10% Human: How Your Body’s Microbes Hold the Key to Health and Happiness

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Although we have known for several decades that our bodies’ microbes offer us a few perks, like synthesising some essential vitamins, and breaking down tough plant fibres, the degree of interaction between our cells and theirs wasn’t realised until relatively recently. In the late 1990s, using the tools of molecular biology, microbiologists took a great leap into discovering more about our strange relationship with our microbiotas.

New DNA-sequencing technology can tell us which microbes are present, and allows us to place them within the tree of life. With each step down this hierarchy, from domain to kingdom then phylum through class, order and family, and on to genus, species and strain, individuals are more and more closely related to one another. Working from the bottom up, we humans (genus Homo and species sapiens) are great apes (family Hominidae), which sit alongside monkeys and others within the primates (order Primates). All of us primates belong with our fellow furry milk-drinkers, as a member of the mammals (class Mammalia), who then fit within a group containing animals with a spinal cord (phylum Chordata), and finally, amongst all animals, spinal cord or otherwise (think of our squid, for example), in kingdom Animalia, and domain Eukarya. Bacteria and other microbes (except the category-defying viruses) find their place on the other great branches of the tree of life, belonging not to kingdom Animalia, but to their own unique kingdoms in separate domains.

Sequencing allows different species to be identified and placed within the hierarchy of the tree of life. One particularly useful segment of DNA, the 16S rRNA gene, acts as a kind of barcode for bacteria, providing a quick ID without the need to sequence an entire bacterial genome. The more similar the codes of the 16S rRNA genes, the more closely related the species, and the more twigs and branches of the tree of life they share.

DNA sequencing, though, is not the only tool at our disposal when it comes to answering questions about our microbes, especially regarding what they do. For these mysteries, we often turn to mice. In particular, ‘germ-free’ mice. The first generations of these laboratory staples were born by Caesarean section and kept in isolation chambers, preventing them from ever becoming colonised with microbes, either beneficial or harmful ones. From then on, most germ-free mice are simply born in isolation to germ-free mothers, sustaining a sterile line of rodents untouched by microbes. Even their food and bedding is irradiated and packed in sterile containers to prevent any contamination of the mice. Transferring mice between their bubble-like cages is quite an operation, involving vacuums and antimicrobial chemicals.

By comparing germ-free mice with ‘conventional’ mice, which have their full complement of microbes, researchers are able to test the exact effects of having a microbiota. They can even colonise germ-free mice with a single species of bacterium, or a small set of species, to see precisely how each strain contributes to the biology of a mouse. From studying these ‘gnotobiotic’ (‘known life’) mice, we get an inkling of what microbes do in us as well. Of course, they are not the same as humans, and sometimes results of experiments in mice are wildly different from results in humans, but they are a fantastically useful research tool and very often provide crucial leads. Without rodent models, medical science would progress at a millionth of the speed.

It was by using germ-free mice that the commander-in-chief of microbiome science, Professor Jeffrey Gordon from the University of Washington in St Louis, Missouri, discovered a remarkable indication of just how fundamental the microbiota are to the running of a healthy body. He compared the guts of germ-free mice with those of conventional mice, and he learnt that under the direction of bacteria the mouse cells lining the gut wall were releasing a molecule that ‘fed’ the microbes, encouraging them to take up residence. The presence of a microbiota not only changes the chemistry of the gut, but also its morphology. The finger-like projections grow longer at the insistence of microbes, making the surface area large enough to capture the energy it needs from food. It’s been estimated that rats would need about 30 per cent more to eat if it weren’t for their microbes.

It is not only microbes that are benefiting from sharing our bodies, but us too. Our relationship with them is not just one of tolerance, but encouragement. This realisation, combined with the technical power of DNA sequencing and germ-free mouse studies, began a revolution in science. The Human Microbiome Project, run by the United States’ National Institutes for Health, alongside many other studies in laboratories around the world, has revealed that we utterly depend on our microbes for health and happiness.

The human body, both inside and out, forms a landscape of habitats as diverse as any on Earth. Just as our planet’s ecosystems are populated by different species of plants and animals, so the habitats of the human body host different communities of microbes. We are, like all animals, an elaborate tube. Food goes in at one end of the tube and comes out the other. We see our skin as covering our ‘outside’ surface, but the inner surface of our tube is also ‘outside’ – exposed to the environment in a similar way. Whilst the layers of our skin protect us from the elements, invading microbes and harmful substances, the cells of the digestive tract that runs right through us must also keep us safe. Our true ‘inside’ is not this digestive tract, but the tissues and organs, muscles and bones that are packed away between the inside and the outside of our tubular selves.

