Читать книгу 10% Human: How Your Body’s Microbes Hold the Key to Health and Happiness - Alanna Collen, Alanna Collen - Страница 12

Garden warblers are the very epitome of the birder’s greatest identification challenge – the LBJ, or ‘Little Brown Job’. Their most distinguishing feature is, in fact, the absolute lack of any distinguishing features, making recognition of this small bird through a pair of shakily held binoculars particularly difficult. But boring birds these are not. Just a few months after hatching, juvenile garden warblers embark on a 4,000-mile migration from their summer homes across Europe to their winter residences in sub-Saharan Africa. It is a route they have never taken before, and they do it without the help of either their more experienced parents, or a map.

Before these tiny birds head off on this incredible journey, they prepare themselves for the effort of flying and the lack of food en route by becoming fat. Over just a couple of weeks, the warblers double in weight, going from a slender 17 g to a distinctly portly 37 g. In human terms, they become morbidly obese. On each day of the pre-migration binge, a garden warbler gains around 10 per cent of its original body weight – the equivalent of a 10-stone man putting on a stone a day until he weighs 22 stone. Then, once the birds are plump enough, they undertake a feat of endurance beyond the imagination of most elite athletes – flying thousands of miles with just a handful of meals along the way.

Of course, to become that fat that fast, the warblers must gorge themselves on summer’s bounty of food. Practically overnight, the birds shift from a diet of insects to one of berries and figs. Although the fruit is ripe enough to eat for several weeks before their binge begins, the warblers leave it untouched until the time is right. It’s as if a switch flips inside them, and suddenly they dedicate themselves to eating.

For a long time, researchers assumed that the weight gain in warblers and other migratory birds was simply the consequence of hyperphagia – excessive eating. But the incredible speed of the shift in these birds from lean to morbidly obese suggested there was something else going on to help them store so much fat. Something that had less to do with how much food they ate, and more to do with how that food was stored in their bodies. By keeping a check on how many extra calories the warblers ate, and how many calories came out in their droppings, researchers realised that the additional food the birds were consuming did not fully account for the weight they were managing to gain.

The riddle continues when it comes to the birds losing the excess weight again. Of course, as the obese warblers make their journey across the Mediterranean Sea and the Sahara Desert, their fat supplies dwindle. By the time they have arrived and settled in to their African winter home, they have returned to a normal warbler weight. But here’s the strange thing: captive garden warblers are no different. During the pre-migratory period at the end of summer, these caged birds still gain weight, becoming thoroughly obese in preparation for a journey they will never make. And, at the exact point that wild warblers arrive at their destination, the captive warblers completely shed their excess fat. Despite not flying 4,000 miles, and having unlimited access to food, these captive birds still lose the weight again when the migratory period is over.

It is quite extraordinary that warblers deprived of cues in the weather, day length and seasonal food supplies are still able to rapidly gain enormous stores of fat for the migratory period and then slim down again apparently effortlessly, perfectly in sync with their wild cousins. These are birds, with brains the size of a pea. They don’t gain weight, then think to themselves: ‘I really must go on a diet.’ They don’t fast, or exercise madly, either. Their food intake does relapse after the binge, but again, not enough to account for losing that much weight, that fast. Imagine being able to drop a stone a day for seven days – that’s the degree of weight loss these little birds manage once the migratory period is over. Even eating nothing at all would not result in that kind of weight loss in humans.

Although we don’t yet know exactly how this astounding degree of weight change is regulated in the warblers’ bodies, the fact that these shifts happen beyond what is expected from changes in caloric intake makes one thing clear: maintaining a stable weight is not always a simple case of balancing calories-in and calories-out. In humans, the scientifically accepted explanation for weight gain is this: ‘The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories expended.’

It seems obvious: if you eat too much and move too little, the extra energy must be stored and you will gain weight. And if you want to lose weight, you must eat less and move more. But the warblers are able to rapidly lay down fat reserves that appear to go far beyond the calories they eat, and then deplete those reserves far beyond the calories they burn. Clearly, there’s more to the weight-regulation game than meets the eye. If calories-in versus calories-out isn’t true for warblers, perhaps it’s not true for humans either?

Attempting to treat over 10,000 cases of obesity made the Indian physician Dr Nikhil Dhurandhar wonder the exact same thing. His patients returned again and again, after regaining the small amounts of weight they’d lost, or failing to lose any weight whatsoever. Despite the difficulties, Dhurandhar and his father – another doctor specialising in obesity – ran one of the most successful obesity clinics in Mumbai in the 1980s. But after a decade of trying to help people to eat less and move more, he began to feel his efforts – and those of his patients – were futile. ‘After weight loss, you gain weight again: that is the big problem. And that has been my frustration.’ Dhurandhar wanted to know more about mechanisms behind obesity. If eating less and moving more didn’t permanently cure obesity, perhaps eating more and moving less wasn’t the only cause.

