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