AMERICAN GUT OVERVIEW

What is a Gut?

Overview Icons-01Your gut is an open-ended tube that runs through your body. Your gut is actually, developmentally speaking, the outside of your body, but it has evolved many intricacies that make it seem like the inside. Your gut starts with your mouth and ends with your anus. In between, food is changed into energy, feces, and a few other things. Your gut exacts a kind of metamorphosis on everything you eat, turning hotdog or grilled cheese, miraculously, into energy and, ultimately, cells, signals and even thoughts. We are only beginning to understand this process, a process in which microbes play (or fail to play) a major role.

What is American Gut?

American Gut is a project in which scientists aim to work with non-scientists both to help them (AKA, you) understand the life inside their own guts and to do science. Science is coolest when it informs our daily lives and what could possibly be more daily than what goes on in your gut? One of the big questions the American Gut scientists hope to figure out is what characterizes healthy and sick guts (or even just healthier and sicker guts) and how one might move from the latter to the former. Such is the sort of big lofty goals these scientists dream about at night (spirochetes rather than sugarplums dancing through their heads), but even the more ordinary goals are exciting. Even just beginning to know how many and which species live in our guts will be exciting, particularly since most of these species have never been studied, which is to say there are almost certainly new species inside you, though until you sample yourself (and all the steps that it takes to look at a sample happen— the robots, the swirling, the head scratching, the organizing of massive datasets), we won’t know which ones. Not many people get to go to the rainforest to search for, much less discover, a new kind of monkey, but a new kind of bacterium, well, it is within (your toilet paper’s) reach.

What is 16S rRNA?

Overview Icons-03The 16S rRNA gene is a sort of telescope through which we see species that would otherwise be invisible. Let me explain. Historically, microbiologists studied bacteria and other microscopic species by figuring out what they ate and growing them, on petri dishes, in labs, in huge piles and stacks. On the basis of this approach— which required great skill and patience— thousands, perhaps hundreds of thousands, of studies were done. But then… in the 1960s, biologists including the wonderful radical Carl Woese, began to wonder if the DNA of microbes could be used to study them and their biology. The work of Woese and others led to the study of the evolutionary biology of microbes but it also eventually led to the realization that most of the microbes around us were not culturable— we didn’t know what they ate or what conditions to grow and reproduce they needed. This situation persists. No one knows how to grow the vast majority of kinds of organisms living on your body and so the only way to even know they are there is to look at their DNA. There are many bits of DNA that one might look at, but a bit called 16S of the rRNA gene has proven particularly useful. Humans have a related gene, the 18S rRNA gene, but we use analysis techniques that do not pick up the human gene – so you don’t have to worry that your human DNA will show up on the internet by participating in American Gut.

Do you really have a robot?

Overview Icons-04Look, here is the deal. Robots. Microbiologists use robots. Personally, I think the fact that microbiologists study the dominant fraction of life on Earth, a fraction that carries out most of the important processes (and a fair bit of inexplicable magic) makes microbiologists cool. I am not a microbiologist; I am an evolutionary biologist and a writer, but I think that microbiologists are hipsters cloaked in scientists clothing (and language). But if the outrageousness of their quarry does not convince you they are hip, well, then, let me remind you, they have robots.

The robots enable the scientists to rapidly extract the DNA from thousands of samples simultaneously. Specifically, they can load your samples into small plastic plates each with 96 little wells. The robot then loads chemicals into the wells and heats the chemically-laced wells enough to break open the bacterial cells in the sample, BAM! This releases the cell’s DNA. The robots later decode the specific letters (nucleotides) of the 16S gene using the nucleotides dumped out of the broken microbial cells into these plates.

Tree of life

There is an evolutionary tree inside you. Well, sort of. When scientists study the microbes in your gut (and from the same samples we could also study viruses, bacteriophages— the viruses that attack bacteria—, fungi or even the presence of animals such as worms of various sorts) they do so by looking at the 16S rRNA gene on the swabs you send us. We compare the code of each bit of this DNA in your sample to the code from other people’s samples. As a result, we can actually use the results of your sample to map the species living in you onto an evolutionary tree. Your own genes occupy one tiny branch on the tree of life, but the species inside of you come from all over the evolutionary tree. In fact, in some people we find species from each of the major branches of the tree of life (Archaea, Bacteria, and Eukaryota) and then also many of the smaller branches. Inside you, in other words, are the consequences of many different and ancient evolutionary stories.

What is a microbiome?

A biome, as ecologists and evolutionary biologists like me historically used it is a self-contained ecosystem, where all the organisms can interact with each other and the environment in which they live, for example a rain forest is a biome for all the living things, large and small. But a single tree can be a biome for all the insects and birds just as much a single human body can be a biome for all the microbes. Therefore, a microbiome refers to a community of all the microbes and their genes interacting in a certain space, in the case of you, it’s in your gut!

What do my microbes eat?

Everyplace you have ever set your hand or any other part of your body is covered in microbes. This is true of your gut, but also everything else. Microbes live in clouds. They live in ice. They live deep in the Earth. They also live in your colon, on your skin, and so on. It is reasonable to wonder what they eat. The short answer is everything. Microbes are thousands of times more variable when it comes to their diets than are animals, plants or even fungi. Some microbes can get their nitrogen out of the air; they can, in other words, eat air. Ain’t that cool. Others, like us, eat other species, munching them in the world’s coolest and most ubiquitous game of pacman. The bacteria in your gut are also diverse in terms of their diets. If there are two hundred species of bacteria in your gut (and there probably are at least that many) then there are at least that many different combinations of things that they are eating.

