Saturday, October 11, 2014

Our Microbacterial Overlords?

A joke that I’ve heard more than once, and even made myself, is that humans are nothing more than warm sacs for our gut bacteria. There are several subtexts to this joke. The one I want to focus on is that while the human body contains at least 37,200,000,000,000 cells, or around 37 trillion cells (these guys did the most recent estimate*), the microorganisms living in and on us number ten times more (around 370 trillion cells); even so, microorganisms are small (sorry to be obvious) so they only account for about a kilo of our body mass. From the perspective of those bacteria, we are indeed a mobile unit providing them with food, shelter, and opportunities to propagate.

What is the function of all these microorganisms? I decided to look into some of the recent results of the Human Microbiome Project (HMP). The word microbiome refers to all the microorganisms that live in and on us (mostly bacteria, some fungi). Using computerized genetic sequencing techniques that we now perform quickly for large quantities of data, the HMP has given us an astonishing, if still incomplete, picture of our microbiome.

Some background. Our DNA, long protein molecules, are wrapped up into neat bundles we call chromosomes. DNA molecules contain codes for making more proteins. Proteins are like the worker bees of cells. They can be messengers, carrying chemical signals from one place to another. They can be receptors that receive those signals. They can be enzymes that help chemical reactions in the cell operate faster, or operate under energetically unfavorable conditions. They can be the molecules that are changed by the enzymes. This is far too short of a list but you get the idea.

There is extreme variation in the number of chromosomes between species and within species. In fact, the number of chromosomes isn’t much of an indicator of anything useful. What’s important is how many different proteins those DNA molecules code for. One of the surprises from the Human Genome Project was how few proteins our DNA codes for, around 20,000 proteins, about the same number as the fruit fly. (We are not special.)

The microbiome project looks for proteins that aren’t us. In fact, this is exactly the point of the microbiome itself: by acting as the host for the microorganisms, we get access to new proteins and new biochemical functions that come with them, without having to evolve the machinery, that is, the genes, to code for them. Many of these proteins are critical for our survival such as vitamins, enzymes that can utilize special nutrients, and proteins that operate within our immune system by turning it on in the first place and by causing diseases when things go awry. There are some researchers that have suggested that our microbiome may even influence our behavior; albeit fascinating, that is a topic for another day. One of the remarkable conclusions of the microbiome project, one among many, is that humans are a “supraorganism” that is a composite of both human and microbial biochemistry. So it seems that they are more our partners than our overlords (still, I think that is a debatable point). In fact, our health depends on the health of our microbiome to a fairly large extent.

There are still plenty of unresolved questions: does our microbiome vary as we age? (Probably but it still needs to be verified.) Does a healthy microbiome depend on specific species or on the general set of functions provided? Does our microbiome depend on where we live? Should we collect a lot of data from a small number of related humans located in one place or sample widely across the globe? Both designs will give interesting results but they will be answering different questions. There is plenty more to be learned from this multi-lab, multi-country research initiative.

An interesting side note: most of our microbiome is located in our gut, specifically our colons, although there are microorganisms on every single surface in and on us. So the HMP obtained some of their samples from human feces. I will never again complain about having to pick straw and cedar shavings out of chicken droppings in order to get a clean sample.

*While the current trend is towards increasing open access, which means the full publication is available online in a format such as PDF and you don’t need a subscription to get to it, many journals embargo articles for a year or two after publication. The abstract of the publication, a summary of the hypothesis and results that appears at the beginning of all scientific papers, is nearly always available without cost. There are very good reasons for embargoing papers which are beyond my scope here. Open access doesn’t necessarily mean better. It is caveat emptor in the world of open access, since any fool can create a masthead and self-publish these days, or charge other fools to publish their work, without going through that messy peer review process. In this case, the peer-reviewed article that I linked to is published in the Annals of Human Biology, which embargoes newly published articles. Nonetheless, even though you can’t read the full paper without a subscription to this journal, you can get the main points from the abstract.

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