If I told you about a fellow creature that shares our food and habits, travels with us, has evolved with us to know what we like and dislike, and that we provide protection for, you might assume I was talking about your beloved dog or cat. In fact I’m talking about something a million times smaller and invisible to the naked eye.
Microbes are primitive forms of life that were the first inhabitants of earth, creatures that we generally ignored or took for granted. These creatures, too small to be seen with our eyes, we assumed to be mainly found in dirt and in or on other animals that didn’t wash. Yet our bodies contain 100 trillion of them, weighing over four pounds in our guts alone. Most of us know them intimately only from their associations with rare bouts of food poisoning – like salmonella in uncooked barbecue chicken or E. coli in an unwise late-night kebab. Apart from occasions like these, with all our ever-expanding knowledge and technology we assumed that these tiny and seemingly trivial beings couldn’t possibly influence our supremely powerful human bodies. We couldn’t have been more wrong.
Dancing animalcules
Spring, 1676: Anton Leeuwenhoek had overslept again and it was already light when he woke. There was noise and activity in the streets of Delft below. He had worked long into the night on his latest experiment and was still tired, but elated by his recent discoveries. Using his special home-made microscope, Anton had been looking at why chilli peppers are spicy, but by chance had stumbled across something even more revolutionary.
Anton was a draper by trade and was obsessively curious. Unlike most of his friends, he still had his own teeth and was fastidious about cleaning them daily, first by rubbing them vigorously with hard salt granules, then using a wooden toothpick, then rinsing, before polishing them with his special tooth cloth.
Today he took particular interest in examining with his fine magnifying mirror the whitish batter-like substance (nowadays known as plaque) that was coating his teeth. Anton had only a small amount of plaque compared to others he had examined, but even after he had cleaned his teeth it never seemed to have gone away completely. He scraped some off onto a glass slide, then added a few drops of fresh rainwater. Upon examining the slide Anton was amazed. There were tiny wriggly creatures everywhere. These ‘animalcules’, as he named them, were of all shapes and sizes – at least four distinct families of them, all ‘a-dancing prettily’. What shocked him was not their presence, but their abundance. ‘The number of these Animalcules in the scurf of a man’s teeth are so numerous that I believe they exceed the number of men in a kingdom,’ he wrote.
Anton Leeuwenhoek was perhaps the first man ever to see a microbe (by which we mean a living creature seen only by means of a microscope). He was certainly the first to describe them, and to realise that healthy humans are teeming with these creatures inside our guts and on our skin. He found them everywhere he looked, from our mouths to our food, from our drinking water to urine and stool samples. Despite this amazing discovery, unlike Newton and Galileo – scientists of the same era who explored outwards to the stars to achieve fame – he slid into relative anonymity.
You may not have given microbes much thought until now, perhaps because you can’t see them without the aid of a magnifying glass. Imagine how many grains of sand there are on earth – or, if you prefer, how many stars there are in the universe. Someone has actually counted the stars – well, made a very good estimate – and came up with a figure of 1024 (which is 1 + 24 zeros – an awful lot). If you multiply the estimate for all possible stars a million-fold you get a vast figure which, at 1030 (also called a ‘nonillion’), is the estimated number of bacteria on earth. If you are a gardener and by accident swallow a tiny fleck of earth it contains billions of bacterial cells, and a handful of earth contains more microbes than stars in the universe. You are no ‘safer’ swimming in the water, where a million bacterial cells are found in every millilitre of fresh or sea water. These microbes are the true and permanent inhabitants on earth; we humans are just passing through.
Microbes are present in most habitats – from the ordinary to the most extreme. Bacteria inhabit acidic hot springs, radioactive waste, and the deepest portions of the earth’s crust. Bacteria have even survived in space. We evolved not from Adam and Eve but from microbes, and we have continued our close connection with them ever since. This is most obvious in our guts, where thousands of diverse species that are as different from each other as we are from jellyfish play a much greater role than we ever realised.
