A Gut Feeling

by Meghan Rosen

Thick and thin Are you in the market for a healthy, stable, long-term relationship? Turns out you may not have to look further than your gut. Or, more specifically, the trillions of microbes that inhabit your gut. Yes, you and a few trillion life-partners are currently involved in a devoted, mutually beneficial relationship that has endured the test of time. Don’t worry though, they’ve already met your mother.

We’re exposed first to our mother’s microbial flora during birth; these are the pioneering settlers of our gastro-intestinal (GI) tract. In the following weeks our gut becomes fully colonized with a diverse array of bacteria, viruses, and fungi. Although our gut microbes are generally about an order of magnitude smaller in size than human cells, when counted by the trillions, they add up.

In fact, these intestinal interlopers (along with their fellow skin, genital and glandular neighbors) can account for up 2% of a person’s total body mass). That’s right, a 175lb man could be carrying more than 3 pounds of microbes in and on his body. Most of these microbial tenants, however, are crowded together in the lower part of his large intestine: the colon.

If we travel up the GI tract a bit and inspect the contents of the small intestine, the concentration of microbes drops nearly a billion-fold; compared to the colon, it’s practically germ free. (Although these germs are harmless when living in the gut, if the intestinal lining is breached, they won’t pass up an opportunity to spread to and wreak havoc in other areas of the body.)

While it’s easy to see the lifestyle advantages for a colon-dwelling bacterium (warm food, cozy housing, nearby relatives), the benefits and health implications for humans are not as well understood. Do we gain anything from toting around these vast microbial populations or are we merely a free meal ticket?

We know from studies in mice that gut microbes can influence health and metabolism. In fact, mice that have been delivered by cesarean section into sterile environments (and therefore lack the usual complement of intestinal microflora) are not as healthy as siblings that are birthed normally. These germ-free rodents have defective GI and immune systems compared to their microbe-ridden brothers and sisters.

While it’s clear that an animal’s gut microbes are a valuable part of a healthy intestine, their role in human metabolism and body weight remains ambiguous. We do know, however, that these microbes can enhance digestion. Normally, anything a mammal cannot digest passes through the GI tract unscathed; the energy present in this food is ‘locked up’, and therefore excreted. Obese mice, however, hold a few extra keys to calorie consumption.

The gut microbes of obese mice contain a vast array of genes that encode uncommon digestive enzymes. These enzymes help break down an expanded set of caloric compounds, and allow the mice to extract nutrients from otherwise indigestible food substances. Consequently, obese mice have fewer calories remaining in their feces than their slimmer relatives.

If obese mice have a different cohort of intestinal bacteria with super-digestive abilities, is the same true of obese humans? Is there a link between different body types and different gut microbial communities? Researchers at the Center for Genome Sciences at the Washington University School of Medicine in St. Louis, Missouri are attempting to answer these questions by comparing the identity of these gut community members, or the ‘gut microbiome’, in groups of differently sized people. Jeffrey Gordon’s lab examined fecal samples from 54 sets of adult female twins and sequenced the DNA of each and every microbe that passed through the volunteers’ intestines.

Although the majority of the twins selected for the study were identical, nearly every pair of sisters had one drastic physical difference: their body mass index. Gordon’s team of researchers specifically chose twin sets with one obese and one lean member to help understand the role of the gut microbiome in human obesity.

Although most gut microbial genes were shared between all volunteers, a significant portion of microbial genes varied from person-to-person, particularly among the obese and the lean. For instance, the obese member of a twin set generally had a gut microbiome loaded with extra genes involved in fat, carbohydrate, and protein metabolism. Are these mighty microbial metabolizers so efficient at squeezing calories from food that they actually contribute to their landlord’s obesity? Maybe, but we can’t say for sure just yet.

We do know that our gut is a kind of multi-species digestive super-organ, and that changes in the intestinal microbiome are associated with vastly different body types. In fact, Gordon’s lab has shown that you can actually fatten up a lean mouse by feeding it microbes from the guts of an obese peer. Although it’s still unclear exactly how the organisms in our intestines contribute to obesity, this research provides something for follow-up studies to chew on. Is it possible then to lose weight by dining on the gut bacteria of a skinny friend? Perhaps. Just don’t try it at home.

References:

1. Bajzer, M and Seeley, RJ (2006, December). Obesity and gut flora. Nature, 444, 1009-1010.

2. Hord, N. G. (2008). Eukaryotic-Microbiota crosstalk: Potential mechanisms for health benefits of prebiotics and probiotics. Annual Review of Nutrition, 28, 215-31.

3. Ley, R. E., Turnbaugh, P. J., Klein, S., & Gordon, J. I. (2006). Microbial ecology: Human gut microbes associated with obesity. Nature, 444(7122), 1022-3.

4. Othman, M., Agüero, R., & Lin, H. C. (2008). Alterations in intestinal microbial flora and human disease. Current Opinion in Gastroenterology, 24(1), 11-6.

5. Sekirov, I, and Finlay BB (2006, July). Human and microbe: United we stand. Nature, 12(7), 736-737.

6. Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., et al. (2009). A core gut microbiome in obese and lean twins. Nature, 457(7228), 480-4.

7. Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), 1027-31.

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