It’s something we desperately need to work out. Our species is in the midst of a warbler-like collective weight gain. And just as in warblers, the amount of weight we have gained does not quite tally with changes in ‘calories consumed’ and ‘calories expended’. Even the biggest and most comprehensive of studies show that most of the weight we have gained as a species is not accounted for by the extra food we are eating, nor by our lack of physical activity. Some even indicate that we are eating less than we used to, and exercising just as much. The scientific debate about whether gluttony and sloth alone can fully account for the exponential rise in obesity over the past sixty years rumbles quietly on. It is a mere scientific undercurrent lapping at the foundations of research that’s seen as more relevant: which diets work best?

At the time of Dhurandhar’s frustrations, a mysterious disease was spreading through India’s chickens, killing the birds and destroying livelihoods. Dhurandhar’s family were friends with a veterinary scientist who was involved in looking for the cause and finding a cure. The culprit was a virus, he told Dhurandhar over dinner, and the birds would die with large livers, shrunken thymus glands and a lot of excess fat. Dhurandhar stopped him. ‘The dead chickens are especially fat?’ he checked. The vet confirmed it.

Dhurandhar was curious. Animals dying of a viral infection would normally be skinny, not fat. Was it possible that a virus could induce weight gain in chickens? Could this be the explanation behind his patients’ difficulties in losing weight? Dhurandhar, excited to know more, set up an experiment. He injected one group of chickens with the virus, and left another group alone. Sure enough, three weeks later, he found that the infected birds were far fatter than the healthy ones. It seemed as if the virus had made them gain weight as they fell ill. Could it be that Dhurandhar’s patients, and countless other humans around the world, were also infected with the virus?

What is happening to our species is on such an enormous and unprecedented scale, that in the distant future, when humanity looks back on the twentieth century, they’ll remember it not just for two world wars, nor solely for the invention of the internet, but as the age of obesity. Take a human body from 50,000 years ago and one from the 1950s, and they will look more similar to one another than either does to the average human body today. In just sixty years or so, our lean, muscular, hunter-gatherer-like physiques have been encased inside a layer of excess fat. It’s something that has never happened to humans on this scale before, and no other animal species – apart from the pets and livestock we care for – has succumbed to this anatomy-changing disease.

One in every three adults on Earth is overweight. One in nine is obese. That’s the average across all countries, including those where under-nutrition is more common than being overweight. Looking just at the figures for the fattest of countries is even harder to believe. On the South Pacific island of Nauru, for example, around 70 per cent of adults are obese, and a further 23 per cent are overweight. Just 10,000 people live in this tiny country, and only about 700 of them are a healthy weight. Nauru is officially the fattest nation on Earth, but it is closely followed by most of the other South Pacific islands and several Middle Eastern states.

In the West, we have gone from being skinny enough that no one thought to comment on, worry about, or count the number of overweight people, to being fat enough that it would be quicker to count those that remain skinny. Roughly two in three adults are overweight, and half of those are not just overweight, but obese. The United States, despite its reputation, is seventeenth in the world rankings, with a mere 71 per cent of the population overweight or obese. As for the UK, it ranks thirty-ninth, with 62 per cent of adults overweight (including 25 per cent obese): the highest figures in Western Europe. Even among children in the Western world, being too fat is shockingly common, with up to one-third of under-twenty-year-olds overweight – half of them obese.

Obesity has crept upon us in a way that makes it seem almost normal. Yes, there is a steady stream of articles and news pieces about the obesity ‘epidemic’ to remind us that it is actually a problem, but we have very quickly adapted to living in a society where most people are overweight. We are quick to assume that fatness is the next step along from greediness and laziness, but if that’s the case, it’s quite an indictment of human nature. Looking at our other achievements as a species over the past century or so – the inventions of mobile phones, the internet, aeroplanes, life-saving medicines and so on – suggests we are not all just lying around, stuffing ourselves with cake. The fact that lean people are now in the minority in the developed world, and that this change has happened in just fifty or sixty years, after thousands upon thousands of years of human leanness, is shocking – just what are we doing to ourselves?

On average, people in the Western world have gained roughly a fifth of their own body weight in the last fifty years alone. If your allotted time on Earth had fallen so that your ‘today’ fell in the 1960s, not the 2010s, you would, in all likelihood, be considerably lighter. People who are 11 stone in 2015 might well have been just over 9 stone in 1965, no special efforts required. Today, to regain a pre-1960s weight, tens of millions of people are perpetually on a diet, attempting to deprive themselves of foods for which their brains have a deep-rooted desire. But despite the billions of dollars spent on fad-dieting, gym-going and pill-taking, obesity levels rise inexorably.

This rise has taken place in the face of sixty years of scientific research into effective weight-maintenance and weight-loss strategies. In 1958, back when being overweight was still relatively rare, one of the pioneers of obesity research, Dr Albert Stunkard, said: ‘Most obese persons will not stay in treatment for obesity. Of those who stay in treatment, most will not lose weight. And of those who do lose weight, most will regain it.’ He was broadly right. Even half a century later, success rates in trials of weight-loss intervention strategies are extremely low. Often, less than half of participants achieve weight loss, and for most it’s just a few kilos over a year or more. Why is it so very hard?

