they face new challenges, they don’t have to wait for the right mutations to slowly amass within their existing DNA. They can just borrow adaptations wholesale, by picking up genes from bystanders that have already adapted to the challenges at hand. These genes often include dining sets for breaking down untapped sources of energy, shields that protect against antibiotics, or arsenals for infecting new hosts. If an innovative bacterium evolves one of these genetic tools, its ...more
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hologenome
Steve Mitchener
the sum of the genetic information of the host and its microbiota.
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We have already seen how pliable the microbiome can be. It can change with a touch, with a meal, with a parasitic incursion or a dose of medicine, or simply with the passage of time. It is a dynamic entity that waxes and wanes, forms and re-forms. This flexibility underlies many of the interactions between microbes and their hosts. It means that symbioses can change in positive ways, as new microbial partners offer fresh genes, abilities, and evolutionary opportunities to their hosts. It means that partnerships can change in negative ways, as dysbiotic communities or missing microbes lead to ...more
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healthcare relies on basic arithmetic. Got scurvy? You are missing vitamin C, which you can add to your body via fruit. Got flu? You have a virus, which you need to remove from your airways by taking a drug. Add what’s missing. Subtract what’s unwanted. These simple equations still drive much of modern medical thought. By contrast, the maths of the microbiome are more complicated, because they involve large, changing networks of connected, interacting parts. To control a microbiome is to sculpt an entire world – which is as hard as it sounds. Remember that communities have a natural ...more
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we need, then, are personalised infusions. We cannot expect the same probiotic strains, or the same donor stools, to treat a variety of diseases. A better approach would be to customise probiotics according to the ecological vacancies in an individual’s body, the quirks of their immune system, or the diseases that they are genetically vulnerable to.49 Doctors will also need to treat both the patient and their microbes at the same time.
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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 ...more
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vision is to engineer bacteria that can detect problems in the body – and fix them. Imagine a strain of E. coli that senses the signature molecules produced by Salmonella, and reacts by releasing antibiotics that specifically kill this microbe. Now, in addition to being a mere reporter, it’s also a park ranger. It could prevent food poisoning by patrolling the gut, staying inert if it sees no threat, and leaping into action if Salmonella appears. You could give it to children in poor countries, who are at risk of diarrhoeal diseases. You could give it to soldiers who deploy overseas. You could ...more
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