The surface of a human being, then, is not just their skin, but the twists and turns, furrows and folds of their inner tube as well. Even the lungs, the vagina and the urinary tract count as being on the outside – as part of the surface – when you view the body in this way. No matter if it’s inner or outer, all of this surface is potential real estate for microbes. Sites vary in their value, with dense city-like communities building up in resource-rich prime locations like the intestines, while sparser collections of species occupy more ‘rural’ or hostile locations such as the lungs and the stomach. The Human Microbiome Project set out to characterise these communities, by sampling microbes from eighteen sites across the inner and outer surfaces of the human body, in each of hundreds of volunteers.

Over the first five years of the HMP, molecular microbiologists oversaw a biotechnological echo of the golden age of species discovery; one that saw formaldehyde-infused collecting cabinets stuffed with the haul of birds and mammals discovered and named by explorer– biologists in the eighteenth and nineteenth centuries. The human body is, as it turns out, a treasure trove of strains and species new to science, many of them present on only one or two of the volunteers participating in the study. Far from each person harbouring a replicate set of microbes, very few strains of bacteria are common to everyone. Each of us contains communities of microbes as unique as our fingerprints.

Though the finer details of our inhabitants are specific to each of us, we all play host to similar microbes at the highest hierarchical levels. The bacteria living in your gut, for example, are more similar to the bacteria in the gut of the person sitting next to you, than they are to the bacteria on your knuckles. What’s more, despite our distinctive communities, the functions they perform are usually indistinguishable. What bacterium A does for you, bacterium B might do for your best friend.

From the arid, cool plains of the skin on the forearms to the warm, humid forests of the groin and the acidic, low-oxygen environment of the stomach, each part of the body offers a home to those microbes that can evolve to exploit it. Even within a habitat, distinct niches host different collections of species. The skin, all two square metres of it, contains as many ecosystems as the landscapes of the Americas, but in miniature. The occupants of the sebum-rich skin of the face and back are as different from those of the dry, exposed elbows as the tropical forests of Panama are from the rocks of the Grand Canyon. Where the face and back are dominated by species belonging to the genus Propionibacterium, which feed off the fats released by the densely packed pores in these areas, the elbows and forearms host a far more diverse community. Moist areas, including the navel, the underarms and the groin, are home to Corynebacterium and Staphylococcus species, which love the high humidity, and feed off the nitrogen in the sweat.

This microbial second skin provides a double layer of protection to the body’s true interior, reinforcing the sanctity of the barrier formed by the skin cells. Invading bacteria with malicious intentions struggle to get a foothold in these closely guarded bodily border towns, and face an onslaught of chemical weapons when they try. Perhaps even more vulnerable to invasion are the soft tissues of the mouth, which must resist colonisation by a flood of intruders smuggled on food and floating in the air.

From the mouths of their volunteers, researchers working on the Human Microbiome Project took not just one sample, but nine, each from a slightly different location. These nine sites turned out to have discernibly different communities, within mere centimetres of one another, made up of around 800 species of bacteria dominated by Streptococcus species and a handful of other groups. Streptococcus gets bad press, on account of the many species that cause diseases, from ‘strep throat’ to the flesh-eating infection necrotising fasciitis. But many other species in this genus behave themselves impeccably, crowding out nasty challengers in this vulnerable entrance to the body. Of course these tiny distances between sampling locations within the mouth may seem insignificant to us, but to microbes they are like vast plains and mountain ranges with climates as different as northern Scotland and the south of France.

Imagine, then, the climatic leap from the mouth to the nostrils. The viscous pool of saliva on a rugged bedrock replaced by a hairy forest of mucus and dust. The nostrils, as you might expect from their gatekeeper status at the entrance to the lungs, harbour a great range of bacterial groups, numbering around 900 species, including large colonies of Propionibacterium, Corynebacterium, Staphylococcus and Moraxella.