Up to now, among those looking for explanations – and perhaps excuses – for their weight, genetics has been the fashionable place to lay the blame. Differences in human DNA, though, have not proved to be particularly illuminating when it comes to weight gain, with only a tiny proportion of our susceptibility to obesity explained by genes. In 2010, a huge study was conducted by a team of hundreds of scientists who hunted through the genes of a quarter of a million people in the hope of finding some that were associated with weight. Astonishingly, they discovered just 32 genes in our 21,000-strong genome that seemed to play a role in weight gain. The average difference in weight between people with the very lowest genetic likelihood of obesity and the very highest was just 8 kg (17 lb). For those who would like to blame their parents, that equates to between 1 per cent and 10 per cent extra risk of becoming overweight, and that’s for those people who are in possession of the worst combination of those gene variants.

Regardless of the genes involved, genetics could never be the full explanation for the obesity epidemic, because sixty years ago almost everyone was slim, despite having broadly the same gene variants as the human population today. What probably matters far more is the impact that a changing environment – our diets and lifestyles, for example – has on the workings of our genes.

Our other favourite explanation is that of a ‘slow metabolism’. ‘I don’t have to watch what I eat, I’ve got a quick metabolism,’ must be one of the most irritating comments a lean person can make, but it has no basis in science. A slow metabolism – or more correctly, a low basal metabolic rate – means that a person burns relatively little energy whilst doing absolutely nothing at all – no moving, no watching TV, no doing mental arithmetic. Metabolic rates do vary from person to person, but it is actually overweight people who have the faster metabolisms, not lean people. It simply takes more energy to run a big body than a small one.

So if genetics and low basal metabolic rates aren’t behind the obesity epidemic, and the amount we eat and move doesn’t fully explain our collective weight gain, what is the explanation? Like many people, Nikhil Dhurandhar wondered if there’s more to it than we assume. The possibility that a virus could be causing or exacerbating obesity in some people played on his mind. He tested fifty-two of his human patients in Mumbai for antibodies to the chicken virus – evidence that they had been infected by it at some stage. To his surprise, the ten most obese of these patients had had the virus at some point. Dhurandhar made up his mind; he would stop trying to treat obesity and start researching its causes instead.

We have reached the point in human history where we are considering, in the United Kingdom at least, that redesigning and re-routing the digestive system that evolution has given us is the best way to prevent us from eating ourselves to death. It seems that gastric bands and bypasses, which reduce the size of the stomach and prevent people from consuming everything that their brains and bodies tell them to, are the most effective and the cheapest way to get a grip on the obesity epidemic and its consequences for our collective health.

If diets and exercise are so futile that gastric bypasses are our only hope for significant weight loss, what does that say for the straightforward application of the laws of physics – energy intake minus energy burned equals energy stored – to us as animals governed by the laws of biochemistry?

As we are just beginning to learn, it’s not that simple. As the warblers and many hibernating mammals show, there’s more to managing weight than counting calories. Subscribing to a simple one-in, one-out system of balancing the body’s energy books utterly undermines the great complexities of nutrition, appetite regulation and energy storage. As George Bray, a doctor who has been researching obesity since the start of the epidemic, once said: ‘Obesity isn’t rocket science. It’s much more complicated.’

Two and a half thousand years ago, Hippocrates – the father of modern medicine – believed that all diseases begin in the gut. He knew little of the gut’s anatomy, let alone of the 100 trillion microbes that live there, but as we are learning two millennia later, Hippocrates was on to something. Back then, obesity was relatively uncommon, as was another twenty-first-century illness that clearly has its origins in the gut: irritable bowel syndrome. It’s with this most unpleasant of maladies that our microbes come into the picture.

In the first week of May 2000, unseasonably heavy rain drenched the rural town of Walkerton, Canada. As the rainstorms passed, Walkerton’s residents began to fall ill in their hundreds. With ever more people developing gastroenteritis and bloody diarrhoea, the authorities tested the water supply. They discovered what the water company had been keeping quiet for days: the town’s drinking water was contaminated with a deadly strain of E. coli.

It transpired that bosses at the water company had known for weeks that the chlorination system on one of the town’s wells was broken. During the rains, their negligence had meant that run-off from farmland had carried residues from manure straight into the water supply. A day after the contamination was revealed, three adults and a baby died from their illnesses. Over the next few weeks, three more people succumbed. In total, half of Walkerton’s 5,000-strong population were infected in just a couple of weeks

Even though the water supply was quickly cleaned and made safe to drink, the story didn’t end there for many of those that had fallen ill. The diarrhoea and cramps just kept coming. A full two years later, one-third of the people affected were still ill. They had developed post-infectious irritable bowel syndrome (IBS), and more than half of them still had it eight years after the outbreak.

As new IBS sufferers, these unfortunate Walkerton residents had joined the growing ranks of people in the West whose bowels rule their lives. For most with the condition, severe abdominal pain and unpredictable bouts of diarrhoea determine the freedom of their days. For others, it’s the opposite – constipation, and the pain that goes with it, lasting days and sometimes weeks at a time. ‘At least,’ says the British gastroenterologist Peter Whorwell of those with constipation-predominant IBS, ‘these patients can get out of the house.’ For a minority, the double difficulty of both diarrhoea and constipation makes daily life particularly unpredictable.

