What lives in you? It is a simple enough question. Yet, for most of history, it has been unanswerable. Finally, in just the last few years, we have begun to get a picture of the creatures on which you depend for existence, the creatures that constitute, literally, the majority of your cells, the creatures being dragged around as you cook breakfast, drive your car, shower or do anything else. It is a fuzzy picture, seen through the lenses of genes rather than through a microscope, and yet it is the best we have ever had.
What exactly do we see? One of the first things is simply which species are common and which are rare. These simple data, cloaked in technology, are a kind of breakthrough. They represent a first step into a new land, a step in which what we are able to appraise is akin to what tropical discoverers encountered in the 1800s.
Here, I am reminded of Henry Walter Bates, that explorer-scientist who embedded himself in the Amazon for several decades. While there, Bates found roughly 14,000 species of animals, of which roughly 9,000 were new to science. Bates wrote back to his colleagues in Europe about the birds, bees and especially the beetles. Every log he turned revealed to him something new and so he turned and turned, losing himself in the search to lay hold of the simplest features of the unknown, an unknown that he came to believe was everywhere, eating, mating and calling to him, leading him further down each path.
The explorers who are now revealing your body, all of our bodies, are superficially different than Bates. They wear lab coats. They do not need to go outside. They deal neither in the glamour of flittering wings nor of shimmering elytra but instead with fecal samples on toilet paper shoved into envelopes and sent to labs to be processed. One man’s feces, as they say, is another man’s rare butterfly. OK, probably no one says that, but it is true that it is just such samples through which the wildernesses of our guts are beginning to be discovered.
Recently, The American Gut project (on which, in full disclosure, I am a collaborator) revealed the results of samples of gut microbes from 1268 people. As far as I know, this is the largest human microbiome study to date, far larger than that of the Human Microbiome Project itself. In as much, it will provide a window into a variety of phenomena taking place in guts across America, including which species are common and which are rare (and hopefully, eventually, why). These scientists have come back from the jungles and announced their finds; or at least come back from the computer to announce the availability of the data. What does this look like to those of us more distant from the action, those of us waiting for a letter from the far reaches of our inner jungles? I’ll tell you. Adam Robbins-Pianka, a graduate student in Rob Knight’s lab, just sent me an email. His equivalent of Bates’ letter about the Amazon was, the more modern, “Sorry this took so long. Here they are.” I think I responded with the elegiac, “Cool.” It seems OK at this point to long for the days of Bates.
But back to the microbes. What was in there, in the email, was a list of the bacteria species found in human guts, beneficial bacteria (or at least on a species by species basis, bacteria that are best thought of as beneficial until proven otherwise). There were a total of just over 1000 species, fewer species than I would have expected and yet more species, for example, than there are species of mammals in the Americas. For these species, Adam tallied for me two types of commonness, how many of the 1268 people they were found in and, when in those people, a crude measure of their relative abundance (for those in the know, the proportion of reads which they constitute). As I’ve said elsewhere, in considering another habitat, belly buttons, these kinds of commonness relate to those we think of in rain forests or other macro ecosystems. In macro-ecosystems, the purview of our ordinary daily experience, species that are both frequent, and when present, abundant play a disproportionate role in ecosystem process—if they are trees, they make the most leaves, if they are termites they decompose the most matter, if they are ants they eat the most termites. It is reasonable to believe the same is likely to be true of bacteria. If they are the most common bacteria on our skin or in our guts, well, they are the most likely to benefit or cost us, to do something of consequence one way or another. We can’t rule out that rare species also matter. Some definitely do. An initially rare pathogen, for example, can prove deadly. But we know that the common species matter and if they are both common and frequent, they matter on nearly all of us; they should be the ones we all know. But they are not.
Figure 1. The first thing one sees in looking at these data is that those species found on many people (to the right on the panel above) tend to be the same ones that are abundant when present (higher values on the y-axis), which is to say, with a few interesting exceptions, there are true oligarchs in the gut, species that dominate human guts, species that are undoubtedly among the most common on Earth, species that number in the trillions in every room you have ever gone into, because you bring them with you.
As revealed by the American Gut data, the very most common bacterium in the human gut is a rod-shaped species of the genus Bacteroides (in the family Bacteroidaceae). It appears in nearly all adults. It is also one of the best-studied species in the gut and yet, by any realistic reckoning, it is more poorly known than the rarest bird species of the Galapagos. What we do know, is that when present, this species is abundant, the white oak of the intestines. And when abundant, this microscopic oak benefits you everyday. Conversely, where it is rare, problems seem to arise, obesity, inflammation, diarrhea. You can take the girl out of the city, in other words, but you shouldn’t take the Bacteroides out of the girl.
(Rarer species of Bacteroides, of which there are many, possess their own superpowers, such as the ability to digest sushi seaweed, an ability discovered in a Bacteroides species found, so far, only in Japanese guts. What specialties lurk in the other strains found here one can only speculate).
Whereas Bacteroides is common in essentially everyone, one of its cousins, a species of Prevotella, the seventh most common species in the American Gut samples, becomes more common in vegetarians. Meanwhile, a species of the related Parabacteroides is also very common, but all we know about it is what we can infer about its biology based on its relatives. “If Parabacteroides is like Bacteroides,” the sentence begins, it is likely to be similar. But then again, just as when someone makes the same assertion about you and your kin, such assertions are not always true.