Where do my microbes come from?

If you had asked this question a few years ago, we would have had to say the stork. But increasingly, we are beginning to understand more about where the specific zoo of species in you come from and it is a little grosser than the stork. If you were born vaginally, some of your gut microbes came from her vagina, some from her feces (birth, my friend, is a messy thing). Others came, if you were breast fed, from her milk. It is easiest for bacteria, it seems, to colonize our guts in the first moments of life. As we age, our stomachs become acidic. We tend to think of the acid of our stomachs as aiding in digestion; it does that but another key role of our stomachs is to prevent pathogenic species from getting into our guts. The trouble with this, well, there are a couple of problems. One is C-section birth. During C-section birth, microbes need to come from somewhere other than the mother’s vagina and feces. The most readily available microbes tend to be those in the hospital. As a result, the microbes in C-section babies tend to, at least initially, resemble those of the hospital more than they resemble those of other babies. With time, many C-section babies eventually get colonized by enough good bacteria (from pet dogs, pet cats, their parents’ dirty hands, etc.) to get good microbes, but it is a more chancy process. But then, the big question, one we just don’t know the answer to, is which and how many microbes colonize our guts as we get older. How many microbes ride through the acid bath of our stomach on our food and take up residence? We know that bad bacteria, pathogens, do this, but just how often and how good ones do it is not well worked out. You might be thinking, what about yogurt and I’ll tell you the answer, definitely, is we don’t really know. Do people who eat yogurt have guts colonized by species from that yogurt? Maybe, possibly, I bet they do, but we don’t really know (though if we get enough samples from yogurt and non yogurt eaters, we could know).

What will we discover in your gut?

Overview Icons-09When the early meetings were going on about this project, everyone sat around talking about what we might see from colon samples. One scientist was sure that we would see bacteria that looked like Elvis. Another thought we would find Shakespeare’s great lost play. But the truth is all that we are going to see from your gut are lists of strains of nucleotides. Let me explain…

Nucleotides are those hunks of which DNA and RNA are made. They come in different forms to which scientists have assigned names and letters. When the robots are done with the work, what they produce are lists of strings of nucleotides (called genetic barcodes) in all of 16S rRNA genes from all of the cells in your sample. These strings of nucleotides tell the scientists which kinds of life are in your sample (and in you). But because we will only have samples of little stretches of the 16S rRNA genes, we won’t know exactly which species are in you, just which lineages they are from. You might have the bacterial equivalent of a chimpanzee and a gorilla in you, but all we’ll know from your sample is that there was an ape. Knowing you have a bacterial ape in your gut will, on its own, not tell you so much. The real information will come from context, statistical context. I know, that sounds boring, but I promise it is not.

We think that hundreds of different things you do during your life, in addition to what your mother and father did (let’s try not to think about that), your genes and even just where you grew up influence which species of microbes are found inside you. But we don’t really know. The problem is humans are so darn complicated. What we need to be able to do is to compare large numbers of people, people who differ in many ways, to be able to sort out which variables are sometimes a little important and which ones are the big deal. Is a vegan gut very different from a vegetarian one? Does eating yogurt make a big difference? Do the effects of a C-section birth last forever? These questions require us to compare many people, which is where you come in. Your sample, gives us context and it gives you context too. It won’t be terribly exciting on its own (you will know which ancient lineages you have dividing and thriving inside you. OK, that is pretty cool on second thought), but it will be very exciting in context. Where do you fall relative to fish eaters, sick people healthy people, hunter-gatherers, or even your dog? You will know and we will know. And this is not all.

All of the questions I have mentioned so far are what I might call first order questions. How does this thing compare to that thing. But what we’d love to be able to answer are second order questions, contingent questions, questions such as whether the effect of your diet depends on your ethnicity (it probably does), whether the effect of having a dog depends on whether or not you live in the city (again, I bet it does) and so on. These questions are exactly the sort of question we have failed to be able to answer well when it comes to diet, because we don’t have big enough samples sizes. We can see the forest for all of humans. Well, that isn’t quite right, but you get the idea, we will be able to understand elaborate effects of multiple variables on the wilderness between your pie hole and the other hole and that, to us, is exciting.

A few of the stories of the evolutionary tree in your gut

Some people have least favorite bacteria. Salmonella, for example, seems to have inspired some haters. But microbiologists also have favorite bacteria, as well they should. The stories of bacteria (and those who chase and study them) are among the most important of humanities stories and include the tales of many species without which we could not live, or whose presence or absence affects how we live. These species are as fascinating and, dare I say, lovely as pandas or koala bears, just harder to see and far more significant. I have begun to compile a book of the stories of some of the most common and interesting species you are likely to encounter— whether in your own gut, on your lettuce or the next time you sink your fingers into the soil. These stories will be available online here at Invisible Life as they are compiled as a book, a book written by some of the very best science writers AND scientists out there. For starters, you might be interested to know that the smallest species on Earth is sometimes found inside humans and, once we look at your 16S rRNA genes, we will even know whether it lives in you. As more of these stories are written, they will appear here, eventually as an ebook, an ebook that you can reference when you find out what lives inside you to know whether your constant companion is a species we know everything about or, as is more typical, no one has ever studied. Like Charlie Chaplin once said… Wait, Charlie Chaplin was the one who didn’t say anything wasn’t he.

Further reading from Rob Dunn

Rob Dunn is the founder of the Wild Life of your Homes Project and the author of “The Wild Life of Our Bodies.”