The trouble is, even though nearly one in five people in the West – mostly women – are stuck with this life-changing illness, we don’t actually know what it is. It’s not normal, that much is clear. The word ‘irritable’ belies the impact that IBS has on the lives of its sufferers; the disease is consistently ranked as reducing quality of life even more than for patients on kidney dialysis and diabetics reliant on insulin injections. Perhaps it’s the hopelessness that comes with not knowing what’s wrong, nor how to fix it.

The spread of IBS is an unremarked global pandemic. One in ten visits to the doctor relate to the condition, and gastroenterologists are kept in a job by the steady flow of sufferers who make up half of their patients. In the United States, IBS leads to 3 million visits to the doctor, 2.2 million prescriptions, and 100,000 hospital visits each year. But we keep it quiet. No one wants to talk about diarrhoea.

The cause, however, remains elusive. Whereas the colon of a person suffering from inflammatory bowel disease would be coated with ulcers, the intestines of people with IBS appear as pink and smooth as those of a healthy person. This lack of physical signs has led to IBS becoming tainted by the historical assumption that it is all in the mind. Though for most sufferers their IBS is at its worst when they are stressed, it’s unlikely that stress alone is the sole cause of such a persistent illness. The staggering proportion of people with IBS deserves an explanation – we haven’t been through millions of years of evolution just to need to be within thirty seconds of a loo.

A clue is to be found in the Walkerton tragedy. The people stuck with IBS after the water-contamination incident are not the only IBS sufferers to blame their illness on a gastrointestinal infection of some kind. Around a third of patients pinpoint the moment their gut troubles started on an episode of food poisoning or similar, which never seemed to resolve. Traveller’s diarrhoea is often the beginning – people who pick up a bug abroad are up to seven times more likely to get IBS. But testing for the original bug yields nothing – they are no longer suffering from the gastroenteritis itself. It’s as if the original infection has thrown the gut’s normal residents into disarray.

For others, the onset of their IBS coincides not with an infection, but with a course of antibiotics. Diarrhoea is a common side effect of taking certain antibiotics, and for some patients it continues long after all the pills have been popped. There’s a paradox though, as antibiotics can also be used to treat IBS, apparently staving off the problem for weeks or months at a time.

So what’s going on? These clues – the gastroenteritis and the antibiotics – hint at a common theme: that short-term disruption of the gut’s microbes can have long-lasting effects on the microbiota’s composition. Imagine a virgin rainforest, verdant and dense with life: insects rule the undergrowth and primates hoot from the canopy. Now see the loggers move in, chainsawing the forest’s leafy infrastructure, established over millennia, and bulldozing the rest. Imagine too a weed invading, perhaps having hitchhiked as a seed on the wheels of the diggers, and then crowding out the natives as it takes hold. The forest will regrow, given time, but it will not be the same pristine, complex, unspoilt habitat it was before. Diversity will drop. Sensitive species will die out. Invaders will flourish.

For the complex ecosystem of the gut, on a scale a million times tinier, the principle still stands. Antibiotic chainsaws and invasive pathogens pull apart the web of life that’s forged a balance through countless subtle interactions. If the destruction is large enough, the system cannot bounce back. Instead, it collapses. In the rainforest, this is habitat destruction. In the body, it causes dysbiosis – an unhealthy balance of microbiota.

Antibiotics and infections are not the only causes of dysbiosis. An unhealthy diet or a nasty medication might have the same effect, throwing off the healthy balance of microbial species and reducing their diversity. It is this dysbiosis, in whatever form it takes, that sits at the heart of twenty-first-century illnesses, both those that start – and end – in the gut, like IBS, and those that affect organs and systems all around the body.

In IBS, the impact of antibiotics and gastroenteritis suggests that the chronic diarrhoea and constipation might be rooted in gut dysbiosis. You can detect what species are living in people’s guts and what their abundances are using DNA sequencing. Doing that with people with IBS and healthy people shows that most people with IBS have distinctly different microbiotas than people without it. Some IBS patients, though, have microbiotas that are no different from those of healthy people. These patients tend to report being depressed, suggesting that for a small subset of IBS sufferers, psychological illness drives the IBS, whereas for others, dysbiosis is the primary cause, and stress simply worsens it.

Amongst IBS sufferers with dysbiosis, some research has found differences in the composition of their microbiotas according to the type of IBS they have. Patients who complained of being bloated and feeling full quickly when eating had higher levels of Cyanobacteria, whereas those who suffered a lot of pain had a greater quantity of Proteobacteria. For constipated patients, a whole community of seventeen bacterial groups were present in the gut in increased numbers. Other studies have found that not only is an altered microbiota present, but it is highly unstable compared with that of healthy people, with different groups of bacteria waxing and waning over time.