The second most common bacterial species in the gut, a species found in all but one hundred of the twelve hundred people who sampled themselves, does not yet have a name. Neither does the genus to which it belongs. All we know is that it is very common and is a member of the family Ruminococcaeae. Yes, the second most common species in human guts does not even correspond to a named genus. Yes, this species is probably helping to sustain your life and lifestyle, even though it has no name. Yes, naming and better understanding this species seems very important, but no one has gotten to it yet. I suspect no one will for a while. Such are the realities in a new land. The mapmakers are few relative to the dimensions of the terra incognita, the miles of hills and valleys of our inner continents.
Another unnamed species of the genus Faecalibacterium in the same family is the third most common species. Both this and the Ruminococcaceae species are members of the bacterial order Clostridiales which also includes the fourth most common species of bacteria in guts, a species of the family Lachnospiraceae, and the fifth most common species, a Streptococcus. Streptococcus species are most often found in the mouth and stomach where they can be mild pathogens; just what they are doing in the gut (= large+ small intestines) is less clear. As for species of Lachnospiraceae,they are fiber specialists. They need the stringy, hard to digest stuff to thrive. In the absence of fiber, they grow rare. When they go rare, our risk of certain cancers may go up.
The Clostridiales also contain the thirteenth (Ruminococcus), sixteenth (Veilonella), eighteenth (Coprococcus), and nineteenth (Clostridium) most common species. The very worst species of Clostridium, “C. diff.,” can be deadly, but most are not. Just what turns a good Clostridium bad, we don’t know. Could we use good Clostridium to fight bad?
The fourteenth most common bacteria in fecal samples, a species of the genus Akkermansia (in the family Verrucomicorbiaceae) may actually be more common than it seems from these samples. It is so intimately associated with the gut lining that it may “wash out” in fecal samples less often than other species. Species of Akkermansia seem to be tightly linked to obesity and inflammatory disorders. Treat them poorly, at the expense of both, it seems, your slender figure and your health.
Also on the list of the top twenty bacteria in your gut are three species that while present in many studies, usually don’t get mentioned. They are listed in the tables of who was present without comment. Could they be incredibly important? Maybe. Probably. Maybe not. At number 9, Neisseria is very abundant when it is present. Interestingly, it is absent in about half of those people sampled. What does that mean? We don’t know. Also, a species in the family Planococcaceae (that could not readily be assigned to a genus) is the tenth most common and a species of the genus Rothia is twelve most common. That is all I can tell you. Frankly, how little we know about these common species is scandalous and, as a biologist, thrilling.
The twentieth most common microbial species in human guts is actually the result of a bit of evolutionary chicanery. As is now well-documented and was originally advocated by Lynn Margulis, the chloroplasts in plants, those power centers in which sunlight is converted into sugars, are actually the descendants of cyanobacteria that were ingested by the species from which the rest of the plant cells descend. It is, in other words, a bacterium inside a plant. As a result of this history, when someone has plant material in their gut we see the evidence in the form of chloroplast-bacterial DNA.
Of course, among a thousand species, there are also many others that are sometimes common or interesting in other ways. With the help of some talented science writers, we’re trying to share many of these species’ stories with you via essays contributed to our Invisible Life Project. For example, a species of Bifidobacterium commonly found in breast milk was found in 881 people (though it was rarely abundant even though often present). Florence Williams writes about this species and breast milk more generally. It turns out breast milk is a smorgasbord of microbial goodness, a goodness lost on a generation of formula-feeders.
A species of Corynebacterium was very frequent, but this is likely an artifact of sampling in as much as Corynebacterium, as Veronique Greenwood describes, is usually a skin bacterium, one which might have been rubbed onto toilet paper samples by overly eager participants. Staphylococcus skin bacteria were also common, presumably for the same reason.
A species of Lactobacillus was found in 661 participants. This species is probably one of the same ones found in yogurt, as Christina Agapakis expounds. Perhaps it is more common in those who consume yogurt with active cultures. A large industry is predicated on this idea; it would be nice to test this assumption.
Two hundred and seven people housed methanogens, microbes that produce methane. Those individuals, as Gilberto Flores points out, may actually be contributing to global warming one fart at a time.
Five hundred and sixty six people supported populations of a species of Pseudomonas. Pseudomonas species can, as Gaddy Bergmann points out, go bad, though they usually don’t.
And all of this is just a glimmer of what is really going on, a measure of what we see leaving the gut. We are, in a way, earlier in the story of the discovery of what is going on in our guts than Bates was in the Amazon. At least he could chase the birds and insects that fascinated him. Our ability to chase is limited. We use tools through which we see the microbes indirectly. We fumble with colons filled with species on which we clearly depend shining the diffuse but weak light of our modern techniques. Upon noting what it has revealed, we send emails to each other saying, “Look what I have found, pretty cool.” And then we get back to looking, scribbling away with the ones and zeros of our modern notebooks with an eagerness Bates would have recognized, an eagerness to lay hold of what is ever more obviously mostly unknown.