Wednesday, September 5, 2012

The human microbiome

Me, myself, us

Looking at human beings as ecosystems that contain many collaborating and competing species could change the practice of medicine


WHAT’S a man? Or, indeed, a woman? Biologically, the answer might seem obvious. A human being is an individual who has grown from a fertilised egg which contained genes from both father and mother. A growing band of biologists, however, think this definition incomplete. They see people not just as individuals, but also as ecosystems. In their view, the descendant of the fertilised egg is merely one component of the system. The others are trillions of bacteria, each equally an individual, which are found in a person’s gut, his mouth, his scalp, his skin and all of the crevices and orifices that subtend from his body’s surface. A healthy adult human harbours some 100 trillion bacteria in his gut alone. That is ten times as many bacterial cells as he has cells descended from the sperm and egg of his parents. These bugs, moreover, are diverse. Egg and sperm provide about 23,000 different genes. The microbiome, as the body’s commensal bacteria are collectively known, is reckoned to have around 3m. Admittedly, many of those millions are variations on common themes, but equally many are not, and even the number of those that are adds something to the body’s genetic mix. Related topics Obesity Body weight Nature and the environment Bacteria Diabetes And it really is a system, for evolution has aligned the interests of host and bugs. In exchange for raw materials and shelter the microbes that live in and on people feed and protect their hosts, and are thus integral to that host’s well-being. Neither wishes the other harm. In bad times, though, this alignment of interest can break down. Then, the microbiome may misbehave in ways which cause disease. That bacteria can cause disease is no revelation. But the diseases in question are. Often, they are not acute infections of the sort 20th-century medicine has been so good at dealing with (and which have coloured doctors’ views of bacteria in ways that have made medical science slow to appreciate the richness and relevance of people’s microbial ecosystems). They are, rather, the chronic illnesses that are now, at least in the rich world, the main focus of medical attention. For, from obesity and diabetes, via heart disease, asthma and multiple sclerosis, to neurological conditions such as autism, the microbiome seems to play a crucial role. A bug’s life One way to think of the microbiome is as an additional human organ, albeit a rather peculiar one. It weighs as much as many organs (about a kilogram, or a bit more than two pounds). And although it is not a distinct structure in the way that a heart or a liver is distinct, an organ does not have to have form and shape to be real. The immune system, for example, consists of cells scattered all around the body but it has the salient feature of an organ, namely that it is an organised system of cells. The microbiome, too, is organised. Biology recognises about 100 large groups of bacteria, known as phyla, that each have a different repertoire of biochemical capabilities. Human microbiomes are dominated by just four of these phyla: the Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. Clearly, living inside a human being is a specialised existence that is appropriate only to certain types of bug. Specialised; but not monotonous. Just as ecosystems such as forests, grasslands and coral reefs differ from place to place, so it is with microbiomes. Those of children in Malawi and rural Venezuela, for instance, contain more riboflavin-producing bugs than do those of North Americans. They are also better at extracting nutrition from mother’s milk because they turn out lots of an enzyme known as glycoside hydrolase. This converts carbohydrates called glycans, of which milk has many, into usable sugars. That detail is significant. Glycans are indigestible by any enzyme encoded in the 23,000 human genes. Only bacterial enzymes can do the job. Yet natural selection has stuffed milk full of them—a nice example of co-evolution at work. This early nutritional role, moreover, is magnified throughout life. Like the glycans in milk, a lot of carbohydrates would be indigestible if all the digestive system had to work with were the enzymes that it makes for itself. The far larger genome of the microbiome has correspondingly greater capabilities, and complex carbohydrates are no match for it. They are relentlessly chewed up and their remains spat out as small fatty-acid molecules, particularly formic acid, acetic acid and butyric acid, that can pass through the gut wall into the bloodstream—whence they are fed into biochemical pathways that either liberate energy from them (10-15% of the energy used by an average adult is generated this way) or lay them down as fat. The fat of the land This role in nutrition points to one way in which an off-kilter microbiome can affect its host: what feeds a body can also overfeed or underfeed it. One of the first analyses of such an effect was Jeffrey Gordon’s work on bacteria and obesity. In 2006 Dr Gordon, who works at the Washington University School of Medicine, in St Louis, Missouri, published a study that looked at the mixture of bacteria in the guts of fat and thin Americans. Fat people, he discovered, had more Firmicutes and fewer Bacteroidetes than thin ones. And if dieting made a fat person thin, his bacterial flora changed to match. Experiments on mice suggest this is not just a question of the bacteria responding to altered circumstances. They actually assist the process of slimming by suppressing production of a hormone that facilitates the storage of fat, and of an enzyme that stops fat being burned. This may help explain an otherwise weird observation from agriculture, which is that adding antibiotics to cattle feed helps fatten beasts up—though cattle treated in this way put on muscle mass as well as fat. Having shown that gut bacteria are involved in obesity, Dr Gordon wondered if the converse was true. In a study he conducted in Malawi, he revealed at a meeting last year, he found that it is. Having the wrong sort of bacteria can cause malnutrition, too. To show this, he and his team looked at 317 pairs of twins (some fraternal, some identical). In 43% of these pairs, both members were well nourished. In 7% both were malnourished. Crucially, though, in 50% of them one twin was well nourished and one malnourished.