In retrospect, it might seem predictable that irritable bowel syndrome is likely to be a consequence of bowels ‘irritated’ by the ‘wrong’ microbes. As a logical extension it is highly plausible: from a quick bout of diarrhoea brought on by bacteria in dirty water or undercooked chicken, to chronic bowel dysfunction, all because the gut’s bacteria have got out of balance. But whereas a diarrhoeal illness can often be blamed on a particular pathogenic bacterium – for example, Campylobacter jejuni in the case of food poisoning from raw chicken – IBS can’t be pinned on one nasty bug. Instead, it seems to be something about the relative numbers of what are normally seen as ‘friendly bacteria’. Perhaps not enough of one variety, or too many of another. Or even a species that behaves itself under normal circumstances but turns nasty given a chance to take over.

If the gut community found in IBS patients has no overtly infectious player, how exactly does dysbiosis wreak such havoc with the functioning of the gut? The groups of bacteria present in the gut of a person with IBS also seem to be present in the gut of a healthy person, so how can changes in their numbers alone be responsible? At the moment, this is proving a difficult question for medical scientists to answer, but studies have revealed some interesting clues. Although IBS sufferers do not have ulcers on the surface of their intestines as in inflammatory bowel disease, their guts are more inflamed than they should be. It’s likely the body is attempting to flush the microbes out of the gut, by opening tiny gaps between the cells lining the gut wall and allowing water to rush in.

It’s easy to imagine how having the wrong balance of microbes in the gut could cause IBS. But what about gut trouble of a different kind – the expansion of the human waistline? Could the microbiota be the missing link between calories-in and calories-out?

Sweden is a country that takes obesity very seriously. Although ranked as only the ninetieth-fattest country on the planet, and one of the slimmest in Europe, Sweden has the highest rate of gastric bypass surgeries in the world. The Swedish have considered implementing a ‘fat tax’ on high-calorie foods, and doctors are able to prescribe exercise to overweight patients. Sweden is also home to a man who has made one of the biggest contributions to forwarding obesity science since the epidemic began.

Fredrik Bäckhed is a professor of microbiology at Gothenburg University, although it’s not Petri dishes and microscopes you’ll find in his lab, but dozens of mice. Like humans, mice play host to an impressive collection of microbes, mainly living in their guts. But Bäckhed’s mice are different. Born by Caesarean section and then housed in sterile chambers, they do not have any microbes in them. Each one is a blank canvas – ‘germ-free’, which means that Bäckhed’s team can colonise them with whichever microbes they wish.

Back in 2004, Bäckhed took a job with the world’s leading expert on the microbiota, Jeffrey Gordon, a professor at Washington University in St Louis, Missouri. Gordon had noticed that his germ-free mice were particularly skinny, and he and Bäckhed wondered if this was because they lacked gut microbes. Together, they realised that even the most basic studies on what microbes did to an animal’s metabolism had not yet been done. So Bäckhed’s first question was simple: Do gut microbes make mice gain weight?

To answer that question, Bäckhed reared some germ-free mice to adulthood, and then dotted their fur with the contents of the caecum – the chamber-like first part of the large intestine – of mice who had been born normally. Once the germ-free mice had licked the caecal material off their fur, their guts took on a set of microbes like any other mouse. Then something extraordinary happened: they gained weight. Not just a little bit, but a 60 per cent increase in body weight in fourteen days. And they were eating less.

It seemed it wasn’t only the microbes that were benefiting from being given a home inside the mice’s guts, but the mice as well. Everybody knew that microbes living in the gut were eating the indigestible parts of the diet, but no one had ever looked into how much this second round of digestion contributed to energy intake. With microbes helping them to access more of the calories in their diets, the mice could get by on less food. In terms of our understanding of nutrition, it really rocked the boat. If the microbiota determined how many calories mice could extract from their food, did that mean they might be involved in obesity?

Microbiologist Ruth Ley – another member of Jeffrey Gordon’s lab group – wondered if the microbes in obese animals might be different to those in lean animals. To find out, she used a genetically obese breed of mice known as ob/ob. At three times the weight of a normal mouse, these obese mice look nearly spherical, and they just will not stop eating. Although they appear to be a completely different species of mouse, they actually have just a single mutation in their DNA that makes them eat non-stop and become profoundly fat. The mutation is in the gene that makes leptin, a hormone which dampens the appetite of both mice and men if they have a decent supply of stored fat. Without leptin informing their brains that they are well-fed, the ob/ob mice are literally insatiable.

By decoding the DNA sequences of the barcode-like 16S rRNA gene of the bacteria living in the guts of the ob/ob mice, and working out which species were present, Ley was able to compare the microbiotas of obese and lean mice. In both types of mice, two groups of bacteria were dominant: the Bacteroidetes and the Firmicutes. But in the obese mice, there was half the abundance of Bacteroidetes than in the lean mice, and the Firmicutes were making up the numbers.

Ley, excited by the possibility that this difference in the ratio of Firmicutes to Bacteroidetes might prove to be fundamental to obesity, then checked the microbiotas of lean and obese humans. She found the same ratio – the obese people had far more Firmicutes and the lean people had a greater proportion of Bacteroidetes. It seemed almost too simple – could obesity and the composition of the gut microbiota be connected in such a straightforward way? Most importantly, were the microbes in obese mice and humans causing the obesity, or were they just a consequence of it?

