Wednesday, August 17, 2011

Nature vs Nurture in the gut microbiota, part II: the music of wallaby farts

I recently wrote about a study showing the impact of host genetics on gut microbes. This was done by comparing different strains of mice, eating about the same diet. These animals are closely related, having had common ancestors only a hundred years ago. What if we looked at animals eating about the same diet, but whose most recent common ancestor lived a hundred million years ago?

Consider the tammar wallaby: This cute little kangaroo-let has recently found interest as a laboratory animal. As a marsupial, the last ancestor it shares with a cow lived over a hundred million years ago. It eats essentially the same diet as a cow. However, while cow farts are rich in methane, wallaby farts are not. This suggests that, despite identical diets, these animals have very different gut microbes. Until very recently, the nature of these differences was quite puzzling.

It’s useful to have a little background on what goes on in the gut of a cow eating grass. Most of what the animal eats is cellulose and other polysaccharides. These are compounds that are made by stringing together hundreds of sugar molecules, and they are tough—the table that I’m writing on and the cotton I’m wearing are made of polysaccharides. Breaking these polysaccharides down to release their constituent sugars is chemically very difficult, and breaking down the cellulose found in forage is almost impossible. Surprisingly, cows can not do this. It’s a job done by microbes living in the guts of these animals. Of course, the microbes that release the sugars from cellulose don’t do it out of charity to their hosts—as soon as the sugar is freed from the cellulose, they eat it. How does this help the cow?

You probably know fermentation as what yeasts do, taking sugar and making ethanol and CO2 as wastes. However, there are other ways that microbes get energy by fermenting, and most of the microbes in a cow’s gut take sugar and make acetic acid, CO2, and hydrogen gas as wastes. So, after the microbes have broken down the cellulose and fermented the sugars, the cow thanks the microbes nicely, and absorbs the acetic acid as a nutrient. But the CO2 and hydrogen pose a real problem.

Picture a worker on an assembly line: he takes two widgets, screws them together, and passes them on to the next guy. He can keep working as long as the widgets keep coming down the assembly line and the next guy takes his finished product away. If the next guy falls asleep, the product will build up, and our worker will be unable to do his job. This is what could happen to the fermentation in a cow: CO2 and hydrogen are the products of fermentation, and if they build up, the fermenting microbes will stop (and the cow will starve). Fortunately for the cow and the microbes, there are other microbes in its gut, called methanogens, that get energy by “burning” the hydrogen—they oxidize it, using CO2 instead of oxygen, and produce methane. So, the production of methane in cow farts is absolutely necessary if the cow is to continue breaking down cellulose.

However, as was noted, wallaby farts don’t have so much methane, even though they eat the same amount of cellulose. How can wallabies and their microbes digest cellulose?

One possibility that seemed likely was that there were some other microbes in the wallaby gut that were able to eat CO2 and hydrogen. It was already known that termites (who also eat cellulose) house bacteria called “acetogens” that combine hydrogen and CO2 to make acetic acid rather than methane. So, it was thought that if an animal ate cellulose, it had to have either methanogens or acetogens in its gut to help the fermentation reactions along (and in fact, we have some of each in our guts—as evidenced by the flammability of farts—just not as many, since we don’t eat as many polysaccharides). When I first heard that wallaby farts were low in methane, I assumed that wallabies must be full of acetogens.

However, it’s always good to check your assumptions. An analysis of the wallaby gut community showed few methanogens, and somewhat more acetogens—but not enough to make fermentation (as it was understood) work. This was a real puzzle—without microbes to consume the CO2 and hydrogen from fermentation, how could the wallaby eat cellulose? The answer, according to an international group of researchers, may be that methanogens and acetogens are unnecessary for the fermentation that happens in a wallaby gut—their microbes use a unique fermentation reaction that doesn’t produce hydrogen, and consumes CO2.

The overall theme of fermentation by the cow’s microbes is to break sugars into smaller and smaller pieces—start with a molecule of six carbons, then go to two molecules of three carbons, then two molecules of two carbons and two molecules of CO2 and some hydrogen atoms.

The researchers observed that a significant component of the microbial population of a wallaby gut was similar to a previously identified bacterium called Succinovibrio, named after its unusual metabolism. Sugar fermentation in Succinovibrio starts the same way as in the cow; however, in the final stages, the fragments of sugar molecules are partially reassembled to make a four-carbon compound, succinate. This process (which also consumes CO2) provides the bacterium energy to live—and what’s more, the succinate gives the wallaby more energy than a similar amount of acetate gives to a cow.

The researchers showed very nicely that this sort of fermentation can go on in the wallaby’s gut, and that this could explain the way that wallabies are able to eat the same diet as a cow yet not produce so much methane. So, why do wallabies play host to Succinovibrio while cows play host to methanogens? It’s obviously not diet—the original studies showing differences in methane production were done with wallabies and cows on the same feed, and wallabies do host a few methanogens. There may be structural issues; cow anatomy is quite different from that of the macropodes. But most likely, as we have learned from studies on mice and humans, is that the genetic background of the host sets up a molecular environment that is particularly hospitable to specific microbes. The genomes of both the cow and the wallaby have been sequenced, so the information is there. We just have to do the hard work of understanding it.

There is a practical aspect to this question, beyond the flammability of wallaby farts. Methane is an extremely powerful greenhouse gas; it is over twenty times more efficient at retaining solar heat than CO2. The human fondness for cattle grazing has increased methane production, contributing to global climate change. There are researchers who entertain the pipedream of converting cattle to a wallaby metabolism—producing more meat per munch of hay, and producing less pollution to boot. A noble cause, but I’ll probably only be able to eat a burger from such an animal when I pull up to the drive-through in my flying car.

Paul N. Evans, Lyn A. Hinds, Lindsay I. Sly, Christopher S. McSweeney, Mark Morrison, and Andr ́e-Denis G. Wright (2010). Community Composition and Density of Methanogens in the Foregut of the Tammar Wallaby (Macropus eugenii). Applied and Environmental Microbiology 75: 2598-2602.

Emma J. Gagen, Stuart E. Denman, Jagadish Padmanabha, Someshwar Zadbuke, Rafat Al Jassim, Mark Morrison, and Christopher S. McSweeney (2010). Functional Gene Analysis Suggests Different Acetogen Populations in the Bovine Rumen and Tammar Wallaby Forestomach. Applied and Environmental Microbiology 76: 7785–7795.

P. B. Pope, S. E. Denman, M. Jones, S. G. Tringe, K. Barry, S. A. Malfatti, A. C. McHardy, J.-F. Cheng, P. Hugenholtz, C. S. McSweeney, and M. Morrison (2010). Adaptation to herbivory by the Tammar wallaby includes bacterial and glycoside hydrolase profiles different from other herbivores. Proceedings Natl Acad Sci USA 107:14793-14798.

P. B. Pope, W. Smith, S. E. Denman, S. G. Tringe, K. Barry, P. Hugenholtz, C. S. McSweeney, A. C. McHardy, M. Morrison (2011). Isolation of Succinivibrionaceae Implicated in Low Methane Emissions from Tammar Wallabies. Science 333: 646-648.

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