Microbes generally get a bad press, but less than a tiny fraction of the millions of species are harmful to us and most, in fact, are crucial to our health. Microbes are not only essential to how we digest food, they control the calories we absorb and provide vital enzymes and vitamins as well as keeping our immune system healthy. Over millions of years we have evolved together with microbes for mutual survival, yet recently this fine-tuning and selection has gone wrong. Compared to our recent ancestors who lived outside cities, enjoying rich and varied diets and without antibiotics, we have only a fraction of the diversity of microbial species living in our guts. Scientists are only now starting to understand the long-lasting impact this has had on all of us.
Early colonists on virgin soil
Our personal encounter with microbes begins at birth. Within minutes of a healthy sterile baby’s delivery she will be swarming with microbes: millions of bacteria and even more viruses that feed off the bacteria, plus even a few fungi. Within hours she will be totally overrun with millions more.
Her head, eyes, mouth and ears are the first parts to be colonised as she passes along her mother’s soft vaginal wall, where many eager microbes in the moist and warm mucosal layer are waiting to make the leap. Then, because of their close proximity and the pressure on all of the body’s sphincters, a light mixture of urinary and faecal microbes are sprinkled onto her face and hands, followed by a different set of microbes covering the rest of her body as a result of rubbing against the skin of her mother’s legs. These tiny microbes are carried to the lips and mouth, usually from the baby’s own hands. They can’t usually get past the oceans of saliva sweeping them away, and if they do they face the harsh acid environment of the stomach and its juices, where most are destroyed.
At the first swallow of some alkaline breast milk (which acts like an antacid), a few lucky bacteria waiting either on the lips or mouth or on the mother’s nipple will be miraculously protected, and make it past the acid waterfall. These intrepid explorers can then start a whole new colony by reproducing wildly in the safety of the mucous layers of the baby’s intestine, and wait for more milk and other microbial companions to arrive. Even just a few colonists – if the conditions are right – by dividing every 40–60 minutes, can become trillions or billions of cells overnight.
Until the mid-1990s it was the dogma that most bodily fluids were sterile – that is, contained no microbes. When a team in Madrid claimed to have cultured dozens of microbes from healthy breast milk they were laughed at.1 Now we know that human milk contains hundreds of species, although we still don’t have a clue how they get there. We are no longer sure that any part of our bodies is completely devoid of microbes – even the womb and the eyeball – and they may even travel around our bodies unnoticed.2 When you next go to the toilet, spare a thought for your trillions of microbes. Nearly half the mass you are flushing away are microbes.
Although we are all born microbe-free, this state lasts just a few milliseconds. The process of microbe colonisation is not at all random and has been planned and finely tuned over millions of years. In fact both the microbes and the baby depend on each other for their survival and health. This delicate co-evolution between microbes and man has not left purely to chance the crucial planting of the first microbial seeds in the virgin soil. All mammals, and many other animals studied such as frogs, transmit their own carefully selected microbes to their babies in a process that is at least fifty million years old. This is how evolution has facilitated the leap of microbes from one generation to the next, and how our own unique community of microbes, called our microbiome, is established.
Diverse microbial gardens
We are surrounded by trillions of microbes in the dirt, dust, water and air that are not interested in colonising a newborn baby. They haven’t yet evolved the apparatus to be able to survive on or inside us and to derive enough energy to live. So the microbes that colonise humans are highly specialised, possessing pared-down genes to ensure there are no redundant or overlapping mechanisms with the human host. We humans share 38 per cent of our genes with the microbes inside us. As the transmission of microbes from mother to child is so universal in the animal kingdom, it is clearly crucial for our health.3
As soon as a woman gets pregnant the body readies itself for providing as much help as it can for the next generation via this special transmission of microbial genes. Inside the pregnant female the carefully programmed changes brought about by switching on genes in the body ensure that certain hormones modify metabolism and calorie intake while conserving energy, building up fat reserves in the breasts and buttocks, increasing glucose and stocking up breast milk. Other changes happen to the white cells controlling the immune system that must deal with the foreign object – the baby – inside her, without rejecting it. There are also changes to the microbes, anticipating the day when they will be transmitted to her baby in order to aid his or her growth and survival. These microbe changes are extremely powerful.
