Microbes ‘R’ Us (Very Good Article)

[Guest guest]

Microbes `R' Us

July 21, 2009

 

 

 

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 under way 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.,

Pushker, 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.

 

http://judson.blogs.nytimes.com/2009/07/21/microbes-r-us/?pagemode=print