It fell to a third member of Gordon’s lab group to find out – PhD student Peter Turnbaugh. Turnbaugh used the same kind of genetically obese mice as Ley had, but he transferred their microbes into germ-free mice. At the same time, he transferred the microbes of normal, lean mice into a second set of germ-free mice. Both sets of mice were given exactly the same amount of food, but fourteen days later, the mice colonised with the ‘obese’ microbiota had got fat, and those with the ‘lean’ microbiota had not.

Turnbaugh’s experiment showed not only that gut microbes could make mice fat, but also that they could be passed between individuals. The implications go far beyond moving bacteria from obese mouse to lean mouse. We could be doing it the other way round – taking microbes from lean people and putting them into obese people – weight loss with no dieting required. The therapeutic – and money-making – potential was not lost on Turnbaugh or his collaborators, who have patented the concept of altering the microbiota as a treatment for obesity.

But before we get too excited about the potential for a cure for obesity, we need to know how it all works. What are these microbes doing that makes us fat? Just as before, the microbiotas in Turnbaugh’s obese mice contained more Firmicutes and fewer Bacteroidetes, and they somehow seemed to enable the mice to extract more energy from their food. This detail undermines one of the core tenets of the obesity equation. Counting ‘calories-in’ is not as simple as keeping track of what a person eats. More accurately, it is the energy content of what a person absorbs. Turnbaugh calculated that the mice with the obese microbiota were collecting 2 per cent more calories from their food. For every 100 calories the lean mice extracted, the obese mice squeezed out 102.

Not much, perhaps, but over the course of a year or more, it adds up. Let’s take a woman of average height, 5 foot 4 inches, who weighs 62 kg (9 st 11 lb) and has a healthy Body Mass Index (BMI: weight (kg) /(height (m)²) of 23.5. She consumes 2,000 calories per day, but with an ‘obese’ microbiota, her extra 2 per cent calorie extraction adds 40 more calories each day. Without expending extra energy, those further 40 calories per day should translate, in theory at least, to a 1.9 kg weight gain over a year. In ten years, that’s 19 kg, taking her weight to 81 kg (12 st 11 lb) and her BMI to an obese 30.7. All because of just 2 per cent extra calories extracted from her food by her gut bacteria.

Turnbaugh’s experiment has set in motion a revolution in our understanding of human nutrition. The calorie contents of foods are normally calculated using standard conversion tables, so every gram of carbohydrate is deemed to contribute 4 calories, every gram of fat, 9 calories, and so on. These labels present the calories of a food item as a fixed value. They are saying: ‘This yogurt contains 137 calories’, and ‘A slice of this bread contains 69 calories.’ However, Peter Turnbaugh’s work suggests it is not that straightforward. That yogurt may well contain 137 calories for a person of normal weight, but it could also contain 140 calories for someone who is overweight, and who has a different set of gut microbes. Again, it’s a small difference, but it adds up.

If your microbes are working on your behalf to extract energy from your food, it is your particular community of microbes that determines how many calories you get from what you eat, not a standard conversion table. For those people who have dieted without success, this may be part of the explanation. A carefully calculated calorie-controlled diet, resulting in an overall loss of calories every day for a sustained period, should lead to weight loss. But if the ‘calories-in’ are underestimated, that could mean no change in weight, or even weight gain. This idea is backed up by another experiment carried out by Reiner Jumpertz in 2011 at the National Institute of Health in Phoenix, Arizona. Jumpertz gave human volunteers a fixed-calorie diet, and simply measured the calories that remained in their stool after digestion. Lean volunteers put on a high-calorie diet had a boost in the abundance of Firmicutes relative to Bacteroidetes. This change in gut microbes went along with a drop in the number of calories that were coming out in their stool. With the balance of bacteria shifted, they were extracting an extra 150 calories each day from the same diet.

The particular set of microbes we harbour determines our ability to extract energy from our food. After the small intestine has digested and absorbed as much as it can from what we’ve eaten, the leftovers move into the large intestine, where most of our microbes live. Here, they function like factory workers, each breaking down its own preferred molecules and absorbing what it can. The rest is left in a simple enough form for us to absorb through the lining of the large intestine. One strain of bacteria might have the genes needed to break down the amino-acid molecules that come from meat. Another strain might be best suited to breaking down the long-chain carbohydrate molecules that come from green vegetables. And a third could be most efficient at collecting up the sugar molecules that were not absorbed in the small intestine. The diet each of us eats affects which strains we harbour. So, for example, a vegetarian might not have many individuals of the amino-acid strain, as they can’t proliferate without a steady supply of meat.

