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

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СКАЧАТЬ 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 СКАЧАТЬ