Every Man an Island, Pt. 2(Continued from part 1)
Why we are islandsIn the previous post we have seen how our bacterial population affects our weight and that by changing our dietary habits we can change the species composition in our guts. Also, we saw how a metagenomic analysis can lead to verifiable hypotheses: using a metagenomic analysis, Gordon's lab discovered that the microbiome in the guts of obese mice have a high level of bacteria from the Firmicutes division; they also found that they contain a high level of carbohydrate-active enzymes or CAzymes. These CAzymes break down sugars in our foods more efficiently, extracting more calories that contributes to weight gain in a vicious cycle. At the same time, other studies have shown that there is a large diversity of species in the human gut, at a finer resolution than the broad divisions of Firmicutes and Bacteroidetes. But how really diverse are our gut bacteria? And how is this diversity affected by our own genetic makeup, what we eat, and how fat we are? Some answers were published in last week's Nature. Gordon's group compared the microbial content of the feces of adult twins, both fraternal and identical. The goal was to try and assess the contribution of the genetic makeup and contrast it with the environmental contribution. Since the twins were adults, most of them (70%) were not living together, thus exposed to somewhat different environments. In addition, stool samples were taken from the twins' mothers (where available), and controls were taken from pairs of unrelated individuals. Also, each participant in the study contributed stool samples in different time periods, for self-comparisons. All this data was analyzed to receive a better picture of how different factors affect our gut microbiome. The factors that were analyzed were genetic makeup (genotype), environment and, of course, body weight. The differences that were analyzed were the bacterial species inhabiting twins (identical and fraternal) twins and mothers and pairs of unrelated people; all individuals were also tagged as obese and lean. The other set of differences that were analyzed were functional differences: how different were the frequencies of CAzy genes between the pairs of twins and non-twins, obese and non-obese in this study. What they found was that identical twins were no more alike than fraternal twins, or unrelated individuals when the differences between bacterial species that constitute their respective microbiomes were analyzed. In other words, you cannot really say if two different samples, or even population of samples come from siblings (identical twins or otherwise), related family members, or just unrelated individuals. Furthermore, there was not a single common bacterial species that was found to be common in an abundant frequency in the guts of all 154 people in this study. This is where the title of this two-part post finally becomes clear: every man is an island, populated by a unique set of bacteria. We are quite different in the population of species of bacteria that inhabit our guts. Furthermore, our gut bacteria species are quite different today than they were two months ago, according to this study. So not only our we islands, but we have a serious population turnover as well. Still, our gut microbiome can be regarded as a "tissue" same as our liver, or lungs. Our bacteria take up certain foods in our digestive tract and break it down to make it available to us. Different bacterial species maybe, but they end up doing almost the same things, as was revealed in the second part of this study. This part of the study shows that, in contrast with species distribution, there is an identifiable core set of bacterial metabolic pathways in our guts. Furthermore, certain core pathways were identified between obese individuals, but not between obese and lean individuals. One memorable scene in Monty Python's Life of Brian is when Brian, the unwilling faux messiah tells the crowd of worshipers he is trying to rid himself of : "You are all individuals". To which the huge crowd replies, in unison: "Yes! We are all individuals!" He continues saying "You are all different!" and they answer in one voice "Yes! We are all different!" (The first minute of this clip is relevant). Somehow, this is similar to what is going on in our individual microbiomes. We are all different: we have quite different bacteria. But in terms of what they do, they do pretty much the same things. The functional differences between individuals are much less than the species differences. OK, yes, we are comparing different metrics: differences between the lump sum of functions are measured differently than differences between the lump sum of species. I won't get into that here, there is a link to the paper at the end of this post for those wishing to delve into the methods used. All that being said, obese individuals had less species diversity than lean individuals, but whether two obese individuals were related or not was almost irrelevant. The cause and effect fro this observation were not dealt with here: are people fat because of their more uniform and better sugar harvesting microbiome, or does their diet cause that? In a previous study of humans, it was shown that dieting humans do change their bacterial flora, so free will may have hope. Like any good scientific study, this one answers a few questions, but raises more: how do bacterial populations assemble themselves in our gut to perform the same functions in all human beings? Could an ecological misassembly be at least partially responsible for obesity? We are still not sure how much of our own genomic makeup contributes to this, although it may seem that the contribution is not large. I would like to finally do some justice to John Donne, whom I have quoted partially and out of context. When saying "No man is an island", Mr. Donne was not talking about our microbial world; he was talking about our spiritual one, and about one of the most fundamental aspects of it, our perception of human mortality. Here is the paragraph from Meditation XVII. I linked the title to the full text of Meditation.
No man is an island, entire of itself; every man is a piece of the continent, a part of the main. If a clod be washed away by the sea, Europe is the less, as well as if a promontory were, as well as if a manor of thy friend's or of thine own were: any man's death diminishes me, because I am involved in mankind, and therefore never send to know for whom the bell tolls; it tolls for thee.
Further reading: Peter J. Turnbaugh, Micah Hamady, Tanya Yatsunenko, Brandi L. Cantarel, Alexis Duncan, Ruth E. Ley, Mitchell L. Sogin, William J. Jones, Bruce A. Roe, Jason P. Affourtit, Michael Egholm, Bernard Henrissat, Andrew C. Heath, Rob Knight, Jeffrey I. Gordon (2008). A core gut microbiome in obese and lean twins Nature, 457 (7228), 480-484 DOI: 10.1038/nature07540
If this discussion piqued your interest, and you would like to learn more about humans, microbes and their relationships, I recommend this book. Clarification: I have nothing to do with the author, the publisher, or Amazon.com to which I link from simple convenience. I read this book, and I liked it, that's all.