When researchers transplant the pregnant human mother’s stools into sterile mice, the mice get much fatter compared to those transplanted with non-pregnant human faeces.4 Experiments using these sterile, or germ-free, mice are a vital tool that we scientists use regularly in this area of research. They are carefully brought into the world via a sterile C-section in an oxygenated enclosure, avoiding contact with the other littermates or their mother or other microbes. They are then kept in sterile and isolated cages, fed sterile food, and observed. Without microbes they can survive, but only just. They definitely do not form the elite corps – they are puny, and don’t develop a normal brain, gut or immune system. Most significantly, they are expensive to feed as mice without microbes need a third more calories than normal mice to keep up their body weight – evidence of the vital importance of microbes in digesting food in the intestines.5
Most of our microbes inhabit our large intestine (the colon), which is the five-foot-long piece of gut before you get to the rectum and that absorbs most of the water. The piece of gut above it – the small intestine – is where most of our food and energy is absorbed into our blood system. Usually, food enters here having first been chopped up by our teeth, aided by the enzymes in our saliva and stomach. The small intestine also contains microbes, in smaller numbers, but we know much less about them and their precise roles. Food that needs more time to break down to release the nutrients gets sent on from here down to the large intestine filled with microbes.
If you give the sterile mice normal microbes after a few weeks they still never develop normally, but if they start life with gut microbes and you try to eradicate them with antibiotics (as humans sadly do all too often, with disastrous effects), although never healthy, they do much better.
Microbes predict obesity better than genes
Recent changes in our tiny gut microbes and to the community called our microbiome are likely to be responsible for much of our obesity epidemic, as well as its deadly consequences of diabetes, cancer and heart disease. Examining the DNA of the microbes in our guts gives us a much better predictor of how fat someone is compared to looking at all of our 20,000 genes. This predictive ability is likely to keep improving as we start to look at viruses and fungi as well. Subtle differences between the types of microbes that we host in our guts explain many of the links between our diets and health, and why the results of food research are so inconsistent between people and populations. For example, differences in our individual gut microbes can explain why a low-fat diet works for some people, while a high-fat diet is fine for some and dangerous for others; why some people can eat plenty of carbohydrates without problems and others extract more calories from the same amount and get fatter; why some eat red meat happily and others contract heart disease; or even why when old people move to care homes and their diets change, they often rapidly succumb to diseases.
The increasing promotion and use of restrictive diets that depend on just a few ingredients will inevitably lead to a further reduction in microbe diversity and eventually to ill health. Intermittent fasting (such as the Fast Diet or 5:2) may be the exception, as short-term fasting can stimulate friendly microbes, but this is only as long as the other, ‘free eating’, days contain a diverse diet. Fifteen thousand years ago our ancestors regularly ingested around 150 ingredients in a week. Most people nowadays consume fewer than twenty separate food items and many, if not most, of these are artificially refined. Most processed food products come depressingly from just four main ingredients: corn, soy, wheat or meat.
In 2012 I started the world’s then largest gut microbe study (Microbo-Twin), using the latest gene technology and five thousand twins to identify the microbes and their relation with diet and health. I subsequently launched the British Gut Project, which is a crowd-funded experiment linked to the American Gut Project that allows anyone with access to the internet and a postal service to test their own microbes and share the results with the world.6 I also experimented on myself with some diets and will share with you the exciting insights these bring to a new vision of nutrition. Only by understanding what makes our own personal microbes tick and interact with our bodies can we make sense of the total confusion of modern diets and nutrition and regain the correct balance of our ancestors.
A 2015 study of microbes in all the stations of the New York subway found they matched closely their previous hosts – the diverse population groups of the city, each with their own idiosyncrasies. The study also found that half the microbes it discovered were completely unknown.7 The good news is that although there is clearly still much to learn, we already know enough scientifically about our microbes and our bodies to enable us to alter our lifestyles, eating patterns and diets to suit our individual needs and improve our health.
It is useful to think of your microbial community as your own garden that you are responsible for. We need to make sure the soil (your intestines) that the plants (your microbes) grow in is healthy, containing plenty of nutrients; and to stop weeds or poisonous plants (toxic or disease microbes) taking over we need to cultivate the widest variety of different plants and seeds possible. I will give you a clue how we do this. Diversity is the key.