American Gut

American Gut

Most of us have heard at some point or another that we have entire ecosystems of microbes living in our gut. Mostly of these microbes are happy symbionts that help us digest our food, but some can occasionally becoming pathogenic and cause health problems. Have you ever wondered what your gut microbial community looks like? Now you can find out! The Earth Microbiome Project (http://www.earthmicrobiome.org/), founded several years ago with the ambitious goal of “sequencing the microbiome of planet earth”, (or, in other words, characterizing basically all of the genetic diversity that exists on our planet), has begun a smaller, more targeted project with the aim of characterizing the gut communities of human populations.

Some of the key science questions driving this project : to what extent do gut microbial communities vary among people? At what scales can we discern patterns in microbial community composition? Are similar microbial communities found among people from similar geographic regions, with shared genetic history, or with a shared diet? And, perhaps more interestingly to most of us, to what extent does the composition of our gut community impact our own health? Once we have enough data to start answering some of these basic questions, perhaps we can even start making predictions about what sorts of lifestyles will lead to what sorts of gut flora, and how these communities, in turn, will impact our overall health.

It costs just $100 to join and get your microbiome sequenced. And the information could change your life!

Back to the future- ecosystem memory in environmental metagenomes

Over the past two decades, the study of ecology has been revolutionized by the advent of molecular genetics techniques. Originally developed with only biomedical applications in mind, some forward thinking ecologists quickly realized the possibilities that these technologies could offer. One of the fastsest growing areas of environmental research is metagenomics, the study of pooled genetic material from an environmental sample. In a gram of soil or a droplet of seawater, millions of unique species of bacteria exist with their own unique genetic make-up. Combine an enormous number of bacteria with even more abundant viruses- naked fragments of DNA encased in a protein coat that serve no other purpose than to infect living cells and hijack their DNA replication machinery- and you have a metagenome.

Thanks to a handful of pioneering scientists, scientists can now take a sample from practically any environment- soil, ocean water, subsurface rocks, or cloud water, to name a few, and sequence its “genome”. The genes obtained from an environmental sample indicate the total potential that the sample is biologically capable of.

What sorts of information is metagenomics providing us? Genes present in environmental samples encode proteins that perform numerous ecosystem functions- enzymes that decompose organic matter and release carbon, nitrogen and phosphorus, as well as numerous important micronutrients. Proteins that detoxify organic wastes, or convert inorganic gases such as carbon dioxide into sugar.

A major challenge moving forward from genomic information to understanding, at the most fundamental level, how an environmental system functions, relates to the fact that a genome is not a reflection of every process going on in a system, but rather an indication of what that system is capable of. Only a fraction of your body’s genes are being translated into proteins at any given time- some are turned on or off at certain points in your life, and some are only activated under the proper environmental conditions.

The mechanisms underlying gene expression in humans are still  largely unknown, but it is becoming increasingly clear that in microbial metagenomics, gene expression is highly sensitive  to external stimuli. The emerging framework for microbial gene expression is actually strikingly similar to economic resource allocation theory. Why waste time and energy producing a protein to degrade cellulose if there is no cellulose in your vicinity? Why produce nitrogenase, the protein responsible for taking inert atmospheric nitrogen and converting it into a form useable by plants, if there is already abundant organic nitrogen in the soil? Proteins represent an energetic cost, and microbes exist in a competitive, resource limited environment where any misallocation of resources almost certainly compromises your chances of survival.

Given that microbes will only express those genes that provide the maximum return on investment, what does a metagenome really tell us? Memory. As ecologists begin to push forward from examining metagenomes to studying gene expression and protein expression in environmental samples, Mary Firestone, one of the pioneers of the field of molecular microbial ecology, encourages her colleagues to look “back to the future”. All the genes present in a sample, she argues, provide a written history of what the environment has been like in the past. Resource allocation theory and evolutionary theory tell us this. Why would a gene be present, if there wasn’t a selective advantage to it at some point? Much as paleontologists can study changes in dinosaur morphology over time and infer changing environmental conditions, microbial ecologists can use metagenomics to infer what must have been the conditions at some point in the past. And if something occurred in the past to select for a bacteria carrying a particular gene, it may well happen in the future. Carbonic anhydrase is a protein commonly found in surface seawaters that is responsible for converting dissolved CO2 into bicarbonate, and in doing so acidifies the environment. The presence of carbonic anhydrase encoding genes in a seawater sample may indicate a past in which CO2 concentrations were much higher. Forward thinking about how to deal with new genomic information may in fact be a history lesson.