Microbes 'R' us

Olivia Judson - A New York Times Blog
A New York Times Blog
July 21, 2009, 9:30 pm
Microbes ‘R’ Us
hand microbes Agence France-Presse/Getty Images
There are 150 species right at your fingertips.

This week, the 40th anniversary of the first moon landing, there’s much talk of exploring other worlds. Which is exciting and grand; such is the stuff that dreams are made on. Yet we don’t need to go abroad to find amazing new life forms. We just need to look at the palms of our hands, the tips of our fingers, the contents of our guts.

The typical human is home to a vast array of microbes. If you were to count them, you’d find that microbial cells outnumber your own by a factor of 10. On a cell-by-cell basis, then, you are only 10 percent human. For the rest, you are microbial. (Why don’t you see this when you look in the mirror? Because most of the microbes are bacteria, and bacterial cells are generally much smaller than animal cells. They may make up 90 percent of the cells, but they’re not 90 percent of your bulk.)

This much has been known for a long time. Yet it’s only now, with the revolution in biotechnology, that we’re able to do detailed studies of which microbes are there, which genes they have, and what they’re doing. We’re just at the start, and there are far more questions than answers. But already, the results are astonishing, and the implications profound.

Even on your skin, the diversity of bacteria is prodigious. If you were to have your hands sampled, you’d probably find that each fingertip has a distinct set of residents; your palms probably also differ markedly from each other, each home to more than 150 species, but with fewer than 20 percent of the species the same. And if you’re a woman, odds are you’ll have more species than the man next to you. Why should this be? So far, no one knows.

But it’s the bacteria in the digestive tract, especially the gut, that intrigue me most. Many of these appear to be true symbionts: they have evolved to live in guts and (as far as we know) are not found elsewhere. In providing their habitat — a constant temperature, some protection from hostile lifeforms and regular influxes of food — we are as essential to them as they are to us.

And they definitely are essential to us. Gut bacteria play crucial roles in digesting food and modulating the immune system. They make small molecules that we need in order for our enzymes to work properly. They interact with us, altering which of our genes get turned on and off in cells in the intestinal walls. Some evidence suggests that they are essential for the building of a normal heart. Finally, it seems likely that gut bacteria will turn out to affect appetite, as well as other aspects of our behavior, though no one has shown this yet. (Imagine the plea: I’m sorry, sir, my microbes made me do it.)

Together, your gut microbes provide you with a pool of genes far larger than that found in the human genome. Indeed, the gut “microbiome,” as it is known, is thought to contain at least 100 times more genes than the human genome. Moreover, whereas humans are extremely similar to one another at the level of the genome, the microbiome appears to differ markedly from one person to the next.

What determines these differences? Good question. Diet has some effect: a diet rich in sugars and fats reduces the diversity of gut bacteria, and shifts the balance towards those that are more efficient at extracting energy. Start eating more plants and you can shift the balance back, and increase the diversity of your gut microbes. Your own genetic background may play a role as well, though we are far from understanding how, or how much. It probably also matters which other microbes are present: as in any ecosystem, relationships among different inhabitants are likely to be complex.

(At this point, I’d like to introduce a caveat. We know that the diversity of microbial species differs between your gut and mine, and that the less related we are, the more that will be true. Family members tend to have more similar gut microbes than nonrelatives, and preliminary evidence suggests that geography matters, too. So the gut microbes of people in China are different from those of people in the United States — though whether this is due to diet, human genes or geography is entirely unknown. But despite this variation at the species level, we don’t yet know how much variation there is at the genetic level. It may be that different sets of gut microbes provide broadly equivalent sets of genes.)

Naturally, a huge effort is now underway to see whether differences in gut bacteria are responsible for differences in health. But what interests me most about all this is that it suggests another mode of human evolution. Bacteria evolve quickly: they can go through many thousands of generations for every human one.

This has two potential consequences. First, during your lifetime, your bacteria can change their genes even though you cannot change yours. (You do have some flexibility: your immune system has a built-in capacity to change.) It may be that gut bacteria evolve in response to short-term changes in the environment, especially exposure to food-borne diseases. They may thus act as an evolving supplement to the immune system.

The second potential consequence is further reaching. Because bacteria can evolve so fast, it may be that some of what we think of as human evolution — like the ability to digest new diets that accompanied the invention of agriculture — is actually bacterial evolution. We know that hostile bacteria — those that cause diseases in ourselves and our domestic plants and animals — have undergone dramatic genetic changes in the last 10,000 years. Perhaps our friendly bacteria have, too.

Notes:

For human cells being outnumbered by microbial cells by a factor of 10, see Savage, D. C. 1977. “Microbial ecology of the gastrointestinal tract.” Annual Review of Microbiology 31: 107-133. For new techniques in analyzing microbes that we cannot grow in the laboratory see, for example, Marcy, Y. et al. 2007. “Dissecting biological ‘dark matter’ with single-cell genetic analysis of rare and uncultivated TM7 microbes from the human mouth.” Proceedings of the National Academy of Sciences USA 104: 11889-11894.

For bacteria living on hands, see Fierer, N. et al. 2008. “The influence of sex, handedness, and washing on the diversity of hand surface bacteria.” Proceedings of the National Academy of Sciences USA 105: 17994-17999. For gut microbes not being found elsewhere, see Ley, R. E. et al. 2008. “Worlds within worlds: evolution of the vertebrate gut microbiota.” Nature Reviews Microbiology 6: 776-788.

For a summary of the essential roles that gut microbes play, see Turnbaugh, P. J. et al. 2007. “The human microbiome project.” Nature 449: 804-810. For estimates of the number of genes contained in the microbiome, see Gill, S. R. et al. 2006. “Metagenomic analysis of the human distal gut microbiome.” Science 312: 1355-1359.

For diet affecting human microbial diversity, see Ley, R. E. et al. 2006. “Human gut microbes associated with obesity.” Nature 444: 1022-1023. For “obese” microbes harvesting more energy, see Turnbaugh, P. J. et al. 2006. “An obesity-associated gut microbiome with increased capacity for energy harvest.” Nature 444: 1027-1031. For initial evidence that the genetic background of the host affects which microbes are present, see Rawls, J. F. et al. 2006. “Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection.” Cell 127: 423-433.

For differences in gut microbes between people in China and the United States, see Li, M. et al. 2008. “Symbiotic gut microbes modulate human metabolic phenotypes.” Proceedings of the National Academy of Sciences USA 105: 2117-2123. For evidence that different sets of gut microbes can provide broadly equivalent sets of genes, see Turnbaugh, P. J. et al. 2009. “A core gut microbiome in obese and lean twins.” Nature 457: 480-484.

For recent and dramatic genetic changes to our hostile bacteria, see Mira, A., Rushker, R. and Rodriguez-Valera F. 2006. “The Neolithic revolution of bacterial genomes.” Trends in Microbiology 14: 200-206.

Many thanks to Rob Knight and Jonathan Swire for insights, comments and suggestions.