Bäckhed suggests that what we can extract from our food depends on what our microbial factory has been set up to expect. If our vegetarian were to abandon her stance and indulge in a hog roast, she would probably not have enough amino-acid-loving microbes to make the most of it. But a regular meat-eater would have a sizeable collection of suitable microbes, and would extract more calories from the hog roast than the vegetarian. And so it follows for other nutrients. A person who eats very little fat would have very few microbes that are specialised for fat, and the odd doughnut or chocolate bar might make it through the large intestine without being efficiently stripped of its remaining calorific content. Someone who eats a daily tea-time treat, however, would have a large population of fat-munching bacteria, just waiting to strip their next doughnut to its bare essentials, providing our snacker with the full dose of calories.

Although the number of calories we absorb from our food is undoubtedly important, it’s not just how much energy our microbes extract for us that matters, but what they make the body do with that energy. Do we use it immediately to power our muscles and our organs? Or do we store it for later, in case there’s nothing to eat? Which of these things happens depends on our genes. But it’s not which gene variants you got from your parents that matters, it’s which genes are switched on and which are switched off, which are dialled up and which are dialled down.

Our own bodies do the turning on and off of genes, and the dialling up and down, using all sorts of chemical messengers. This control means that cells in our eyes can do different jobs than cells in our livers, for example. Or that cells in the brain can function differently when we’re working during the day than when we’re sound asleep in the middle of the night. But our bodies are not the only masters of our genetic output. Our microbes also get a say, controlling some of our genes to suit their needs.

Members of the microbiota are able to turn up production from genes which encourage energy to be packed away in our fat cells. And why not? The microbiota benefits from living in a human who can make it through the winter just as much as the human does. An ‘obese microbiota’ turns up these genes even more, forcing the storage of extra energy from our food as fat. Annoying as this may be for those of us who struggle to maintain the weight they’d like, this gene-control trick should be beneficial, as it helps us to make the most of our food and store that energy away for leaner times. In our past, in periods of feast and famine, having help to get through the famines would have been a life-saver.

Calories-in, then, goes deeper than what you put in your mouth. It’s what your gut absorbs, including what your microbes provide for you. Calories-out, too, is more complicated than how much energy you use being active. It’s also about what your body chooses to do with that energy: whether it stores it away for a rainy day, or burns it off immediately. Although both of these mechanisms show how one person might absorb and store more than another, depending on the microbes they host, it raises another question: why don’t people who absorb more energy and store more fat simply feel satiated sooner? Why, if they have absorbed plenty of calories, and stored plenty of fat, are some people driven to keep on eating?

Your appetite is governed by many things, from the immediate, physical sensation of a full stomach to hormones that tell the brain how much energy is stored as fat. The chemical I mentioned earlier that was missing in the genetically obese mice – leptin – is one such hormone. It is produced directly by fat tissue, so the more fat cells we have, the more leptin gets released into the blood. It’s a great system – it tells the brain we’re satiated once we have accumulated a healthy amount of stored fat, and our appetites are suppressed.

So why don’t people lose interest in food once they start to put on weight? When leptin was discovered in the 1990s, courtesy of the ob/ob mice who were genetically unable to make leptin of their own, there was a flurry of excitement about using the hormone to treat patients with obesity. Injecting ob/ob mice with it led to very rapid loss – they ate less, they moved around more, and they dropped to nearly half of their body weight in a month. Even giving leptin to normal, lean mice made them lose weight. If mice could be treated this way, could leptin be the cure for human obesity?

The answer, as is obvious from the continuing obesity epidemic, was no. Giving obese people leptin injections had hardly any effect on their weight or their appetites. Though disappointing, this failure shed light on the true nature of obesity. Unlike in the ob/ob mice, it is not too little leptin that allows people to become fat. In fact, overweight people have particularly high levels of leptin, because they have extra fat tissue that produces it. The trouble is, their brains have become resistant to its effects. In a lean person, gaining a bit of weight leads to extra leptin production, and a decrease in appetite. But in an obese person, though plenty of leptin is being produced, the brain can’t detect it and so they never feel full.

This leptin resistance hints at something important. In obesity, normal mechanisms of appetite regulation and energy storage have fundamentally changed. Excess fat is not just a place to pack away unburnt calories, it’s an energy-usage control centre, a bit like a thermostat. When the body’s fat cells are comfortably full, the thermostat clicks off, reducing appetite and preventing further food intake from being stored. Then as fat stores fall low, the thermostat clicks back on again, increasing appetite and storing more food as fat. As in the garden warblers, weight gain is not just about eating more, it’s about biochemical shifts in how the body manages energy. This ‘warbler effect’ undermines the basic assumption that balancing what we eat with how much we move is all that’s necessary to maintain a stable weight. If this belief is wrong, perhaps obesity is not a straightforward ‘lifestyle disease’, born of gluttony and sloth, but an illness with an organic origin beyond our control.

If this seems like too radical a suggestion, consider this: just a few decades ago, stomach ulcers were ‘known’ to be caused by stress and caffeine. Like obesity, they were thought of as a lifestyle disease – change your habits and the problem will go away. The solution was simple: keep calm and drink water. But this treatment didn’t work – patients returned again and again, with acid burning holes in their stomachs. The cause of their failure to recover was deemed obvious; these patients must not be sticking to their treatment plans, allowing stress to prevent them from getting better.

