Tuesday, February 5, 2013

It's the inside that counts.

Have you ever seen those people who can eat endlessly and never seem to gain a pound? 

- An inquiry by Matteo Vaiente

Glared upon them in envy and wondered why you are not gifted with the same supernatural adaptation to calorie consumption? As technology is becoming more sophisticated, scientists have begun to ask the same questions. A simple idiom is sufficient for the explanation, "It's the inside that counts," and biologists are bringing it a whole new meaning.
Microbiologists have begun exploring the symbiotic relationship between vertebrate hosts and their microbial symbionts.

That National Institutes of Health recently funded a large sequencing project, the Human Microbiome Project aimed at characterizing the microbial diversity, aka "microbiome", of 18 different body sites on 242 healthy individuals. Since then, numerous studies have examined the relationship between a healthy microbiome and those associated with various disease states. Of all your body sites, the most diverse ecosystem is maintained in the gastrointestinal tract, particularly the intestines and several scientists have correlated mircobial diversity with obesity and gastrointestinal illnesses such as IBD.

 So what does this have to do with how your friends can seemingly gorge themselves daily on McDonald's and if you so much as look at a french fry you end up looking like this? A study published in Nature  compared 22 European, 13 Japanese and 2 American microbiomes and has suggested that there are 3 "enterotypes," each with its own phylogeny and functional profile. Each of these three phenotypes is associated with a significant change in the microbial populations of at least one group of microbes in their guts. Of particular interest to our topic is what the researchers have defined as Enterotype 1, which has a much higher level of Bacteriodes than other enterotypes.

A Study published in Nature by Rey et al. in 2006 suggests that in obese people the relative proportion of Bacteriodes to Firmicutes (another important beneficial genus) is decreased. But upon sufficient weight loss, the microbiome of the previously obese subjects shifted toward a healthy proportion, suggesting that obesity likely has a microbial component, and could be manipulated to a desired physiological effect.

Naturally, scientists wanted to see if they could manipulate the microbiomes of model organisms to prove that the knowledge could be used to develop therapeutic applications and target obesity. You can think of it like a miniautrized, personalized, diet plan of the future.

Of course like many manipulative interventions, it was first tested in the mouse model. Researchers artificially manipulated the microbiomes of mice with probiotic strains in the Lactobacillus genus and were able to see an anti-obesity effect coupled with an increase in the proportion of Bacteriodes to Firmicutes. They were also able to observe a decrease in host factors related to obesity including acetyl-CoA Decarboxylase and Fatty Acid Synthase, suggesting a metabolic shift away from from energy storage pathways.

So although there is a paucity of causal evidence in human experimental models, science is currently honing in on new aspects of host metabolism and physiology that are dependent on host-microbe interactions. 
While there is still a lot more work to be done in the field, this rapidly growing field of research is providing unique insights into the structure of microbial communities in metabolic disease like type II diabetes and presents an opportunity for modern research and medicine to evaluate novel therapeutic for these diseases targeted at altering the microbiome in these diseases states. While the causative evidence is still building, the functional role of an individual bacterial species Lactobacillus reuteri  was shown to be conserved among vertebrates and also physiological adaptations of the host evolved likely to preserve bacterial association.

So why are some of us able to engorge myself without gaining a pound?
Who cares? It's the inside that counts.


1. Arora, T., Singh, S. & Sharma, R. K. Probiotics: Interaction with gut microbiome and antiobesity potential. Nutrition (2012).doi:10.1016/j.nut.2012.07.017

2. Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).

3. Ji, Y. S. et al. Modulation of the murine microbiome with a concomitant anti-obesity effect by Lactobacillus rhamnosus GG and Lactobacillus sakei NR28. Benef Microbes 3, 13–22 (2012).

4. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

5. Walter, J., Britton, R. A. & Roos, S. Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc. Natl. Acad. Sci. U.S.A. 108 Suppl 1, 4645–4652 (2011).

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