Thursday, January 11, 2007

How the microorganisms in your gut can make you fat...

Blogging around here has been slow lately - now that the crazy holiday season is over, I'm immersed in an essay I'm writing on the remarkable use of science in Thomas Pynchon's latest novel Against the Day. I think what Pynchon did in this novel has been severely underappreciated in the reviews that have been published, because you have to have enough awareness of the science to pick up on Pynchon's references and see what he's doing with them. One example: at one point in the novel a character (who is a math student studying Riemann manifolds) walks through a brick wall; Pynchon is playing around here with the notion of 'cuts' on a Riemann surface.

There's a whole lot more, and I'm putting something together that will hopefully be fun for Pynchon fans with little science background, induce scientists who haven't read a Pynchon novel to pick one up, and not make people who are both Pynchon fans and scientists cringe.

In the mean time, I have to highlight some recent papers that have come out of Jeff Gordon's lab here at the Center for Genome Sciences. The Gordon lab studies the interaction between the genes of mice and the microorganisms that live in their guts. We all have many, many different types of microorganisms living inside our intestinal tract, and the Gordon lab has been studying how that population of microorganisms impacts how we process food for energy. This is how the Gordon lab puts it in their most recent paper:

"The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus."

This paper reports that mice without these gut microorganisms don't become obese when fed a high-fat, high-sugar diet, and identifies several enzymes that may be related to this resistance to obesity.

The December 21/28 issue of Nature featured the Gordon lab's research on the cover and contained this paper and this paper connecting obesity with gut microbiota.

The studies look at the types of microorganisms present in the guts of obese mice and humans, compared with lean mice and humans. The group also has studied how these microorganisms "harvest energy from the diet."

These studies rely on mice with defined populations of gut microorganisms and genome sequencing. To look at what's living in a particular mouse's gut, you isolate some fecal samples from mice with various mutant genes, and then sequence the DNA to find out what's in there. The Gordon lab has germ-free mice - mice born without any microorganisms in their guts and kept sterile until the researchers add a defined population microorganisms. So you can take the microbiota from an obese mouse, put it in the gut of a germ-free lean mouse, and see if that lean mouse becomes obese.

Of course I'm really simplifying a lot here; I suggest checking out the abstracts I've linked to. This is an interesting, innovative way to use sequencing to study genes and health.


Dave said...

I found those studies very interesting as well, but i wonder if the changes in flora are a cause of obesity or a response to increased lipid diets.

Mike said...

That is a very good, important point (one that my very casual title to this post ignores). It's an issue that has come up repeatedly in local Center for Genome Science talks by the authors.

They do try to address this point - for example, in the Nature article (Turnbaugh et al), when germ-free mice are colonized with 'obese microbiota' (bugs from obese mice), these mice show an increase in body fat after two weeks, compared with germ-free mice colonized with 'lean microbiota.'

Robrschafr said...

yqqgoZI know nothing of microorganisms . But I do love Pynchon's writing. I get some of the science in "Against the Day", but clearly not enough. Put me down as one who is waiting for some Light to be shed..........and thanks in advance......Robert

Mike said...

I'm glad you're interested in the science in Against the Day - Pynchon does some really interesting stuff with the science he references.

I hope to have some sort of a draft out soon, which I'll post here.