Heading down the throat towards the stomach sees the enormous diversity of species found in the mouth drop dramatically. The highly acidic stomach kills many of the microbes that enter with food, and just one species is known for certain to reside there permanently in some people – Helicobacter pylori, whose presence may be both a blessing and a curse. From this point on, the journey through the digestive tract reveals an ever-greater density – and diversity – of microbes. The stomach opens into the small intestine, where food is rapidly digested by our very own enzymes and absorbed into the bloodstream. There are still microbes here though; around ten thousand individuals in every millilitre of gut contents at the start of this 7-m-long tube, rising to an incredible ten million per millilitre at the end, where the small intestine meets the large intestine’s starting point.

Just outside the safe-house created by the appendix is a teeming metropolis of microbes, in the heart of the microbial landscape of the human body – the tennis-ball-like caecum, to which the appendix is attached. This is the epicentre of microbial life, where trillions of individual microbes of at least 4,000 species make the most of the partially digested food that has passed through round one of the nutrient-extraction process in the small intestine. The tough bits – plant fibres – are left over for the microbes to tackle in round two.

The colon, which forms most of the length of the large intestine, running up the right-hand side of your torso, across your body under your rib cage, and back down the left-hand side, provides homes for microbes, numbering one trillion (1,000,000,000,000) individuals per millilitre by now, in the folds and pits of its walls. Here, they pick up the scraps of our food and convert them into energy, leaving their waste products to be absorbed into the cells of the colon’s walls. Without the gut’s microbes, these colonic cells would wither and die – whilst most of the body’s cells are fed by sugar transported in the blood, the colonic cells’ main energy source is the waste products of the microbiota. The colon’s moist, warm, swamp-like environment, in parts completely devoid of oxygen, provides not only a source of incoming food for its inhabitants, but a nutrient-rich mucus layer, which can sustain the microbes in times of famine.

The human gut.

Because HMP researchers would have to cut open their volunteers to sample the different habitats of the gut, a far more practical way of collecting information about the gut’s inhabitants was to sequence the DNA of microbes found in the stool. On its passage through the gut, the food we eat is mostly digested and absorbed, both by us and our microbes, leaving only a small amount to come out the other end. Stool, far from being the remains of our food, is mostly bacteria, some dead, some alive. Around 75 per cent of the wet weight of faeces is bacteria; plant fibre makes up about 17 per cent.

At any one time, your gut contains about 1.5 kg of bacteria – that’s about the same weight as the liver – and the lifespans of individuals are a matter of just days or weeks. The 4,000 species of bacteria found in the stool tell us more about the human body than all the other sites put together. These bacteria become a signature of our health and dietary status, not only as a species, but as a society, and personally. By far the most common group of bacteria in the stool are the Bacteroides, but because our gut bacteria eat what we eat, bacterial communities in the gut vary from person to person.

The gut microbes aren’t just scavengers, though, taking advantage of our leftovers. We have exploited them too, especially when it comes to outsourcing functions that would take us time to evolve for ourselves. After all, why bother having a gene for a protein that makes Vitamin B12, which is essential for our brain function, when Klebsiella will do it for you? And who needs genes to shape the intestine’s walls, when Bacteroides have them? It’s much cheaper and easier than evolving them afresh. But, as we will discover, the role of the microbes living in the gut goes far beyond synthesising a few vitamins.

The Human Microbiome Project began by looking only at the microbiotas of healthy people. With this benchmark set down, the HMP went on to ask how they differ in poor health, whether our modern illnesses could be a consequence of those differences, and if so, what was causing the damage? Could skin conditions like acne, psoriasis and dermatitis signal disruption to the skin’s normal balance of microbes? Might inflammatory bowel disease, cancers of the digestive tract and even obesity be due to shifts in the communities of microbes living in the gut? And, most extraordinarily, could conditions that were apparently far removed from microbial epicentres, such as allergies, autoimmune diseases and even mental health conditions, be brought on by a damaged microbiota?

Lee Rowen’s educated guess in the sweepstake at Cold Spring Harbor hinted at a much deeper discovery. We are not alone, and our microbial passengers have played a far greater role in our humanity than we ever expected. As Professor Jeffrey Gordon puts it:

This perception of the microbial side of ourselves is giving us a new view of our individuality. A new sense of our connection to the microbial world. A sense of the legacy of our personal interactions with our family and environment early in life. It’s causing us to pause and consider that there might be another dimension to our human evolution.

We have come to depend on our microbes, and without them, we would be a mere fraction of our true selves. So what does it mean to be just 10 per cent human?