I can see it now:
“I can’t help it…it’s my stomach bacteria that’s making me fat…”
From: Greedy guts? | The Economist
Obesity and bacteria
Greedy guts?
Jan 4th 2007
From The Economist print edition
Every week seems to bring a new theory about why people are getting fatter. The latest is that intestinal microbes are partly to blame
David Simonds
ALTHOUGH most people prefer not to think about it, human guts are full of bacteria. And a good thing, too. These intestinal bugs help digestion, and also stop their disease-causing counterparts from invading. In return, their human hosts provide them with a warm place to live and a share of their meals. It is a symbiotic relationship that has worked well for millions of years.
Now it is working rather too well. A group of researchers led by Jeffrey Gordon, of the Washington University School of Medicine, in St Louis, has found that some types of microbes are a lot better than others at providing usable food to their hosts. In the past, when food was scarce, those who harboured such microbes would have been blessed. These days, paradoxically, they are cursed, for the extra food seems to contribute to obesity. Worse still, these once-benign microbes have even subtler effects, regulating the functioning of human genes and inducing the bodies of their hosts to lay down more fat than would otherwise be the case.
Dr Gordon’s research is outlined in a paper published in this week’s Proceedings of the National Academy of Sciences (PNAS) and two others published last month in Nature. In the Nature papers, he and his team reported that obese people have a different mix of gut microbes from that found in lean people?a mix that is more efficient at unlocking energy from the food they consume. Although individuals can harbour up to a thousand different types of microbes, more than 90% of these belong to one or other of two groups, called Bacteroidetes and Firmicutes. The researchers sequenced bacterial DNA from faecal samples taken from volunteers and discovered that those who were obese had a higher proportion of Firmicutes than lean people did.
Bugs in the system
This also turned out to be true in mice, and working with these rodents, the researchers discovered that the types of Firmicute found in obese animals are more efficient at converting complex polysaccharides (a form of carbohydrate that mammals have a hard time digesting by themselves) into simple, usable sugars such as glucose. In effect, the Firmicutes made more energy available from the same amount of food. The researchers were even able to make mice that had been raised in a germ-free environment fatter or thinner by colonising their guts with microbes from either obese or lean mice.
It sounds simple enough. Unfortunately, further probing showed that the story is a little more complicated, for Dr Gordon did not merely count the gut bacteria of fat and thin people?he then put some of the fat ones on a diet. As these once-obese humans lost weight over the course of a year, their mix of gut microbes changed to reflect their new, svelte status. Why this happened is not clear. It does not seem to have been a result of the composition of the diet, since the effect was the same whether people lost weight with a low-fat diet or a low-carbohydrate diet. Nevertheless, this part of the experiment suggests it is weight that determines gut biodiversity, not the other way round.
The paper published in PNAS, though, supports the idea that the bacterial mixture is cause not effect, by adding yet another element to the story. In this study, Dr Gordon took normal mice and germ-free mice, and fed both groups a ?Western? diet that was high in fat and sugar. The normal mice gained weight; the germ-free mice stayed lean.
Part of the reason was that the normal mice had microbes that made more useful sugar available. But the researchers looked more closely and found that there was even more going on. By comparing the two kinds of mice, they discovered that the gut microbes in the regular mice were tinkering with their hosts’ metabolisms, regulating them in at least two different ways.
First, they suppressed production by the mice’s bodies of a substance called fasting-induced adipose factor. This encouraged the mice to store fat. Second, they caused lower levels of another substance, called adenosine monophosphate-activated protein kinase, which made it harder for them to burn fat that they had already accumulated. The upshot is that gut microbes not only release energy from food, they also encourage bodies to store that energy as fat and to keep the fat on.
The practical upshot of this is hard to see at the moment. But if these two suppression mechanisms could, themselves, be suppressed, that might stop people putting on weight. The findings do, however, emphasise how profound the relationship is between people and their gut bacteria. These bacteria can be thought of as an additional digestive organ. Alternatively, humans might view themselves as a sort of collective organism?a human casing surrounding a vast colony of microbes. It is just a pity that this colony is working so hard on behalf of its casing that, in an era when food comes from the supermarket rather than the savannah, the result is rather too good.
