In the past few decades, researchers have opened up the extraordinary world of microbes living on and within the human body, linking their influence to everything from rheumatoid arthritis to healthy brain function. Yet we know comparatively little about the rich broth of microbes and chemicals in the air around us, even though we inhale them with every breath.
This struck Stanford University genomics researcher Michael Snyder as a major knowledge gap, as he pursued long-term research that involved using biological markers to understand and predict the development of disease in human test subjects. “The one thing that was missing was their exposure” to microbes and chemicals in the air, Snyder says. “Human health is clearly dependent not just on the genome or the microbiome, but on the environment. And sampling the environment was the big hole.”
In a new study published September 20 in Cell, Snyder and his co-authors describe their efforts to fix that. They aim to do so with a wearable device that monitors an individual’s daily exposure to airborne bacteria, viruses, protozoa, fungi and chemicals—the so-called exposome. Similar studies in the past have largely relied on a few fixed sampling stations; the Stanford researchers instead modified an existing monitoring device, the size of a big kitchen matchbox, to be strapped to a person’s upper arm or kept nearby. The device continually sipped the air around the 15 test subjects at home, at work and on the road, passing the air through separate filters to collect both biological and chemical compounds. DNA sequencing, together with comparisons of the results against a reference genome database of 40,000 species, indicated that the 15 participants had been exposed to 2,560 biological species—more than a thousand of those after wearing the device for just three months.
Mass spectrometry analysis added 3,300 chemical signals to the mix. The researchers were able to identify fewer than a third of them—but they note that all the chemicals had passed through a pore-sized filter for the biological assay and could thus potentially reach deep into a person’s lower respiratory tract. Almost all of these samples contained diethylene glycol, used in products from brake fluid to skin cream. The insect repellant DEET also popped up everywhere, apparently an artifact of sampling mainly during the San Francisco area’s insect-friendly springtime. The study calls this “a previously unrecognized type of potentially hazardous exposure,” noting that no government agency “has evaluated possible health risks associated with inhalation” of such compounds.
Snyder and his co-authors suggest that any given person’s exposome is a product of two separate but interacting “clouds”—a term redolent of the dusty shadow around the character Pig-Pen in the Peanuts cartoon. One cloud is environmental and shared with immediate neighbors; the other is more personal, consisting of human- and pet-centric bacteria, fungi, parasites and protozoa. The test subjects lived scattered across the Bay Area, but the interaction of these two clouds meant that individual exposomes were often strikingly different.
Snyder’s exposome, for instance, showed relatively low exposure to pyridine, apparently because the paint in his house lacks this common antifungal additive. Thus, Snyder also lives with a rich fungal flora as a result. By comparing the timing of a mild allergy with his exposome results, he also discovered that the pollen causing his symptoms came not from the pine trees in his yard, as he had suspected, but from a eucalyptus.
Beyond human health, says the study’s first author Chao Jiang, a postdoctoral researcher in Snyder’s lab, the exposome monitor “is a great tool for studying the evolution and ecology of the things living around us, for exploring the diversity of life.” It can even provide insights into our own hidden emotions. Many of the study’s samples, for instance, contained geosmin—the chemical compound responsible for the earthy smell that causes us to inhale deeply, and often with a hint of joy, when rain comes after a drought. “It’s not just about things that can kill us,” Jiang says.
David Relman, a Stanford microbiologist who was not involved in the study, described the new research as “fascinating for the set of questions it raises, more so than for anything it might answer.” Environmental health studies often cannot explain the puzzling variability in individual health among people living in the same area and exposed to the same pollutants, he says. The conventional explanation is a kind of epidemiological shrug: Maybe some people experienced a different dosage? Maybe they were genetically predisposed to be vulnerable?
Exposome monitoring, on the other hand, “allows for massively parallel collection of data,” Relman says. “And that means we can look for combinations of environmental factors that are present at the same place or time, and that might have synergistic or even antagonistic effects for human health.” Imagine a group of people is exposed to the same toxic chemical, he suggests. It might turn out that severe symptoms occur only in those victims also exposed to a certain fungal spore at the same time, for example, and not in people who do not encounter that particular fungus.
“The technology is great. The ability to collect both microbial and chemical components you are exposed to is brilliant,” adds University of Chicago microbiome researcher Jack Gilbert, who also was not involved in the study. “I want the technology. I want it for my own research.”
But Gilbert adds that “the general design of the study was not ideal,” mainly because he believes there were too few test subjects and too few replications in comparable circumstances. A better design, he suggests, might involve comparing the daily exposomes over a month for 10 or 20 health care workers in the hospital, versus an equal number based at home. Gilbert adds that Snyder “has been very open about the fact that the amount of data in the study design wasn’t perfect,” largely for budgetary reasons.
Each monitoring device cost $2,700 before modification, according to the study, and testing of samples was even more expensive. But Snyder says that his team now hopes to deploy a miniaturized version of the monitor—this one about the size of a small pocket matchbox—on 1,000 test subjects a year from now, with the ultimate goal of commercializing a smartwatch version of the exposome monitor.
Snyder adds that he is currently wearing eight different monitoring devices, including three smartwatches, either to collect data or to evaluate new technologies. The first version of the exposome monitor was “a bit clunky,” he admits. “And as they get older they hum more. My wife notices it. There are times when she says, ‘Do you have to have that thing?’” But he adds, in the course of an interview, that it is on his desk—still monitoring as he speaks.