But then, in 1982, two Australian scientists, Robin Warren and Barry Marshall, discovered the truth. A bacterium called Helicobacter pylori that sometimes colonised the stomach was causing ulcers and the related condition gastritis. Stress and caffeine simply made them more painful. Such was the resistance of the scientific community to Warren and Marshall’s idea, that Marshall drank a solution of H. pylori, giving himself gastritis in the process, to prove the connection. It took fifteen years for the medical community to fully embrace this new cause. Now, antibiotics are a cheap and effective way to cure ulcers for good. In 2005, Warren and Marshall won a Nobel Prize in Physiology or Medicine for their discovery that stomach ulcers were not a lifestyle disease, as dogma dictated, but the result of an infection.

Likewise, with his virus, Nikhil Dhurandhar was challenging the dogma that obesity was a lifestyle disease – one of excess. To investigate the possibility that a viral infection could be capable of causing weight gain in humans, he needed to switch from practising medicine to researching the science behind it. Dhurandhar decided to uproot his family and move to the United States, in the hope of getting the research funding he would need to find answers to his questions. It was a leap of faith, in the face of stiff opposition from the scientific establishment. But it would eventually pay off.

Two years after he had moved to America, Dhurandhar had still not managed to convince anyone to support his research into the chicken virus. He was on the brink of giving up and returning to India when the nutritional scientist Professor Richard Atkinson, at the University of Wisconsin, agreed to give him a job. At last, Dhurandhar was ready to begin his experiments. But there was a major obstacle: the American authorities refused them permission to import the chicken virus into the United States – it might cause obesity, after all.

Together, Atkinson and Dhurandhar devised a new plan. They would study another virus – this time one that was common in Americans – in the hope that it too might be responsible for weight gain. Based on a hunch that it was similar to the chicken virus, they selected a different virus that was known to cause respiratory infections from a laboratory catalogue, and ordered it through the post. Its name was Adenovirus 36, or Ad-36.

Once again, Dhurandhar began his experiments with a group of chickens. He infected half the birds with Ad-36 and the other half with a different adenovirus, more normally found in birds. And then he and Atkinson waited. Would Ad-36 make the birds fat, just as the Indian virus had done?

If it did, Dhurandhar would be making a big claim. He would be suggesting that overeating and being under-active were not the sole cause of human obesity; that the obesity epidemic might have another origin; that obesity could be an infectious disease – not just a lack of will-power. And most controversially, Dhurandhar would be implying that obesity was contagious.

Looking at maps charting the spread of the obesity epidemic in the United States over the past thirty-five years certainly gives the impression that it’s an infectious disease sweeping through the population. The epidemic begins in the south-eastern states and quickly begins to spread. As more and more people become overweight at the epicentre of the disease, it pushes outward to the north and west, affecting ever-greater swathes of the country. Hot spots crop up in major cities, setting off new bubbles of obesity that expand over time. Though a handful of scientific studies have commented on this infectious-disease-like pattern, it’s usually put down to the spread of an ‘obesogenic environment’ – more fast-food restaurants, supermarkets with calorie-dense foods, and lifestyles with ever less physical activity.

One study in people has found that obesity spreads in a manner that mimics a contagious disease even on an individual level. By analysing the weights and social connections of over 12,000 people over thirty-two years, researchers found that a person’s chances of becoming obese are closely tied to weight gain in their nearest and dearest. For example, if a person’s spouse became obese, that person’s risk of becoming obese themselves went up by 37 per cent. Fair enough, you might think – they probably have the same diet. But the same is true for adult siblings, most of whom don’t live together. More strikingly, if a person’s close friend became obese, then that person’s risk of following suit shot up by 171 per cent. It didn’t seem to be down to choosing friends of a similar weight – these people were close before the weight gain. Neighbours who were not counted as friends were exempt from the increased risk of obesity, which makes it seem less likely to be the opening of a fast-food restaurant or closure of a gym nearby that pushes the tied weight gain among social groups.

Of course, there are many possible social reasons for this phenomenon – a shared shift in attitude towards obesity, or joint consumption of unhealthy foods, for example – but a thought-provoking addition to the list of explanations is that of microbial cross-over, viral or otherwise. Even if Dhurandhar’s virus is not the main culprit, there are many other microbes to consider. Perhaps the sharing of ‘obesogenic’ members of the microbiota within social networks contributes to the obesogenic environment that other researchers perceive, and facilitates the spread of obesity. Closer friends are more likely to spend time in one another’s homes, sharing surfaces, food, bathrooms – and microbes. Sharing such microbes may allow obesity to spread that little bit more easily.

The final day of Dhurandhar’s experiment with the chickens arrived. For him, the results justified the sacrifices he and his family had made in leaving their lives and loved ones behind in India. Just as with the other virus, Ad-36 had made the infected chickens grow fat, whilst those given the alternative virus had remained lean. Dhurandhar was finally able to publish his discovery in the scientific literature, but many more questions lay ahead. Most importantly, did Ad-36 work the same way in humans? Could a virus be making people fat?