I've got to do something about this root beer belly!

Guys, I'm sure you've noticed those extra pounds have slowly tacked on as you've gotten married, gotten a desk job, gone to college, or just gotten old. Well, thanks to some smart scientists, and a next generation sequencing method from 454 Life Sciences, we now understand a little more about obesity and how to control it. Scientists at Washington University in St. Louis, Missouri have identified several types of bacteria in the human gut that favor obesity.

Before diving in further, a little bit of background is necessary. First, let's do a brief review of Biology 100. DNA is in every cell of your body and is essentially a blue-print of your body. This means that every cell has the information for every gene in your body, but only certain genes are "turned on" in certain cells. The "turning on" of genes is usually manifested as RNA, a copy of a specific segment of DNA that then codes for a specific protein that the cell is supposed to produce.

Next, sequencing is the process of identifying the order of nucleotides in a segment of RNA or DNA. Simply put, sequencing is a way to figure out exactly what the blue-print says.
A 454 sequencer is a machine that will sequence up to 500 million bases in segments of 400-500 bases (the letters that make up DNA or RNA). To give you an idea of how amazing a feat this, when the human genome project began we could only sequence 20,000 bases at a time and two years ago we could only sequence 100 million bases. Also, to give you a benchmark you can compare this with, the human genome consists of approximately 6 billion bases.

Finally, in addition to the genes that are expressed in the human gut, bacteria also express their own genes that in turn greatly affect our metabolic processes. The expression of genes from bacteria in a host is referred to as a biome. The paper I'll discuss is studying the human gut microbiome or the expression of genes from bacteria and how they interact with our bodies. Now onto the papers!

Researchers in Missouri began by taking fecal samples from obese and lean mice and sequencing the DNA found in the sample. After a classification process, they found that 94% of the DNA in the samples was bacterial DNA (that should make you feel warm and fuzzy). When comparing the obese sample to the lean sample they found that Bacteroidetes and the Firmicutes, two families of bacteria, varied between the samples. In the obese mouse they saw an increased ratio of Firmicutes to Bacteriodetes compared to the lean mouse. They then looked at the sequences in Firmicutes and saw that its products are involved in KEGG pathways which control the digestion of many carbohydrates. This meant that the obese mice were obese because Firmicutes bacteria was breaking food down better and allowing the mouse to get more calories from its food than the lean mouse.

To verify their findings, the researchers then analyzed the mouse feces and found that it had less energy remaining in the obese mouse than the lean mouse. They further tested this by transplanting the microbiome of obese and lean mice into germ free mice. The mice with the obese microbiome transplanted into them became showed greatly increased weight after only two weeks than the mice with the lean transplanted microbiome. The mice ate the same amount of food and water and started with the same wieghts and body fat. The only thing that changed was the transplanted microbiome.

Researchers in Shanghai have continued this work by looking at the same bacterial differences in humans. They have looked at Chinese and American lean and obese individuals and have found the same phenomenon happening in humans. They did find that a diet low in carbohydrates and fats decreases the amount of Firmicutes in the gut microbiome. This in turn would decrease an individuals ability to get more energy out of food, a beneficial attribute if you would like to lose weight.

In conclusion, there is hope for those with a root beer belly you'd like to lose. Further research into this field will probably yield drugs that will help regulate the amount of Firmicutes in the gut which will reduce energy uptake and decrease obesity. But until then, if you don't eat as many carbs or fats you'll decrease the amount of Firmicutes naturally which should also decrease obesity. Personally, I'm holding out for the drug!

Here are the references for the two papers I used for this article if you're interested:
Ley, R.E., et al, (2006). "Microbial ecology: Human gut microbes associated with obesity." Nature 444: 1022-1023.
Li, M., et al. (2008). "Symbiotic gut microbes modulate human metabolic phenotypes." PNAS 105 (6): 2117-2122.