May 15, 2013

I can tell you the exact date that I began to think of myself in the first-person plural — as a superorganism, that is, rather than a plain old individual human being. It happened on March 7. That’s when I opened my e-mail to find a huge, processor-choking file of charts and raw data from a laboratory located at the BioFrontiers Institute at the University of Colorado, Boulder. As part of a new citizen-science initiative called the American Gut project, the lab sequenced my microbiome — that is, the genes not of “me,” exactly, but of the several hundred microbial species with whom I share this body. These bacteria, which number around 100 trillion, are living (and dying) right now on the surface of my skin, on my tongue and deep in the coils of my intestines, where the largest contingent of them will be found, a pound or two of microbes together forming a vast, largely uncharted interior wilderness that scientists are just beginning to map.

I clicked open a file called Taxa Tables, and a colorful bar chart popped up on my screen. Each bar represented a sample taken (with a swab) from my skin, mouth and feces. For purposes of comparison, these were juxtaposed with bars representing the microbiomes of about 100 “average” Americans previously sequenced.

Here were the names of the hundreds of bacterial species that call me home. In sheer numbers, these microbes and their genes dwarf us. It turns out that we are only 10 percent human: for every human cell that is intrinsic to our body, there are about 10 resident microbes — including commensals (generally harmless freeloaders) and mutualists (favor traders) and, in only a tiny number of cases, pathogens. To the extent that we are bearers of genetic information, more than 99 percent of it is microbial. And it appears increasingly likely that this “second genome,” as it is sometimes called, exerts an influence on our health as great and possibly even greater than the genes we inherit from our parents. But while your inherited genes are more or less fixed, it may be possible to reshape, even cultivate, your second genome.

Justin Sonnenburg, a microbiologist at Stanford, suggests that we would do well to begin regarding the human body as “an elaborate vessel optimized for the growth and spread of our microbial inhabitants.” This humbling new way of thinking about the self has large implications for human and microbial health, which turn out to be inextricably linked. Disorders in our internal ecosystem — a loss of diversity, say, or a proliferation of the “wrong” kind of microbes — may predispose us to obesity and a whole range of chronic diseases, as well as some infections. “Fecal transplants,” which involve installing a healthy person’s microbiota into a sick person’s gut, have been shown to effectively treat an antibiotic-resistant intestinal pathogen named C. difficile, which kills 14,000 Americans each year. (Researchers use the word “microbiota” to refer to all the microbes in a community and “microbiome” to refer to their collective genes.) We’ve known for a few years that obese mice transplanted with the intestinal community of lean mice lose weight and vice versa. (We don’t know why.) A similar experiment was performed recently on humans by researchers in the Netherlands: when the contents of a lean donor’s microbiota were transferred to the guts of male patients with metabolic syndrome, the researchers found striking improvements in the recipients’ sensitivity to insulin, an important marker for metabolic health. Somehow, the gut microbes were influencing the patients’ metabolisms.

Our resident microbes also appear to play a critical role in training and modulating our immune system, helping it to accurately distinguish between friend and foe and not go nuts on, well, nuts and all sorts of other potential allergens. Some researchers believe that the alarming increase in autoimmune diseases in the West may owe to a disruption in the ancient relationship between our bodies and their “old friends” — the microbial symbionts with whom we coevolved.

These claims sound extravagant, and in fact many microbiome researchers are careful not to make the mistake that scientists working on the human genome did a decade or so ago, when they promised they were on the trail of cures to many diseases. We’re still waiting. Yet whether any cures emerge from the exploration of the second genome, the implications of what has already been learned — for our sense of self, for our definition of health and for our attitude toward bacteria in general — are difficult to overstate. Human health should now “be thought of as a collective property of the human-associated microbiota,” as one group of researchers recently concluded in a landmark review articleon microbial ecology — that is, as a function of the community, not the individual.

Such a paradigm shift comes not a moment too soon, because as a civilization, we’ve just spent the better part of a century doing our unwitting best to wreck the human-associated microbiota with a multifronted war on bacteria and a diet notably detrimental to its well-being. Researchers now speak of an impoverished “Westernized microbiome” and ask whether the time has come to embark on a project of “restoration ecology” — not in the rain forest or on the prairie but right here at home, in the human gut.

In March I traveled to Boulder to see the Illumina HiSeq 2000 sequencing machine that had shed its powerful light on my own microbiome and to meet the scientists and computer programmers who were making sense of my data. The lab is headed by Rob Knight, a rangy, crew-cut 36-year-old biologist who first came to the United States from his native New Zealand to study invasive species, a serious problem in his home country. Knight earned his Ph.D. in ecology and evolutionary biology from Princeton when he was 24 and then drifted from the study of visible species and communities to invisible ones. Along the way he discovered he had a knack for computational biology. Knight is regarded as a brilliant analyst of sequencing data, skilled at finding patterns in the flood of information produced by the machines that “batch sequence” all the DNA in a sample and then tease out the unique genetic signatures of each microbe. This talent explains why so many of the scientists exploring the microbiome today send their samples to be sequenced and analyzed by his lab; it is also why you will find Knight’s name on most of the important papers in the field.


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